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Pfizer Oncology: ADC Development Overview (2016)

Pfizer Oncology is using its understanding of the biology of cancer to explore a number of antibody-linker-cytotoxin combinations and build proprietary ADC platforms to develop a diverse ADC toolkit. Pfizer scientists strives to advance the frontiers of cancer biology and to translate this knowledge into high-impact medicines for cancer patients.

Pfizer_Int_HQ_NY_USALate-Stage Assets
Gemtuzumab ozogamicin (Mylotarg®) a recombinant, humanized anti-CD33 monoclonal antibody (IgG4 κ antibody hP67.6) covalently attached to the cytotoxic antitumor antibiotic calicheamicin (N-acetyl-γ-calicheamicin) via a bifunctional linker (4-(4-acetylphenoxy)butanoic acid). The drug has been studied in acute myeloid leukemia (AML), a bone marrow cancer.

Inotuzumab ozogamicin is an investigational ADC comprised of a CD22-directed mAb linked to the cytotoxic agent calicheamicin and is being studied in relapsed/refractory acute lymphoblastic leukemia (ALL).

Early-Stage Investigational Assets
In addition to late-state assets, Pfizer is also developing a series of early stage investigational antibody-drug conjugates.  These novel drugs include:

  • PF-06650808 is an anti-NOTCH3 ADC that is comprised of a humanized antibody targeting the NOTCH3 receptor, which is overexpressed in a number of human cancers, linked to an auristatin-based cytotoxic agent. In a Phase I study (NCT02129205) designed to assess the safety and tolerability at increasing dose levels of PF-06650808 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase II dose, the trial drug showed an acceptable safety profile in patients with advanced malignancies, including triple negative breast cancer (TNBC), ovarian cancer and non-small cell lung cancer. [1] PF- 06650808 also showed early indication of anti-tumor activity in an unselected patient population. [2]
  • PF-06647020 is an anti-PTK7 ADC that is comprised of a humanized monoclonal antibody directed against PTK7, which is also expressed in many tumor types, linked to an auristatin microtubule inhibitor payload. In a Phase I study (NCT02222922) designed to assess the safety and tolerability at increasing dose levels of PF-06647020 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase II dose, the trial drug showed an acceptable safety profile in patients with advanced malignancies, including triple negative breast cancer (TNBC), ovarian cancer and non-small cell lung cancer. PF-06647020 also showed early indication of anti-tumor activity in an unselected patient population. [3][4]
  • PF-06647263 is an anti-EFNA4 ADC that is comprised of a humanized monoclonal antibody against Ephrin-A4 (EFNA4), which is overexpressed in a number of human tumors, linked to the cytotoxic agent calicheadmicin. In a Phase I study PF-06647263 (anti-EFNA4) showed an acceptable safety pro le in patients with advanced malignancies, including triple negative breast cancer and ovarian cancer.[5] Results showed early indication of anti-tumor activity in an unselected patient population.[6]

References:
[1] Rosen, L.S., et al. 30LBA A Phase 1 dose escalation, safety, and pharmacokinetic study of PF-06650808, an anti-Notch3 antibody drug conjugate, in adult patients with advanced solid tumors. European Journal of Cancer. DOI: 10.1016/S0959- 8049(16)31948-7.<br>

[2] A Dose Escalation Study of PF-06650808 in Patients With Advanced Solid Tumors (NCT02129205). Online. Clinicattrials.gov. last accesses, July 12, 2016 <br>
[3] Tolcher, A.W., et al. 28LBA A Phase 1 study of PF-06647020, an antibody-drug conjugate targeting PTK7, in patients with advanced solid tumors. European Journal of Cancer. DOI: 10.1016/S0959-8049(16)31946-3.<br>
[4] A Study Of PF-06647020 For Adult Patients With Advanced Solid Tumors (NCT02222922). Online. Clinicaltrials.gov. Last accessed, July 12, 2016<br>
[5] Hong, D.S., et al. First-in-human dose escalation, safety, and PK study of a novel EFNA4-ADC in patients with advanced solid tumors. J Clin Oncol (Meeting Abstracts) 2015: 2520. Online at http://meeting.ascopubs.org/cgi/content/abstract/33/15_ suppl/2520. Accessed April 1, 2015. NCT02078752?term=PF-06647263&rank=1. Last accessed July 12, 2016.<br>
[6] A Study Of PF-06647263 In Patients With Advanced Solid Tumors (NCT02078752). Online. Clinicaltrials.gov. Last accessed July 12, 2016.

 


Last Editorial Review: July 12, 2016

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