469PSafety, efficacy, and pharmacokinetic (PK) profile of cosibelimab, an anti‐PD‐L1 antibody, in patients (pts) with advanced cancers

Abstract Background Cosibelimab is a high affinity, fully-human IgG1 monoclonal antibody (mAb), with functional Fc domain capable of inducing ADCC, that directly binds to programmed death ligand-1 (PD-L1) and blocks the PD-L1 interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors. Cosibelimab is being evaluated in a multicenter phase 1 study (NCT03212404) in pts with advanced cancers. We present preliminary safety, efficacy and PK data. Methods Pts were ≥18 years old with advanced cancers and adequate organ function. In dose escalation, pts received cosibelimab administered intravenously at sequential fixed doses of 200 mg, 400 mg, or 800 mg every 2 weeks (q2w) or 1200 mg every 3 weeks (q3w) using a 3 + 3 design. Following dose escalation, multiple tumor-specific expansion cohorts are being enrolled at 800 mg q2w to further evaluate safety and efficacy. Results As of April 23, 2019, 65 pts (47M/18F, median age 64 years) with diverse tumor types received cosibelimab in dose escalation and expansion cohorts. Cosibelimab has demonstrated acceptable tolerability with no dose‐limiting toxicities. Treatment‐related adverse events (AEs) occurred in 32/65 (49%) pts, most commonly rash (n = 9, 14%) and fatigue (n = 6, 9%). Treatment‐related grade ≥3 AEs occurred in 5/65 (8%) pts, all grade 3, and included anemia, asthenia, hypertension, hyponatremia, and high blood pressure (n = 1 [2%] each). Cosibelimab demonstrated linear PK with features consistent with marketed anti-PD-L1 mAbs. Thirty-six pts were response evaluable of which 10/36 (28%) pts achieved a partial response by RECIST 1.1 criteria (including cutaneous squamous cell carcinoma, non-small cell lung cancer, head and neck squamous cell carcinoma and melanoma), 17/36 (47%) pts achieved stable disease, and 24/36 (67%) pts experienced target lesion reductions versus baseline. Forty-two pts remain on treatment (range, 1-17+ mos). Conclusions Cosibelimab has demonstrated a safe and well-tolerated safety profile with evidence of durable anti‐tumor activity in several advanced cancers, and linear PK. Cosibelimab is being further evaluated in multiple tumor-specific expansion cohorts. Updated results will be presented. Clinical trial identification NCT03212404. Legal entity responsible for the study Checkpoint Therapeutics, Inc. Funding Checkpoint Therapeutics, Inc. Disclosure P.R. Clingan: Research grant / Funding (institution): Merck Sharp & Dohme Corp; Research grant / Funding (institution):