The 51st ASCO – the Annual Meeting of the American Society of Clinical Oncology, which will take place in the McCormick Place Convention Center in Chicago, Illinois, May 29 – June 2, 2015 is expected attract more than 30,000 oncology professionals from around the world.
This year’s Annual Meeting will focus on the theme of Innovation and Illumination, pointing to the potential for integrating cancer science and health information technology (HIT) to achieve more rapid improvements in patient care. Along with new research, HIT initiatives such as ASCO’s CancerLinQ™ will be featured prominently at the meeting.
Also prominently featured this years are the nearly 100 presentations and abstracts related to antibody-drug conjugates or ADCs. Among these presentations are two oral presentations featuring Immunomedics’ second generation antibody-drug conjugate (ADC) programs for solid cancer therapy. Leading that program is sacituzumab govitecan, an anti-TROP-2 antibody conjugated with SN-38, an active drug from irinotecan. Irinotecan is approved for the treatment of patients with colorectal cancer. Results from a Phase II study of sacituzumab govitecan in patients with advanced lung cancer will be updated in one of the 2 oral presentations. In addition to this oral presentation, results with sacituzumab govitecan in patients with late-stage triple-negative breast and gastrointestinal cancers will be reported in a Poster Discussion and a Poster Sessions, respectively.
Also presented, in the same Oral Abstract Session as sacituzumab govitecan, will be initial results from a Phase II study of labetuzumab govitecan, another SN-38-containing ADC, for patients with metastatic colorectal cancer. One of the presentation will feature a pilot study on TF2, a bispecific antibody, for pretargeted imaging of breast cancer. 
HuMax-TF-ADC and Daratumumab
Genmab A/S announced that data on HuMax-TF-ADC, daratumumab, ofatumumab (Arzerra®; GSK) and HuMax-AXL-ADC will also be presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting. This presentations include the first preliminary clinical data from the Phase I study of HuMax-TF-ADC in solid tumors and comprehensive data from the Phase II study of daratumumab in double refractory multiple myeloma. With the exception of the Phase II daratumumab data, which has been designated as a late breaking abstract by ASCO, the abstracts have been published at the ASCO website.
HuMax-TF-ADC Phase I Data
Preliminary safety and efficacy data from a Phase I dose escalation study of HuMax-TF-ADC to treat multiple solid tumors will be presented in a poster presentation. HuMax-TF-ADC is an antibody-drug conjugate (ADC) composed of a human antibody against tissue factor (TF) conjugated to Seattle Genetics’ clinically validated cytotoxic drug. HuMax-TF-ADC is being developed for the treatment of solid cancers. Based on its high expression on many solid tumors and its rapid internalization, TF is a suitable target for an ADC approach. Genmab is developing HuMax-TF-ADC using Seattle Genetics’ ADC technology under an agreement between the companies.
The data presented includes data for 18 patients participating in this ongoing study. Preliminary data show a manageable safety profile with no dose limiting toxicities at doses of HuMax-TF-ADC of up to 1.8 mg/kg and preliminary evidence of anti-tumor efficacy was observed, including prolonged disease stabilization in an ovarian cancer patient (23 weeks), two castration resistant prostate cancer (CRPC) patients (18 and 36 weeks) and a confirmed partial response (PR) in a patient with cervical cancer. Data from further patients will be included in the poster at the time of the presentation including observed dose limiting toxicities in the 2.2 mg/kg cohort. Part 2 of the study is now be expanded from 30 to 80 patients, bringing the total patients in this study to approximately 110 patients.
Breaking abstracts and presentations also includes an update of daratumumab, a human CD38 monoclonal antibody with broad-spectrum killing activity. The trial drug, which is in clinical development for multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL), targets the CD38 molecule which is highly expressed on the surface of multiple myeloma cells. Daratumumab may also have potential in other cancers on which CD38 is expressed, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell lymphoma. Daratumumab has been granted Breakthrough Therapy Designation from the US FDA. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop and commercialize daratumumab.
