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U.S. Food and Drug Administration Rejects Sacituzumab Govitecan

The U.S. Food and Drug Administration (FDA) has rejected sacituzumab govitecan also known as IMMU-132, a novel, investigational, antibody-drug conjugate or ADC consisting of SN-38, the active metabolite of irinotecan, conjugated to a humanized monoclonal antibody targeting trophoblastic antigen-2 (Trop2), which is expressed in approximately 80% to 90% of breast cancers.

In an edition of The Onco’Zine Brief on PRX (Public Radio Exchange), recorded during the Annual Meeting of the American Society of Clinical Oncology (ASCO), held in Chicago, Illinois, June 1 – 5, 2018, Peter Hofland and Sonia Portillo spoke with Michael Pehl, President and Chief Executive Officer of Immunomedics about advancements in the development of targeted anti-cancer drugs such as antibody-drug conjugates. Developing successful antibody-drug conjugates has remained a challenge for several decades. And to date only 4 different antibody-drug conjugates have been approved for the treatment of various forms of cancer. Hofland and Portillo ask Pehl how antibody-drug conjugate can be used for the treatment of advanced or metastatic triple negative breast cancer, a form of breast cancer that occurs in about 10% – 20% of all cases of breast cancer. Hofland and Portillo also spoke with Pehl about Immunomedics submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for a new antibody-body drug conjugate for the treatment of patients with advanced or metastatic triple negative breast cancer who previously received at least two prior therapies for metastatic disease [Click here to listen to the program].
Triple-negative breast cancer
The investigational drug is designed for the treatment of patients with triple-negative breast cancer (TNBC) who have failed at least 2 prior therapies for metastatic disease.

About 15% of all diagnosed breast cancers is triple-negative breast cancer and, according to the American Cancer Society, the an annual incidence of the disease in the United States alone is estimated to be about 40,000 patients, with 20,000 diagnosed with metastatic TNBC, in the United States alone.

Triple-negative breast cancer does not express estrogen, progesterone or the HER2 receptor. As a result, the disease is insensitive to most of the available targeted therapies for breast cancer treatment, including HER2-directed therapies like trastuzumab (Herceptin®; Genentech/Roche), and endocrine therapies such as tamoxifen or the aromatase inhibitors.

Viable treatment
“We believe in sacituzumab govitecan’s potential to be a viable treatment option for these patients,” said Michael Pehl, President and Chief Executive Officer of Immunomedics.

This believe was, in part, based on a Breakthrough Therapy Designation the company received in February 2016 and results from various clinical trials investigating the activity of sacituzumab govitecan in patients with advanced cancers. One of the trials, presented at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO), showed that sacituzumab govitecan, as a single agent demonstrated, had significant clinical activity in heavily pre-treated patients with HR-positive, HER-2-negative metastatic breast cancer and has a predictable and manageable safety profile.

However, regardless of the results of clinical results, on february 17, 2019 Immunimedics confirmed that it has received a Complete Response Letter from the FDA for the Biologics License Application in which the FDA rejected the drugs.

Concern
Although the FDA did not raise concerns about the safety or efficacy of sacituzumab govitecan, the disappointing outcome follows serious manufacturing problems identified in the FDA inspection between August 6 and 14, 2018.

“The issues related to approvability in the Complete Response Letter were exclusively focused on Chemistry, Manufacturing and Control matters and no new clinical or preclinical data need to be generated,” Pehl noted.

This investigation revealed that Immunomedics’s quality control unit at the company’s Morris Plains, New Jersey, drug substance manufacturing facility didn’t have the authority to investigate a February 2018 data integrity breach, which didn’t trigger a deviation. This breach included manipulated bioburden samples, misrepresentation of an integrity test procedure in the batch record, and backdating of batch records, such as dates of analytical results.

According to the FDA, Immunomedics did not give an assurance that samples and batch records from commercial batches it manufactured before the data integrity breach were not impacted by it, and the agency was unable to conduct a proper assessment.

As a result of the problems, the FDA cited Immunomedics for multiple violations. However, according to statements to investors in December 2018 made by the company, the identified problems for which the company has been penalized have been addressed and are now (completely) resolved.

Next steps
“We are going to request a meeting with the FDA as soon as possible to gain a full understanding of the Agency’s requirements and timelines for approval and we will work closely with the FDA,” Pehl said.

“The goal [is to bring] this important medicine to patients as soon as possible,” he concluded.


Last Editorial Review: January 18, 2019

Featured Image: Pink ribbon for the breast cancer awareness. Courtesy: © Fotolia. Used with permission.

Copyright © 2010 – 2019 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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2017 San Antonio Breast Cancer Symposium will Highlight Several Antibody-Drug Conjugates and Other Targeted Therapies

This year’s San Antonio Breast Cancer Symposium (SABCS) is taking place on December 5-9th, 2017, and it is expected to bring in a broad international audience of researchers and physicians to discuss the future of breast cancer research and treatment. Many exciting abstracts and posters will be presented and discussed during the conference, many of which are turning their focus toward precision and targeted therapeutics that have changed the way we look at cancer treatment in the past several decades.

Much of today’s cancer research developments are being made in targeted therapy spaces, such as antibody-drug conjugates or ADCs. At SABCS, the exciting presentations and posters dealing with ADCs, and other targeted therapeutics, are expected to provide invaluable information to physicians and researchers that are dealing with hard-to-treat patient populations that need more potent and better tolerable treatment options than what are currently available. A summary of notable presentations and posters dealing with targeted therapeutics at SABCS can be found here.


For an overview of oral and poster presentations about antibody-drug conjugates (ADCs) to be presented during the annual San Antonio Breast Cancer Symposium, December 5-9, 2017, Click here.


Sacituzumab govitecan (IMMU-132)
A general session at San Antonio breast cancer symposium will focus on Sacituzumab govitecan (IMMU-132), a novel ADC that is being investigated in as >3rd line therapy for patients with relapsed/refractory metastatic triple negative breast cancer (mTNBC). The data from this study will be presented and discussed on Wednesday, December 6th, at 11:00am in Hall 3. (Abstract GS1-07)

Previously, Sacituzumab govitecan was granted Breakthrough Designation based on promising data seen in a phase I/II basket trial for patients with multiple, advanced epithelial cancers. Breakthrough therapy designation is granted in order to expedite the development and review of treatments that may demonstrate substantial benefit over the current available treatments, so patients with serious, life-threatening diseases can have access to them treatments as soon as possible.

