620P MGC018, an anti-B7-H3 antibody-drug conjugate (ADC), in patients with advanced solid tumors: Preliminary results of phase I cohort expansion

Abstract

MGC018 is an investigational ADC with a duocarmycin payload linked to an anti-B7-H3 monoclonal antibody. B7-H3 is expressed on multiple solid tumors with limited normal tissue expression. It is hypothesized that MGC018 may exert activity against B7-H3-expressing tumors with an acceptable safety profile. Phase I dose escalation was completed with two dose-limiting toxicities: one neutropenia grade 4 and one grade 3 fatigue of 72 hrs. There was 1 confirmed partial response in a melanoma patient, and 5/9 patients with 50% prostate-specific antigen (PSA) reduction in metastatic castration resistant prostate cancer (mCRPC). The cohort expansion characterizes safety and preliminary efficacy with the recommended phase II dose of 3 mg/kg IV every 3 weeks. 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 are eligible for enrollment. Response is evaluated per RECIST v1.1 for all participants. mCRPC tumor response and PSA are evaluated using Prostate Cancer Working Group 2 criteria. The cohort expansion enrolled and dosed 49/80 patients as of May 3, 2021. 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 (≥10%) were neutropenia/neutrophil count decreased, fatigue, asthenia, palmar plantar erythrodysesthesia, and headache. Febrile neutropenia was not reported. Of 13 mCRPC patients with measurable disease, six were not yet evaluable, and seven had first 9-week imaging. Of the seven, 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. Results to date have demonstrated 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. Updated data will be provided.