160TiP Safety and antitumor activity of GEN1042 in combination with pembrolizumab ± chemotherapy in solid tumors: Phase IIb dose-expansion trial in progress

GEN1042 (DuoBody CD40x4-1BB) is a novel, bispecific, agonistic antibody that combines targeting and conditional activation of CD40 and 4-1BB on immune cells to enhance priming and (re)-activation of tumor-specific immunity. In the phase 1a dose-escalation part of this open-label, multicenter phase 1/2 trial (NCT04083599), single-agent GEN1042 showed biologic and early clinical activity with a manageable safety profile in patients with advanced solid tumors. Preclinical and preliminary clinical results suggest that as a bispecific antibody, GEN1042 can leverage conditional CD40 and 4-1BB agonism in combination with PD-(L)1 blockade ± chemotherapy (CTX) to improve the antitumor response. In the safety run-in and expansion cohorts, GEN1042 in combination with pembrolizumab (PEM) ± CTX was generally well tolerated (no dose-limiting toxicities) with encouraging early clinical activity, including complete responses, observed in patients with advanced/metastatic head and neck squamous cell carcinoma (HNSCC) receiving GEN1042 + PEM + CTX (Melero I, et al. ESMO IO 2022). Enrolment into the combination therapy expansion cohorts is continuing, with this abstract focused on the evaluation of GEN1042 + PEM + CTX in checkpoint inhibitor (CPI) treatment–naive patients with non-small cell lung cancer (NSCLC) and HNSCC. The expansion part includes parallel cohorts of patients with NSCLC and HNSCC. Eligible patients with NSCLC will receive GEN1042 + PEM ± CTX. Eligible patients with recurrent/metastatic HNSCC (PD-L1 combined positive score ≥1) will receive GEN1042 + PEM ± cisplatin or carboplatin + 5-fluorouracil. Primary endpoint (phase 2b) is objective response rate per RECIST v1.1. Secondary endpoints are duration of response, disease control rate, progression-free survival, overall survival, safety/tolerability, and pharmacokinetics. Combination therapy expansion cohorts are recruiting across several countries including Spain, US, and Denmark. NCT04083599; Release Date: September 10, 2019. Medical writing and editorial support were provided by Stephanie Phan, PharmD, from Peloton Advantage, an OPEN Health company, Parsippany, NJ, USA. Genmab A/S. Genmab A/S and BioNTech SE.