During the annual meeting of the European Society for Medical Oncology (ESMO) being held October 7 – 11, 2016 in Copenhagen, Denmark, preliminary data for PF-06647020 in advanced solid tumors was presented as part of a Late Breaking Abstract/Poster Discussion Session (Abstract LBA35). 
The study was initially designed as a dose-escalation study to evaluate safety, pharmacokinetics and antitumor activity for patients with advanced solid tumors. A pre-planned expansion for ovarian cancer included 27 patients that received PF-06647020.
Clinical trial data also confirms that the use of PTK7-targeted therapy resulted in a response of approximately 50% in the case of breast cancer and an almost Complete Response (CR) for ovarian cancer. These early-stage results underline the strong efficacy profile of PF-06647020. The early-stage trials have further demonstrated that PF-06647020, given its low toxicity, is well-tolerated with an acceptable safety profile.
To date, 76 patients have been treated with PF-06647020. A total of 60 of which were treated at 2.8 mg/kg once every 3 weeks (Q3W)/cycle in escalating doses from 0.2 – 3.7 mg/kg until progression.
Most adverse events have grade 1-2 with the majority being self-limiting and nor requiring medical intervention. Most commonly (≥10%) reported drug related adverse events included nausea (46%), alopecia (34%), headache (32%), fatigue (30%), neutropenia (26%), vomiting (22%), decreased appetite (17%), myalgia (15%), arthralgia (11%), and diarrhea (11%).
Fourteen patients (18%) experienced Grade ≥3 drug related neutropenia and 3 patients (4%) discontinued due to drug related adverse events.
Twenty-nine recurrent ovarian cancer patients with ECOG Performance Status 0-1 (median age 58.5 yrs [42-77]) were treated at 2.1 mg/kg (1 pt). Twenty-two patients currently evaluable in this heavily pre-treated group of patients with platinum-resistant ovarian cancer, the trial results showed Complete Response (CR) in 1 patient, 5 patients had Partial Response (PR) with Objective Response Rate (ORR) of 27% (95% CI: 13%, 48%), 12 patients (55%) had Stable Disease (SD), and 4 patients (18%) had Progressive Disease. Median duration of treatment was 3 cycles (range 1–13). A total of 10 patients remained on treatment.
The investigational drug targets PTK7, a catalytically inactive protein tyrosine kinase which functions in developmental biology and is over expressed in a variety of human cancers. Exploratory immunohistochemistry staining by a validated assay on archival tumors showed that all ovarian cancer (OVCA) patients in this had PTK7 expression.
PF-06647020 is an anti-PTK7 Antibody-drug Conjugate being developed by Pfizer in collaboration with Stemcentrx (now part of AbbVie). The novel ADC 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 via a cleavable dipeptide linker.
Advanced Solid Tumors
In the phase I study PF-06647020 showed an acceptable safety profile in patients with advanced malignancies, including triple negative breast cancer (TNBC), advanced ovarian cancer and non-small cell lung cancer (NSCLC). PF-06647020 also showed early indication of anti-tumor activity in an unselected patient population. 
In data presented during the ESMO/ECCO meeting in 2015, PF-06647020 showed some responses at doses above 2.1mg/kg in patients with advanced triple negative breast cancer and platinum resistant ovarian cancer. At that time, no dose-limiting toxicities (DLTs) were reported with dose escalation continuing to 3.7mg/kg. 
“Both triple negative breast cancer and platinum resistant ovarian cancer are difficult to treat, and novel approaches are urgently needed,” noted Markus Joerger, MD, attending medical oncologist at the St. Gallen Cancer Centre (Kantonsspital St.Gallen) in St. Gallen, Switzerland, after reviewing the trial results presented at the annual meeting of the European Society for Medical Oncology. “The clinical activity shown with PF-06647020, is indeed encouraging,” he continued.
“Clinically relevant benefits can be confirmed with some novel targeted agents such as PF-06647020 and it is hoped that their early promise will be confirmed in larger studies,” Joerger concluded.
Last Editorial Review: October 14, 2016
Featured Image: Woman Having Chemotherapy With Nurse Using Digital Tablet Courtesy: © Fotolia. Used with permission. Illustration 1.0: Schematic of PF-06647020 an investigational antibody-drug conjugates targeting PTK7. Courtesy: © Pfizer. Used with permission.
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