The ADC has received FDA Fast Track designation for the treatment of patients with triple-negative breast cancer, small-cell and non-small-cell lung cancers, and has also been designated an orphan drug for the treatment of patients with small-cell lung or pancreatic cancer in the U.S., and for the treatment of patients with pancreatic cancer in the European Union. [1] Now, Sacituzumab govitecan has been evaluated for use as a single agent for patients with metastatic triple negative breast cancer who have no other treatment options to turn to.

Metastatic triple-negative breast cancer is an aggressive breast cancer type that currently has very limited treatment options.  After the first line therapy, median overall survival for this disease is 6-13 months, and median progression free survival is typically 3-4 months. [2]

Sacituzumab govitecan targets Trop-2, which is expressed in over 90% of triple negative breast cancer, as well as most epithelial cancers, and delivers SN-38, the active metabolite of irinotecan. In the study that will be discussed at SABCS, 110 metastatic triple negative breast cancer patients saw an overall response rate of 34%, a clinical benefit rate of 46% and a progression free survival of 7.6 months. These promising results have led to the ADC’s submission for consideration of accelerated approval.

A randomized global confirmatory phase III trial using Sacituzumab govitecan is currently underway, and the drug is also being evaluated for use in combination with other drugs in triple negative breast cancer and other breast cancer subsets. To learn more about sacituzumab govitecan, and to follow ongoing clinical trials, click here.[3]

DS-8201a
Later in the week at SABCS, researchers at Daiichi Sankyo will take part in a poster discussion session,  where attendees will learn about the latest findings from an ongoing phase I study of DS-8201a, an ADC under investigation in HER2 breast cancers. DS-8201 uses a novel linker to deliver a topoisomerase I inhibitor, and has a high drug to antibody ratio of (8:1).

In pre-clinical studies, DS-8201 has shown efficacy when used in adotrastuzumab emtansine (T-DM1) resistant HER2 breast cancer, as well as breast cancer that is low in HER2 expression. Now, researchers are focused on a current phase I trial in patients with breast cancer, gastric cancer, and other HER2 expressing tumors. The breast cancer patient cohort will be the focus of the poster discussion on Thursday, December 7th, at 7am in the Stars st Night Ballrooom 1 & 2. (Abstract #1094)

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [4]

In the current trial (NCT02564900), 146 patients are being treated in two phases, a dose escalation part 1, and a dose expansion part 2. Part 2 of this study involved 46 patients with breast cancer that have received an average of five prior regimens in the metastatic setting. Since these patients are in the metastatic stage and significantly pre-treated, targeted therapeutics like DS-8201a become extremely important, as they are left with little to no treatment options.

DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer (NCT02564900)

The available results have shown that DS-8201a is well-tolerated and has significant activity for patients that were pre-treated with T-DM1/ pertuzumab, as well as in patients with low expressing HER2 breast cancer. For these patients, an overall response rate of 41% was observed. In a cohort of patients had received prior T-DM1, treatment with DS-8201a achieved a higher Overall Response Rate (ORR) of 41% compared to the reported response these patients had to their prior T-DM1 treatment with an ORR of 23%. In the subset of 24 pts from cohort 2a who had received prior treatment with pertuzumab and T-DM1, the confirmed ORR was 44%. [5]

“The initiation of this Phase II study represents an important next step to rapidly advance the development of DS-8201, as we will obtain a better understanding of how the smart delivery of chemotherapy directly to targeted cancer cells may help patients with HER2-expressing metastatic breast cancer,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo.

Future of Breast Cancer Research 
In addition to the discussions taking place over antibody-drug conjugates at this year’s San Antonio Breast Cancer Symposium, there are numerous posters that cover other targets therapeutics being developed and evaluated. The San Antonio Breast Cancer Symposium is designed to provide state-of-the-art information on the latest therapeutic options and challenges being researched in breast cancer and pre-malignant breast disease, to an international audience of  physicians and researchers.

Targeted therapeutics are undoubtedly making a strong appearance at this year’s meeting, and are expected to continue to revolutionize the way we treat breast cancer. A complete summary of the other exiting posters in the area of targeted therapeutics can be found here.


Last Editorial Review: November 29, 2017
Last update: November 5, 2017

Featured Image: Women and the power to fight breast cancer Courtesy: © 2017. Fotolia. Used with permission.

Copyright © 2017 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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Interim Phase II Results with Sacituzumab Govitecan in Pretreated Metastatic Urothelial Cancer Shows Confirmed Objective Response Rate (ORR) of 34%

Results from an interim Phase II study with sacituzumab govitecan (IMMU-132) shows that the investigational agent is active in patients with metastatic urothelial cancer (mUC) who have relapsed or are refractory to chemotherapies and immune checkpoint inhibitors or IOs.

Metastatic or unresectable disease is identified in approximately 20% of patients presenting with invasive urothelial cancer. [1] This makes the disease the sixth most common cancer in the United States after lung cancer, prostate cancer, breast cancer, colon cancer, and lymphoma. According to the American Cancer Society, the estimated number of new cases in 2017 is 79.030 and deaths from bladder cancer will reach 16,870. [2]


The results [sacituzumab govitecan] in patients relapsed or refractory to both chemotherapy and therapy with immune checkpoint inhibitors are particularly encouraging, since few options are available for these patients after they become refractory…


ESMO 2017
“The results in patients relapsed or refractory to both chemotherapy and IO therapies are particularly encouraging, since few options are available after they become refractory,” noted Scott T. Tagawa, the Richard A. Stratton Associate Professor in Hematology and Oncology, and an Associate Professor of Clinical Medicine and of Clinical Urology at Weill Cornell Medicine, who presented the results at the ESMO 2017 Congress held September 8 – 12, 2017 in Madrid, Spain.

