A phase 1 trial of the bifunctional EGFR/TGFβ fusion protein BCA101 alone and in combination with pembrolizumab in patients with advanced solid tumors.

• DOI: 10.1200/jco.2022.40.16_suppl.2513
• Publication Date: 2022-06-06T16:03:57Z
• Authors: Philippe L. Bedard; Alberto Hernando-...; Richard D. Carvajal; Van K. Morris; Paul K. Paik; Dan Paul Zandberg; John M. Kaczmar; Liviu Niculescu; David Bohr; Ralf Reiners; Elham Gharakhani; Rachel Salazar; Sanela Bilic; Glenn J. Hanna
• Keywords: Tolerability; Clinical endpoint; Pharmacodynamics

2513 Background: BCA101 is a first-in-class bifunctional fusion protein consisting of an anti-EGFR monoclonal antibody (mAb) and TGFβ receptor 2 extracellular domain (TGFβRII-ECD). Herein, we report the safety, pharmacokinetic (PK), pharmacodynamic (PD), preliminary efficacy data as monotherapy in combination with pembrolizumab among patients (pts) advanced solid tumors refractory to standard therapies. Methods: Pts received single agent (SA) or at escalating doses parallel 3+3 design starting 64 mg intravenously (IV) weekly (qw); 240 IV qw 200 q3w. Primary endpoint: safety tolerability (CTCAE v5.0); dose limiting toxicity (DLT) period: 21 days. Secondary endpoints: overall response rate (ORR), PK/PD profile, progression-free survival (PFS), changes plasma intra-tumoral signaling assessed by SMAD2 phosphorylation. Results: As 08-Feb-2022, 60 pts have (part A). Forty-five (colorectal, n=14; pancreatic, n=7; head neck squamous cell carcinoma [HNSCC], n=6) SA up 1500 weekly. Fifteen subjects (SCC anal canal [SCAC], n=8; HNSCC, n=7) ranging from pembrolizumab. Maximum tolerated has not been reached. Common adverse events (AEs) attributed include rash (70%), fatigue (23%), pruritis epistaxis (17% each); all grade (G)2 less. One DLT was observed 1250 (G3 anemia, hematuria). No drug-related G4 AEs deaths were observed. At cutoff, best arm stable disease (SD) 15/39 (39%) evaluable pts. In combination, partial (PR) 3/11 (27%) (2 SCAC, 1 HNSCC) control (DCR) 9/11 (82%). Two 3 responders on study >4 months; including confirmed PR HNSCC pt anti-PD-1 therapy cetuximab. Saturation EGFR target ≥750 mg. Dose proportional increase Cmax AUC 750-1500 Prolonged neutralization TGFβ1 achieved ≥500 Among paired tumor biopsies (n=23), pSMAD2 reduction 62% Conclusions: well clinically active PD-1 blockade predictable profile. A recommended both part B expansion phase for cutaneous SCC. Clinical trial information: NCT04429542.