PF-06647020, an ADC, comprised of a humanized monoclonal anti-PTK7 antibody, an auristatin, and a cleavable valine-citrulline linker, is being investigated in a Phase I clinical trial in patients (pts) with advanced solid tumors including triple negative breast cancer, non-small cell lung cancer, and OVCA. Here we report safety results and clinical activity in heavily pre-treated or platinum resistant OVCA pts in this ongoing study.
PF-06647020 was administered intravenously to pts with advanced solid tumors once every 3 weeks (Q3W)/cycle in escalating doses from 0.2 - 3.7 mg/kg until progression. In dose expansion, platinum resistant or refractory OVCA pts (unselected for PTK7 expression) received the recommended phase 2 dose (RP2D). Adverse events (AEs) were evaluated by CTCAE v4.03 and best overall response (BOR) was assessed by RECIST v1.1.
As of May 31, 2016, 76 pts have been treated with PF-06647020, 60 of which were treated at 2.8 mg/kg (identified RP2D) Q3W. Most commonly (≥10%) reported drug related AEs for all pts (mainly Grades 1 - 2) were nausea (46%), alopecia (34%), headache (32%), fatigue (30%), neutropenia (26%), vomiting (22%), decreased appetite (17%), myalgia (15%), arthralgia (11%), and diarrhea (11%). Fourteen pts (18%) experienced Grade ≥3 drug related neutropenia and 3 pts (4%) discontinued due to drug related AEs [pruritus (Grade 2) and fatigue (Grades 2 and 3)]. Twenty-nine recurrent OVCA pts with ECOG PS 0-1 (median age 58.5 yrs [42-77]) were treated at RP2D or 2.1 mg/kg (1 pt). Of 22 pts currently evaluable for BOR assessment, 1 pt had CR, 5 pts had PR (4 were platinum resistant) with ORR 27% (95% CI: 13%, 48%), 12 pts (55%) had SD, and 4 pts (18%) had PD. Median duration of treatment is 3 cycles (range 1–13), and 10 pts remain on treatment. Exploratory immunohistochemistry staining by a validated assay on archival tumors showed all OVCA pts had PTK7 expression.
Encouraging clinical responses have been observed in patients with heavily pre-treated or platinum resistant OVCA. PF-06647020 has an acceptable safety profile and is being further developed.
Clinical trial identification
Legal entity responsible for the study
J.C. Sachdev: 1. Pfizer Investigator 2. Previous research funding from Pfizer for an IIT. M. Maitland, M. Sharma, V. Moreno, V. Boni, S. Kummar: 1. Pfizer Investigator. B. Gibson, D. Xuan, T. Joh, E. Powell, A. Jackson-Fisher, M. Damelin, X. Xin: 1. Pfizer employee 2. Pfizer stock owner. A. Tolcher: 1. Pfizer Investigator 2. Past advisory board member - all honoraria paid to START. E. Calvo: 1. Pfizer Investigator.