Despite the fact that five IOs have been approved in the U.S. for patients with advanced bladder cancer following platinum chemotherapy, only about 15% to 25% of patients respond to the new treatments. I believe sacituzumab govitecan has the potential to become a second or later line treatment to platinum- or IO-based therapy,” Tagawa added. [2]

In the single-arm Phase II study with sacituzumab govitecan, the confirmed Objective Response Rate (ORR) among forty-one intention-to-treat patients was 34% (14/41), including two confirmed Complete Responses (CRs) and twelve confirmed Partial Responses (PRs). While eight of the fourteen responders are ongoing and are still receiving treatment, including four long-term responses greater than 1 year and two currently ongoing at 15 and 22 months, the median Duration of Response (DOR) at the time of data cutoff was 12.6 months (95% confidence interval [CI], 7.5 to 12.9 months).

Median PFS at 80% data maturity was 7.1 months (95% CI, 5.0 to 10.7 months).

The enrolled cohort included fourteen patients who progressed after prior IO therapy, eleven of whom received IMMU-132 as the fourth or later line of therapies.

Despite the late-stage setting, the confirmed ORR in this subset of patients was 29% (4/14), with median PFS of 5.4 months (95% CI, 1.9 to 7.2 months) but median OS was not met.

All four responders in this subgroup had three or more prior therapies before being treated with sacituzumab govitecan.

“In light of these favorable interim results with sacituzumab govitecan in metastatic urothelial cancer, we will approach the regulatory authorities to discuss the appropriate path forward in this disease with continued unmet medical need,” concluded Behzad Aghazadeh, Chairman of the Board of Immunomedics.

A total of 41 patients with mUC were enrolled into this open-label multicenter study to receive 10 mg/kg of sacituzumab govitecan on days 1 and 8 of 3-week cycles. Median number of doses received was 3 (range, 1-6). Despite repeated dosing, grade 3 or higher adverse events were limited to neutropenia (39%), anemia (10%), diarrhea (7%), and fatigue (7%).

Tagawa has served as a consultant to and receives research funding from Immunomedics.


Last Editorial Review: September 11, 2017

Featured Image: ESMO 2017 | Special Seassion Clinical Practice Demands. Courtesy: © 2017. European Society of Medical Oncology | ESMO. Used with permission.

Copyright © 2017 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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Sacituzumab govitecan (IMMU-132) Demonstrates Therapeutic Potential in the Treatment of Metastatic Solid Cancers

Two prominent cancer journals have published phase II clinical trial results with sacituzumab govitecan (IMMU-132; Immunomedics) in a total of 104 patients with lung cancer, including advanced small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) patients who relapsed after, or were refractory to, prior treatment with standard chemotherapy or immune checkpoint inhibitors.

Lung cancer is the most prevalent cancer worldwide; 1.8 million patients were diagnosed in 2012. It is also the leading cause of cancer deaths, taking 1.6 million lives annually. The vast majority of lung cancer cases (85%) comprise the NSCLC type, which has had a median life expectancy of 10 months when standard chemotherapy is used. With the introduction of immune checkpoint inhibitors, median survival has increased to almost 15 months when at least 50% of cells were positive for PD-L1.

Pembrolizumab (Keytruda®; Merck & Co) was reported to be more effective than chemotherapy in the frontline setting of patients with metastatic NSCLC at high levels of PD-L1 positivity (progression-free survival 10.3 months vs. 6.0 months for those given platinum-based chemotherapy), but this population only constituted about one-quarter of metastatic NSCLC patients.

In pretreated patients with metastatic NSCLC, the objective response rates for the immune checkpoint inhibitors generally range from 14% to 20%.

Aggressive nature
SCLC comprises approximately 15% of all lung cancers, and has the worst prognosis. This is because of its highly aggressive nature, with about two-thirds of patients already having metastatic disease at diagnosis. While palliative first-line therapy of stage IV SCLC (mSCLC) has a high initial response rate of 60% to 75%, the outcome is poor, with a median progression-free survival of only 5.5 months and a median overall survival of <10 months with platinum-based chemotherapy. Responses to second-line therapy have been poorer, such as <10%, with a median survival of only 4 to 5 months following second- or third-line chemotherapy.

Unfortunately, those patients with platinum-resistant mSCLC (i.e., response duration <3 months) fare even worse.

In the United States, the only approved drug in this second-line setting of chemosensitive patients (duration of response exceeding 3 months), since 1998, is topotecan.  This agent, which is reasonably well tolerated, is indicated for recurrent patients who were sensitive to frontline chemotherapy with platinum-containing regimens.[1]

Topotecan, a water-soluble analog, originates from a family of chemotherapeutic agents, including the parent drug Camptothecin, a plant alkaloid extract derived from the oriental tree Camptothecan acuminate, that inhibit the DNA topoisomerase I enzyme, which is responsible for relaxing a supercoiled DNA helix during DNA synthesis. The agent inhibits the religation step of the enzymatic reaction by stabilizing the DNA enzyme complex.  Following this step, it causes accumulation of persistent single strand DNA breaks.

Although is Topotecan the only approved drug,  irinotecan, taxanes, vinorelbine, gemcitabine, and pemetrexed are given frequently to patients with chemosensitive recurrent disease. Even when patients respond to second-line therapies, there is usually no improved survival. Immune checkpoint inhibitors have not gained a role in the management of mSCLC.

Sacituzumab govitecan and Small-cell Lung Cancer
A study advanced small-cell lung cancer published online in Clinical Cancer Research. In this article the authors [2] evaluated sacituzumab govitecan, a second-generation antibody-drug conjugate or ADC, composed of the humanized anti-Trop-2 antibody linked to SN-38, a payload of the active metabolite of irinotecan with a drug-to-antibody ratio (DAR) of 7.6.

Irinotecan and SN-38 inhibit the nuclear enzyme, topoisomerase- 1, resulting in double-strand DNA breaks and death of the affected cells. However, SN-38 is about 1,000- fold more potent than its parental prodrug, irinotecan.