During the annual ASCO meeting results from a number of studies will be presented, including results phase II study of daratumumab (DARA) monotherapy in patients with >=3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius, et al) (Late breaking abstract #LBA8512, Oral Presentation, Tuesday, June 2, 11:21AM to 11:33AM CDT), a twin randomized studies of daratumumab (DARA; D) plus standard of care (lenalidomide/dexamethasone or bortezomib/dexamethasone [DRd or DVd]) versus Rd or Vd alone in relapsed or refractory multiple myeloma (MM): 54767414MMY3003 (Pollux, et al) and 54767414MMY3004 (Castor) (Abstract #TPS8609, Poster session, Sunday/May 31, 8:00AM to 11:30AM CDT), A randomized open-label study of bortezomib, melphalan, and prednisone (VMP) versus daratumumab (DARA) plus VMP in patients with previously untreated multiple myeloma (MM) who are ineligible for high-dose therapy: 54767414MMY3007 (Alcyone, et al.)(Abstract #TPS8608/Poster session, Sunday, May 31, 8:00AM to 11:30AM CDT), Assessing clinical response in multiple myeloma (MM) patients treated with monoclonal antibodies (mAbs): Validation of a daratumumab IFE reflex assay (DIRA) to distinguish malignant M-protein from therapeutic antibody (Abstract #8590/Poster session, Sunday, May 31, 8:00AM to 11:30AM CDT), Pre-clinical translational studies of daratumumab in patients with myeloma or AL amyloidosis undergoing autologous hematopoietic stem cell transplantation (SCT) – (Abstract #8587/Poster session, Sunday, May 31, 8:00AM to 11:30AM CDT)
Results of a phase III randomized, controlled study sponsored by Gilead Sciences, evaluating the efficacy and safety of idelalisib (IDELA) in combination with ofatumumab (OFA) for previously treated chronic lymphocytic leukemia (CLL)(Abstract #7023/Poster Session, Sunday, May 31, 8:00AM to 11:30AM) will be presented. Ofatumumab, which is marketed under a co-development and collaboration agreement between Genmab and Novartis, is a human monoclonal antibody that is designed to target the CD20 molecule found on the surface of chronic lymphocytic leukemia (CLL) cells and normal B lymphocytes. In the United States, ofatumumab is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. In the European Union, the drug is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy. In more than 50 countries worldwide, ofatumumabis also indicated as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.
Preclinical efficacy studies using HuMax-Axl-ADC, a novel antibody-drug conjugate targeting Axl-expressing solid cancers (Abstract #3066, Poster session, Saturday, May 30, 8:00AM to 11:30AM). HuMax-AXL-ADC is an antibody-drug conjugate combining a high affinity human monoclonal antibody against AXL with one of Seattle Genetics’ clinically validated cytotoxic drug. AXL is a signaling molecule involved in multiple processes of tumor development and progression. The target molecule is highly expressed on a variety of solid cancers. Genmab is developing HuMax-AXL-ADC using Seattle Genetics’ ADC technology under a license agreement between the companies.
Clinical data presentations at upcoming ASCO annual meeting also include initial findings of ImmunoGen’s mirvetuximab soravtansine (IMGN853) for ovarian cancer and results from the MARIANNE trial with ado-trastuzumab emtansine (Kadcyla®; Genentech/Roche).
Mirvetuximab soravtansine is the first ADC to target folate receptor alpha (FRα), which is highly expressed on many ovarian cancers and on other types of solid tumors. The ASCO presentations will be on the initial findings from the Phase I expansion cohort assessing this ADC as a single agent for the treatment of patients with FRα-positive platinum-resistant ovarian cancer (abstract #5518) and the dose-finding results to date with a weekly dosing schedule compared with a once every three week schedule (abstract #5558).
Two years ago, ImmunoGen presented preliminary phase I results demonstrated for mirvetuximab soravtansine. These preliminary results showed encouraging signs in gynecologic tumors, including 2 partial responses. However, the preliminary data also showed dose limiting ocular toxicities at the higher doses. Immunogen has, since then, been working on identifying a dosing regimen designed to minimizes ocular toxicity by decreasing early exposure levels. Early results of these alternative dosing levels were presented in 2014, however, no efficacy data were disclosed at that time.
This year also expect updated results from the MARIANNE trial which focus on data evaluating three HER2-targeted regimens – ado-trastuzumab emtansine plus pertuzumab (Perjeta®; Genentech/Roche), ado-trastuzumab emtansine alone, and trastuzumab (Herceptin®; Genentech/Roche) plus taxane chemotherapy – in people with previously untreated (first line) advanced HER2-positive breast cancer.
Seattle Genetics’s SGN-33A (Anti-CD33) may enable the optimal targeting of CD33, which has been considered an attractive target for AML for over a decade based on efficacy observed with gemtuzumab ozogamicin (Mylotarg; Pfizer/Wyeth). Although gemtuzumab ozogamicin was withdrawn from the market in 2010, a number of studies have shown a clear clinical benefit.
SGN-33A offers a novel DNA-binding payload (allowing higher potency relatively to currently used tubulin binders) and site-specific conjugation (offering a better safety profile). Preliminary data presented at annual meeting of the American Society of Hematology (ASH) in San Francisco in December 2014 showed clear and dose-dependent activity with a relatively mild safety profile. Complete Response (CR) rates were 27% for the top three doses, with additional 50% of patients experiencing significant reductions in tumor burden. While this data was indeed encouraging, industry experts consider it not (yet) sufficient to understand whether SGN-33A is effective enough to merit further development as mono therapy. Trial updates presented during the ASCO meeting are expected to shed more light in terms of durability of responses and long-term safety profile.
