(UroToday.com) In the on-demand poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Eugene Shenderov presented preliminary results of a phase I cohort expansion testing MGC018, an investigational ADC with a duocarmycin payload linked to an anti-B7-H3 monoclonal antibody, in patients with metastatic castration resistant prostate cancer (mCRPC).
B7-H3 is expressed on many solid tumors but has limited normal tissue expression. Thus, it has been hypothesized that MGC018 may exert activity against B7-H3-expressing tumors with an acceptable safety profile. In an initial phase I dose-escalation, there were two dose-limiting toxicities: one neutropenia grade 4 and one grade 3 fatigue lasting 72 hrs. In this cohort, there was 1 confirmed partial response in a melanoma patient, and five of 9 patients with metastatic castration resistant prostate cancer (mCRPC) had a 50% prostate-specific antigen (PSA) reduction.
The present cohort expansion characterizes safety and preliminary efficacy with the recommended phase II dose of 3 mg/kg IV every 3 weeks. The authors enrolled patients with advanced mCRPC, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), and melanoma. Treatment response is evaluated per RECIST v1.1 for all participants while, for patients with mCRPC, tumor response and PSA are evaluated using Prostate Cancer Working Group 2 criteria.
As of May 3, 2021, the cohort expansion enrolled and dosed 49 of 80 patients including mCRPC (n=26/40), NSCLC (n=16/20), and TNBC (n=7/20).
At least 1 treatment-emergent adverse event occurred in 43 patients (87.7%). The most common of these, occurring at least 10% of the time, were neutropenia/neutrophil count decreased, fatigue, asthenia, palmar plantar erythrodysesthesia, and headache. However, febrile neutropenia was not reported.
In terms of efficacy, of the 13 mCRPC patients with measurable disease, six were not yet evaluable, and seven had first 9-week imaging. Of the seven who were evaluable, four had reductions in target lesion sums of 13%, 21%, 27%, and 35% (unconfirmed partial response); 12 of the 13 remain on treatment. There are 11/22 evaluable patients with ≥50% PSA reduction.
Thus, the authors conclude that MGC018, an investigational ADC with a duocarmycin payload linked to an anti-B7-H3 monoclonal antibody, demonstrates a manageable safety profile with evidence of clinical activity by PSA and tumor responses in mCRPC. Enrollment is ongoing in advanced mCRPC, NSCLC, TNBC, SCCHN, and melanoma.