Because SN-38 is delivered selectively by the anti-Trop-2 antibody, it is believed this toxicity is selective for cancer cells having higher levels of Trop-2 than normal cells. This results in a selective targeting and killing of cancer cells having Trop-2, which includes a large number of cancer types.

Because of the way SN-38 is attached to the cancer-targeting antibody, sacituzumab therapy avoids the debilitating diarrhea caused by irinotecan therapy. However, like irinotecan, the major adverse effect is neutropenia, which is manageable either by reducing or delaying therapy, or treating the patient with a drug that stimulates production of neutrophils.

The study published in Clinical Cancer Research  included 50 patients with small-cell lung cancer with metastatic (stage IV) disease who had a median of 2 prior therapies.

The authors noted:

  • Ninety-two percent of the patients evaluated for expression of the target for sacituzumab govitecan, Trop-2, had elevated levels in their archived tumor specimens.
  • Patients given repeated treatment cycles had manageable toxicity, mostly Grade >3 neutropenia (34%), and 60% of those patients experienced tumor shrinkage from baseline CT measurements.
  • The objective response rate was 17% at the optimal dose schedule; the median duration of response and overall survival were 5.7 and 7.5 months, respectively.
  • Activity was observed in patients who were chemosensitive or chemoresistant to frontline chemotherapy, in patients who failed second-line topotecan, and in a subset who relapsed after immune checkpoint inhibitor therapy.

“In contrast, to topotecan, sacituzumab govitecan showed activity in patients who were either responsive or refractive to frontline therapy, and also to those who relapsed to topotecan. A randomized, controlled trial comparing these two agents in second-line therapy, as well as sacituzumab in the frontline setting, should be undertaken,” noted Jhanelle Gray, MD, of the Moffitt Cancer Center, Tampa, FL, the article’s first author.

Promising new therapeutic candidate
“Sacituzumab govitecan represents a promising new therapeutic candidate for advanced mSCLC, a very lethal cancer with a five-year survival rate of only 6 percent,” commented David M. Goldenberg, Immunomedics’ founder.

“Importantly, this candidate potentially could be the first new therapeutic approved for the treatment of metastatic (stage IV) small-cell lung cancer (mSCLC) in twenty years,” he added.

Sacituzumab govitecan and Non-small Cell Lung Cancer
In the second article published online on May 26, 2017, in the Journal of Clinical Oncology, the authors [3] reported the results of the phase II, multicenter trial of 54 heavily-pretreated patients with metastatic NSCLC who received either 8 or 10 mg/kg sacituzumab govitecan on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR). Progression- free survival (PFS) and overall survival (OS) were secondary endpoints.

  • Some of the key findings reported in this article included:
    In the response-assessable study population (N = 47), which had a median of 3 prior therapies (range, 2-7), 67% of patients showed a shrinkage from baseline CT measurements.
  • The confirmed objective response rate was 19.1%, the median response duration 6.0 months (95% CI, 4.8, 8.3), and the clinical benefit rate (CR+PR+SD>4 months) was 43%. Responses occurred with a median onset of 3.8 months, including patients who had relapsed or progressed after immune checkpoint inhibitor therapy.
  • Median intention-to-treat (ITT) PFS was 5.2 months (95% CI, 3.2, 7.1), and median ITT OS was 9.5 months (95% CI, 5.9, 16.7).
  • Grade 3 or higher adverse events included neutropenia (28%), diarrhea (7%), nausea (7%), fatigue (6%), and febrile neutropenia (4%).
  • Over 90% of 26 assessable archival tumor specimens were highly positive for Trop-2 by immunohistochemistry.

“In a heavily pretreated population like this, the results with sacituzumab govitecan are quite encouraging, suggesting further trials both alone and in combination with other drugs, potentially including immunotherapy, should be strongly considered,” D. Ross Camidge, Director of Thoracic Oncology at the University of Colorado Cancer Center and senior author of this study, explained

“Non-small-cell lung cancer patients will always benefit from additional therapeutic choices, and while immunotherapy and oncogene targeted therapy have certainly revolutionized the treatment for subsets of the disease, the use of ‘smarter’ chemotherapy in the form of an effective antibody-drug conjugate such as sacituzumab govitecan may well be the next major advance we see,” Camidge added.

More promising results
“These promising results in two lung cancer indications, comprising the major cancer killers, attest to the breadth of the therapeutic potential for IMMU-132 in the treatment of metastatic solid cancers. Our principal focus is to seek accelerated approval for this ADC in patients with advanced, heavily-pretreated triple-negative breast cancer (TNBC), for which there is no approved therapy and significant patient unmet need,” noted Behzad Aghazadeh, MD, Chairman of the Board of Immunomedics.

“We have also reported that sacituzumab govitecan, in addition to TNBC, SCLC, and NSCLC, is active in patients with metastatic urothelial cancers, where we hope to update results at a future medical meeting, so we now know it is active in at least four different major solid cancers, Aghazadeh concluded.


Last Editorial Review: July 11, 2017

Featured Image: Lung Cancer Courtesy: © 2017. Fotolia Used with permission.

Copyright © 2017 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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Seattle Genetics and Immunomedics Terminate License Agreement for Sacituzumab Govitecan

Seattle Genetics and Immunomedics today confirmed that they have terminated their Exclusive Global Licensing Agreement for sacituzumab govitecan (IMMU-132), Immunomedics breakthrough therapy candidate to treat metastatic triple-negative breast cancer (mTNBC), and settle the related litigation.

The license agreement had not yet closed due to legal action brought by an Immunomedics stockholder challenging the transaction. The termination and settlement remain subject to court approval.

“The Immunomedics transaction would have effectively utilized our substantial expertise in antibody-drug conjugate (ADC) development to advance IMMU-132 for patients in need,” explained Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics.

“However, due to significant delays and lack of progress towards closing the deal, we are turning our full attention and resources to our promising pipeline and the substantial opportunities in front of us, including the upcoming topline data readout from the ECHELON-1 trial and ongoing or planned pivotal trials of vadastuximab talirine (SGN-CD33A) and enfortumab vedotin (ASG-22ME).”