Both Seattle Genetics and ImmunoGen are expected to present multiple updates and new data related to their own programs as well as to their partnered programs. As indicated at the the 2015 PEGS meeting in Boston, Seattle Genetics is expected to have phase I data for its proprietary LIV1 program as well as news and updated news from multiple partnered programs including Pfizer’s anti-5T4 and anti-NOTCH3.
In total, multiple proprietary and collaborator antibody-drug conjugate (ADC) programs will be highlighted in more than 10 sessions at ASCO. Data will be presented covering ABT-414 in patients with advanced solid tumors likely to overexpress the epidermal growth factor receptor (EGFR) (AbbVie; Abstract #2510, poster presentation) as well as Phase I study of ABT-414 mono- or combination therapy with temozolomide (TMZ) in recurrent glioblastoma (GBM) (AbbVie; Abstract #2016, poster presentation). An additional presentation will cover STEAP1 as a predictive biomarker for antibody-drug conjugate (ADC) activity in metastatic castration resistant prostate cancer (mCRPC) (Genentech; Abstract #5029, poster presentation).
Among the ADC related presentations is also a a multivariate analysis of PFS from the AETHERA trial, a phase III study of brentuximab vedotin consolidation after autologous stem cell transplant for HL (Seattle Genetics; Abstract #8519, poster presentation) as well as a phase I trial of brentuximab vedotin in combination with gemcitabine for pediatric and young adult patients with relapsed or refractory Hodgkin lymphoma, a Children’s Oncology Group report (Investigator-sponsored; Abstract # 8544, poster presentation) will be presented on Monday, June 1, 2015. Updated results of a phase II trial of brentuximab vedotin combined with RCHOP in frontline treatment of patients with high-intermediate/high-risk DLBCL (Seattle Genetics; Abstract #8506, oral presentation 11:21 a.m. CT) followed by Quality of life EQ-5D results from the AETHERA trial (Seattle Genetics; Abstract #6568, poster presentation) and brentuximab vedotin plus AVD for non-bulky limited stage classical Hodgkin lymphoma: a phase II trial (Investigator-sponsored; Abstract #8505, oral presentation 11:09 a.m. CT)
Two doses of polatuzumab vedotin (PoV, anti-CD79b antibody-drug conjugate) in patients (pts) with relapsed/refractory (RR) follicular lymphoma (FL): Durable responses and lower dose level (Genentech; Abstract #8503, oral presentation 9:45 a.m. – 12:45 p.m. CT). Finally, data will be presented from a phase I studies of anti-ENPP3 antibody drug conjugates (ADCs) in advanced refractory renal cell carcinomas (RCC) (Agensys; Abstract #2503, oral presentation 8:00 – 11:00 a.m. CT).
At this time, industry experts consider Immunogen’s partnered pipeline slighltly less advanced than the Seattle Genetics program. One reason is that ImmunoGen’s program (unfortunately) to a great degree relies on the (pre-) clinical programs of Novartis and Lilly. Novartis started phase I with for LOP628 (anti-cKIT) in January 2015, their study is currently listed as suspended.
More than 90 abstracts
This years, more than 90 abstracts and presentations include updates and (late breaking) news covering clinical studies involving Antibody-drug conjugates.
One of the featured educational sessions is on Monday, June 1. As part of the “Developmental Therapeutics and Translational Research; Breast Cancer” Track, Francisco J. Esteva, MD, PhD
(NYU Langone Medical Center), Kathy Miller, MD (Indiana University Melvin and Bren Simon Cancer Center) and Beverly A. Teicher, PhD (Chair; National Cancer Institute at the National Institutes of Health) will be leading “Antibody-Drug Conjugates: New Horizons to Maximize Efficacy and Minimize Toxicity.”
While our team has reviewed just a few interesting antibody-drug conjugates, there are many other ADCs which entered the clinical testing phase in 2013-2014. Some of these trials, as shown, are expected to generate interesting preliminary phase I data to be presented at this years ASCO meeting, making this year’s meeting one of the most interesting society meetings covering antibody-drug conjugates.
Last editorial update: May 26, 2015
Photo: The AACR 2015 Annual Meeting. More than 18,000 physicians, researchers, health care professionals, cancer survivors and patient advocates attended the annual meeting at the Pennsylvania Convention Center highlighting the latest findings in all major areas of cancer research from basic through clinical and epidemiological studies. Photo courtesey: ©AACR/Phil McCarten 2015.
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