Termination
Effective upon the termination of the license, Seattle Genetics and Immunomedics have agreed to fully settle, resolve and release each other from all disputes, claims and liabilities. Seattle Genetics will maintain its existing equity investment in Immunomedics granted as part of the licensing agreement, including 3.0 million shares of Immunomedics common stock and a warrant to purchase an additional 8.7 million shares at US $4.90 per share exercisable until December 31, 2017.

New strategic plan
Immunomedics also announced additional business and leadership updates and outlined a new strategic plan to drive long-term value for stockholders. The company has raised $125 million in gross proceeds in a private placement of its Series A-1 Convertible Preferred Stock with institutional investors, and has taken a series of steps to drive positive organizational and operational changes.

Focus on IMMU-132
“[These] significant developments [create a] new level of clarity regarding the progress… and the future direction of the company,” noted Behzad Aghazadeh, Chairman of the Board of Immunomedics.

“After conducting a full multi-faceted review of the organizational, operational, and clinical and regulatory capabilities, we are confident that Immunomedics can fully execute on a strategic plan over the next several years to become a recognized leader in the field of antibody-drug conjugates. We now have the financial ability to fully focus on taking the steps to ensure the company has the right leadership, organizational structure and resources necessary to bring IMMU-132 to market and achieve our long-term objectives. The enthusiastic reception from institutional investors to invest in Immunomedics and IMMU-132 reflects the value the company is poised to deliver to patients, employees and stockholders,” Aghazadeh added.

Newly elected Board of Directors
The newly elected Immunomedics Board of Directors has conducted a multifaceted review of the Company with initial emphasis on IMMU-132 in mTNBC, which had received Breakthrough Therapy Designation for this indication from the U.S. Food and Drug Administration (FDA) in February 2016.

As part of this review, work has focused on the organizational, operational, and clinical and regulatory capabilities, with each being led by highly credentialed independent consultants with specific relevant expertise. These efforts have resulted in an updated timeline for the execution of delivering IMMU-132 to market, with the Immunomedics now targeting the submission of a BLA for IMMU-132 for approval in mTNBC between late fourth quarter 2017 and first quarter 2018, subject to FDA input on the acceptance of the CMC filing plan.

The review confirmed that the data generated in the ongoing 100-patient phase II study of IMMU-132 in 3rd line TNBC, which was fully enrolled in December 2016, can provide the basis for accelerated approval, subject to review by the FDA.

Furthermore, this review has led to detailed filing and manufacturing plans. Alongside the immediate focus on preparations for a BLA filing, Immunimedics will proceed with the final selection of a CRO to launch the confirmatory phase III study with the expectation of first patient enrolled in late Q3 2017, as well as executing on a manufacturing plan to build commercial inventory in preparation for a potential launch in the U.S. in 2018.

Aghazadeh explained that over the course of the upcoming months, the scope of the ongoing strategic review will expand with the goal of executing on the following key initiatives, including developing plans for IMMU-132 beyond mTNBC, explore strategic opportunities for IMMU-132 with regional partners and
execute an orderly management succession plan.

Leadership Transition
Immunomedics also announced that effective upon the execution of a settlement agreement, Cynthia L. Sullivan will be stepping down from all director and officer positions, including her role as president and chief executive officer. Michael R. Garone, the current chief financial officer of Immunomedics, will then assume the role of interim CEO.

“It has been a pleasure to lead Immunomedics to this pivotal stage in its growth,” commented Sullivan. “I am confident that the board and leadership team will continue the work of bringing IMMU-132 to patients as soon as possible.”

In addition, David M. Goldenberg, PhD, Immunomedics founder, is stepping down from all officer positions with the Company, including as chief scientific officer and chief patent officer, effective upon the execution of the settlement agreement. Goldenberg will continue to serve as a director on Immunomedics’ Board.

Litigation
In addition to the resolution of its claims against Seattle Genetics, Immunomedics entered into a binding agreement with Goldenberg, Sullivan, Markison and venBio, that will be subject to court approval. If approved, both the Federal Action [1] as well as the 225 Action [2] will be dismissed.

On Thursday (May 4, 2017) the Court of Chancery entered an order lifting the provisions of the Status Quo Order, and confirming that the Status Quo Board is the lawful Board of the Company.  If approved, the  Settlement Agreement will include a mutual release of all claims that were or could have been asserted in the 225 Action. The Federal Action challenging the annual meeting will be dismissed.

Regarding the venBio Action [3], individual defendants Goldenberg, Sullivan and Markison will be released from all claims made by venBio.

“Today’s announcements collectively represent an important milestone in the next phase of Immunomedics, and while there is significant work ahead, the Board looks forward to continuing to drive value for all stakeholders. The Company has a strong pipeline that we look forward to evaluating and intend to leverage to maximize the value for stockholders. We will be providing additional updates, including with our quarterly earnings release, as appropriate in the coming weeks and months,” Aghazadeh explained.


Last Editorial Review: May 5, 2017

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Sacituzumab Govitecan Show Promising Results in Patients with Advanced Triple-negative Breast Cancer

A clinical trial of an antibody-drug conjugate that combines the active portion of a chemotherapy drug with an antibody targeting a molecule expressed on tumor cells appears promising for the treatment of metastatic triple-negative breast cancer (TNBC).

Results from a phase II clinical trial of sacituzumab govitecan – also called IMMU-132, an investigational drug being developed by Immunomedics – were published online in the Journal of Clinical Oncology. [1]

“This approach may represent a new therapy paradigm for this difficult-to-treat disease, which is typically associated with an aggressive tumor biology and poor survival,” says Aditya Bardia, MD, MPH, of the Massachusetts General Hospital (MGH) Cancer Center, lead and corresponding author of the JCO report.

Triple-negative breast cancer
Triple-negative breast cancers – tumors that do not have estrogen or progesterone receptors and do not overexpress HER2 – are aggressive tumors, often affecting younger patients and African Americans.

Chemotherapy is the standard treatment option, but only produces a response in 15 to 20% of patients with metastatic disease. Responses that are achieved seldom persist, and the average survival is 10 to 13 months. Trop-2 is a molecule overexpressed in several tumors that have poor progress, including most triple-negative breast cancers, making it an attractive target for anti-cancer therapy.

A new approach
Sacituzumab govitecan combines an antibody targeting Trop-2 with SN-38, the active metabolite of the chemotherapy drug irinotecan, the use of which is limited because of its significant gastrointestinal side effects.

Animal studies of this antibody-drug conjugate – which can deliver a larger dose of SN-38 directly to tumor cells with little effect on normal tissues – have shown high potency against implanted tumors, effects that were even stronger in combination with other breast cancer drugs, and a phase I clinical trial also had promising results.

Earlier, sacituzumab govitecan has received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with triple-negative breast cancer who have failed prior therapies for metastatic disease.

Trial
The JCO paper reports on 69 patients with metastatic triple-negative breast cancer who enrolled in a larger trial testing sacituzumab govitecan in a number of Trop-2-expressing solid tumors. All the patients in this study had been treated with at least one previous therapy and most had received several – the average was five – and had extensive metastatic disease.

The study protocol called for intravenous administration of the drug on day 1 and day 8 of repeated 21-day cycles. Treatment continued as long as participants appeared to benefit and was halted if the tumor progressed, if there were significant side effects, or if the patient or treating physician chose to discontinue.

By the study cutoff in August 2016, 21 participants had achieved a response of a 30% or greater reduction in tumor size – two achieving complete remission – and nine of those continued treatment for at least 12 months. Almost 70% of participants had some measurable tumor shrinkage. The responses appeared less than two months after treatment began and lasted an average of almost nine months, with three lasting around 20 months. Overall survival averaged 16.6 months. Side effects such as nausea, hair loss and a drop in white blood cells were generally moderate and manageable with appropriate supportive therapy.

Encouraging results
“We saw very encouraging responses that were early and durable in patients who had been heavily pre-treated with an average of five prior therapies since diagnosis. The major toxicities of this drug are manageable, which means it can be given repeatedly,” says Bardia, who is an assistant professor of Medicine at Harvard Medical School.

“It now needs to be studied in patients with early-stage disease, in combination with other drugs and to treat patients with other forms of breast cancer,” Bardia concluded.


Last Editorial Review: March 14, 2017

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Seattle Genetics to Lead Global Development, Manufacturing and Commercialization of Sacituzumab Govitecan

The global biotechnology company Seattle Genetics earlier today confirmed development and icencing agreement with Immunomedics. Under the terms of the agreement, Seattle Genetics receives exclusive worldwide rights to develop, manufacture and commercialize sacituzumab govitecan, also known as  IMMU-132.

Sacituzumab govitecan is an investiagtional  antibody-drug conjugate or ADC targeted to TROP-2, which is expressed in several solid tumors including cancers of the breast, lung and bladder. The drug is composed of an anti-TROP-2 antibody linked to SN-38, the active metabolite of irinotecan. TROP-2 is a cell-surface receptor that is expressed on several tumors, including cancers of the breast, colon, lung and bladder.

Clinical trials
The investigational drug is in a phase I/II trial for patients with triple negative breast cancer (TNBC), as well as multiple other solid tumors.

In data reported from these phase I/II trial, in 85 evaluable patients with metastatic TNBC, sacituzumab govitecan showed an objective response rate of 29% and a median duration of response of 10.8 months. For all 89 patients in the intent-to-treat population, the estimated median overall survival was 18.8 months. Sacituzumab govitecan was generally well-tolerated. The most common adverse events were nausea, neutropenia, diarrhea, anemia, vomiting and fatigue.

Breakthrough Therapy Designation
In 2016 the drug received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with TNBC who have failed prior therapies for metastatic disease. The regulatory agency has also granted the ADC Fast Track designation for patients with small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC).

In addition, sacituzumab govitecan has been designated an orphan drug by the FDA for the treatment of patients with SCLC or pancreatic cancer and by the European Medicines Agency (EMA) for the treatment of patients with pancreatic cancer.

Data from the phase I/II trial are intended to serve as the basis for a planned Biologics License Application (BLA) submission under the FDA’s accelerated approval regulations.

Clay_Siegall_Seattle_Genetics
Photo 1.0: Clay Siegall, Ph.D., President and Chief Executive Office of Seattle Genetics.

Multi-product oncology company
“This agreement would add a promising late-stage ADC to our pipeline as we continue making progress towards our goal of becoming a global, multi-product oncology company. Sacituzumab govitecan would complement our existing pipeline by providing a potential near-term opportunity to commercialize a second drug in the United States, expand our international capabilities in Europe and elsewhere and extend our efforts in solid tumors,” noted Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics.

“In addition, we believe our expertise in ADCs, including demonstrated success in clinical development, regulatory, manufacturing and commercialization, ideally positions Seattle Genetics to advance this program globally. We look forward to working with Immunomedics to advance this program for patients in need, including those with triple negative breast cancer and other solid tumors,” Siegall added.

“After a long and robust process, we concluded that licensing our lead asset, sacituzumab govitecan, to Seattle Genetics, the leading ADC company, would give us the best opportunity to advance this product on behalf of advanced stage cancer patients,” Cynthia L. Sullivan, President and Chief Executive Officer of Immunomedics explained.

“Sacituzumab govitecan has the potential to drive significant value for patients with multiple types of cancer who are in need of new therapy options, and we look forward to continuing its development with Seattle Genetics,” she added.

Agreement
Upon closing of the transactions contemplated by the development and license agreement, Immunomedics receives an upfront payment of $250 million. In addition, Seattle Genetics pays development, regulatory and sales-dependent milestone payments across multiple indications and geographic regions of up to a total maximum of approximately $1.7 billion, as well as tiered double-digit royalties.

The closing of the transactions contemplated by the development and license agreement is subject to customary conditions, including the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended.

Potential for other partners
In addition, for a limited period of time, Immunomedics has the right to continue discussions with a small number of parties that previously expressed interest in licensing sacituzumab govitecan. If a third party provides Immunomedics with a financially superior licensing offer, Seattle Genetics has the right to match any such offer, and if it decides not to match, Immunomedics has the right to accept the superior offer and terminate the proposed development and license agreement upon payment of a termination fee to Seattle Genetics.

Financial impact
Concurrent with the transaction, Seattle Genetics is purchasing approximately $15 million of common stock, representing a 2.8% stake in Immunomedics. Seattle Genetics has also been granted the right to purchase an additional 8,655,804 shares of common stock at a price of $4.90 per share for a defined period.

The equity purchase and rights are not subject to closing of the development and license agreement.

Seattle Genetics’ 2017 financial guidance provided on and as of February 9, 2017 does not take into account the impact of the transactions contemplated by the development and license agreement or the equity investment in Immunomedics. Seattle Genetics plans to update its 2017 financial guidance after the closing of the transactions contemplated by the development and license agreement.


Last Editorial Review: February 10, 2017

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Antitumor Effect of Sacituzumab Govitecan in Triple-Negative Breast Cancer Can be Enhanced With DNA-Repair Inhibitors

Based on a pre-clinical study, treatment of patients sacituzumab govitecan, also known as  IMMU-132 (Immunomedics), in patients with metastatic triple-negative breast cancer (mTNBC) has the potential to be further improved when combined with agents that inhibit DNA repair pathways both in patients with mutated and wild-type BRCA1/2.

Results from this pre-clinical study were published online in Clinical Cancer Research, which is the official publication of the American Association for Cancer Research (AACR).

“This preclinical study is part of our ongoing strategy to broaden the applicability of this important asset for the treatment of patients with solid cancers and the positive results we have achieved thus far are a testament to the strength of our talented team. The progress we have made affirms our commitment to continued product development,” remarked Cynthia L. Sullivan, Immunomedics’ President and Chief Executive Officer.

IMMU-132 is a first-in-class antibody-drug conjugate or ADC developed by Immunomedics, is a clinical-stage biopharmaceutical company by conjugating the moderately-toxic drug, SN-38, site-specifically and at a high drug-to-antibody ratio (DAR) to a humanized antibody that targets the Trop-2 receptor expressed by many solid cancers. In a single-arm Phase 2 study, this ADC has produced rapid and durable responses in metastatic TNBC patients, with only limited and manageable Grade 3 or 4 toxicity, and has received a Breakthrough Therapy Designation from the FDA in this cancer setting.

Active metabolite of irinotecan
SN-38 is the active metabolite of irinotecan (Camptosar), which is used to treat certain solid cancers as a part of combination therapies. It exerts its cell-killing activity by inhibiting topoisomerase I, an enzyme needed by the cell for normal DNA replication. This inhibition results in breaks in the DNA during replication, leading ultimately to the cell’s death if left unrepaired by the cell. The goal of this preclinical study was to determine whether the DNA-damaging property of IMMU-132 can be augmented by agents that inhibit the repair of DNA.

Poly (adenosine diphosphoribose) polymerase or PARP is a family of enzymes whose primary function is to repair DNA breaks. It is one of several proteins used by cells for this purpose.  PARP inhibitors (PARPi), such as olaparib (AZD-2281; Lynparza®; AstraZeneca) and talazoparib (BMN-673; Medivation) are currently under investigation in cancers whith existing DNA-repair defects (BRCA1 and BRCA2).

BRCA1 and BRCA2 are a pair of genes that encode proteins important in a cell’s ability to repair double-stranded DNA breaks. In cell culture, the cytotoxicity of IMMU-132, when combined with one of three different PARPi’s, olaparib, talazoparib, and rucaparib (AG-014699, PF-01367338; Clovis Oncology), produced synergistic growth inhibition in BRCA1 and BRCA2-defective human TNBC tumor lines.

Furthermore, combining IMMU-132 with these PARPi’s also demonstrated synergy in BRCA1 and BRCA2 wild-type tumor lines in which the DNA-repair pathways are not defective. In mice bearing human TNBC tumors with mutated BRCA1 and BRCA2, a combination of IMMU-132 plus olaparib or talazoparib produced significantly improved antitumor effects and delay in time-to-tumor-progression, compared to monotherapy. Most importantly, in mice bearing tumors that are not defective in DNA repair (BRCA1 and BRCA2 wild-type), the combination of IMMU-132 plus olaparib imparted a significant antitumor effect and survival benefit above that achieved with monotherapy. Noteworthy, this combination was well tolerated, with no substantial changes in hematologic parameters.

“These preclinical results indicate that the combination of PARPi and IMMU-132 could broaden the range of tumors that are usually treated with the former to a TNBC patient population that includes BRCA1/2 wild-type tumors. Given the promising results obtained thus far with IMMU-132 in patients with TNBC, the logical next step is to combine this therapy with PARPi to further improve clinical outcome,” Ms. Sullivan noted.


Treatment Groups N Time-To-Tumor (TTP) Progression
Olaparib Talazoparib
  TTP (days  )   IMMU-132 vs. Control
(P-value)
  Combination vs. Control
(P-value)
  TTP (days)   IMMU-132 vs. Control
(P-value)
  Combination vs. Control
(P-value)
  IMMU-132 + PARPi  10 36.9 ± 8.1 N.A. N.A. 21.8 ± 9.6 N.A. N.A.
IMMU-132 alone 9   17.6 ± 3.9 N.A. <0.0001   7.9 ± 6.6 N.A. 0.0021
PARPi alone 9   9.1 ± 4.8 0.0009 <0.0001   5.9 ± 5.9 0.5099 0.0005
Saline Control 10   7.7 ± 5.0 <0.0001 <0.0001   4.2 ± 1.9 0.0709 0.0001

N = Number of mice per group
N.A. = Not Applicable

Table 1.0: Improved efficacy of IMMU-132 when combined with olaparib or talazoparib in mice bearing TNBC tumors that are deficient in DNA repair.


Last Editorial Review: January 9, 2017
Last Editorial Update: January 11, 2017

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New Patents Awarded for Immunomedics’ Antibody-drug Conjugates Development Program

Earlier this week Immunomedics announced that the United States Patent and Trademark Office (USPTO) has awarded U.S. Patent 9,492,566, the 32nd U.S. patent protecting the use of sacituzumab govitecan (IMMU-132), the lead antibody-drug conjugate (ADC), for the treatment of patients with Trop-2-positive cancers being developed by the company.

In an ongoing Phase II clinical study, sacituzumab govitecan has produced encouraging objective response rates and durable responses in heavily-pretreated patients with metastatic triple- negative breast (TNBC), small-cell and non-small-cell lung, and urothelial cancers.

Hematological malignancies
The promising results in solid cancers have motivated researchers at Immunimedics to expand its antibody-drug conjugate (ADC) program to include hematological malignancies such as non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Using the same CL2A linker and the SN-38 toxic payload, researchers at Immunomedics, developed IMMU-140, the subject of U.S. Patent 9,493,573 issued for additional claims under the patent family, “Dosages of immunoconjugates of antibodies and SN-38 for improved efficacy and decreased toxicity.”

IMMU-140
The parent antibody in IMMU-140 is an anti-HLA-DR IgG4 antibody (IMMU-114) that has demonstrated evidence of treatment responses in more than 50% of assessable patients in a Phase I study in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) without reaching a maximum tolerated dose. At the Annual Meeting of the American Society of Hematology, to be held December 3-6, 2016, Immunomedics will present preclinical results on in vitro and in vivo activity of IMMU-140 in animal models of five ‘liquid cancers‘, NHL, CLL, acute myelocytic and lymphocytic leukemia, and multiple myeloma.

Researchers at Immunomedics have also created another ADC targeting B-cell hematologic malignancies. Protected by the new U.S. Patent 9,493,574 under the same patent family. This new antibody-drug conjugate comprises a humanized anti-CD19 antibody, hA19, conjugated to SN-38.

All three new ADC patents will expire in July 2033.

“We are pleased to receive these new patents, which provide extensive intellectual property protection for our robust ADC program that has the potential to address approximately 90% of all human cancers based on the number of estimated new cases in the U.S., as compiled by the American Cancer Society,” noted  Cynthia L. Sullivan, President and Chief Executive Officer.


Last Editorial Review: November 15, 2016

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Enhancing Activity of Sacituzumab Govitecan in SN-38-Resistant Cancer

Adding an inhibitor of ATP-binding cassette (ABC) transporters to sacituzumab govitecan increased the median survival of mice bearing a SN-38-resistant human gastric cancer cell line. Results from this preclinical study were published in Molecular Cancer Therapeutics.[1]

ATP-binding cassette transporters are ubiquitous membrane proteins.  They are characterized by active ATP-dependent movement of a range of substrates, including ions, lipids, peptides, steroids. Individual subunits are typically made up of two groups of 6TM-spanning domains, with two nucleotide-binding domains (NBD).[2]

Sacituzumab govitecan, being developed by Immunomedics, a clinical-stage biopharmaceutical company developing monoclonal antibody-based products for the targeted treatment of cancer, is a first-in-class antibody-drug conjugate or ADC developed by conjugating the moderately-toxic drug, SN-38, site-specifically and at a high ratio of drug to hRS7, a humanized antibody that targets the Trop-2 receptor expressed by many solid cancers.

Promising results
This novel drug candidate, Immunimedics lead antibody-drug conjugate for solid cancer therapy,  has produced promising therapeutic results in some patients with metastatic solid cancers in an open-label, single arm Phase II study. Based on results from this mid-stage trial, the U.S. Food and Drug Administration (FDA) has granted sacituzumab govitecan Breakthrough Therapy designation for the treatment of patients with triple-negative breast cancer, a disease which is negative for estrogen receptors (ER-), progesterone receptors (PR-), and HER2 (HER2-), who have failed prior therapies for metastatic disease. Following this initial designation, Immunomedics is working with the FDA toward a potential accelerated approval in this disease setting.

Multidrug resistance
A common cause of treatment failure in cancer therapy is multidrug resistance. In general, the occurrence of drug resistance in cancer cells can be intrinsic or acquired, with each type resulting from a variety of factors, such as decreased uptake of soluble drugs, activation of drug-detoxifying systems, modulation or mutation of drug targets, defective apoptosis pathways, and, above all, overexpression of the ABC transporters, which act by expelling drugs from the cell, thereby lowering the amount of drugs inside the cancer cells.

Preclinical Study
The objective of this preclinical study was to explore the use of known inhibitors of ABC transporters for improving the therapeutic efficacy of sacituzumab govitecan by overcoming SN-38-resistance. Human breast and gastric cancer cell lines were first made resistant to SN-38 by continuously exposing them to increased concentrations of SN-38 over a period of approximately 2 years. The two SN-38-resistant cell lines were shown to be 50-fold less responsive to SN-38 than their parental cells.

Restored toxicity
Treatment of both SN-38-resistant human cancer cell lines with known inhibitors of ABC transporters restored toxicity of SN-38. More importantly, when sacituzumab govitecan was combined with YHO-13351, an inhibitor of ABC transporter, in mice bearing SN-38-resistant human gastric cancer cell line, a statistically significant 64% improvement in median survival was achieved in comparison with untreated animals (P = 0.0278). Sacituzumab govitecan alone had a 29% improvement in median survival, while the water-soluble diethylaminoacetate prodrug YHO-13351 showed no effect on its own. Although irinotecan plus YHO-13551 improved the survival of the mice, it did not reach significance (P = 0.0852).

“These in vivo results suggest that suitable inhibitors that are tolerated well by the host animals can overcome ABC resistance and that the resistant tumor lines can become appreciably responsive to IMMU-132 and to a lesser extent to irinotecan,” noted Cynthia L. Sullivan, President and Chief Executive Officer of Immunomedics.

“We are pursuing further work to address the feasibility of preclinical testing for such drug resistance as a predictive bioassay to select patients who should receive ABC-blocking therapy with IMMU-132, in order to enhance the potency of IMMU-132 in cancer cells that are intrinsically or become resistant to SN-38,” Sullivan added.


Last Editorial Review: August 22, 2016

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Copyright © 2016 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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