KEY TAKEAWAYS
- The phase 1/2 study aims to investigate the safety, tolerability, and early clinical activity of GEN1042 in combination with pembrolizumab ± chemotherapy.
- The primary endpoint is to determine the ORR.
- In this ongoing phase 2b trial, patients with NSCLC and recurrent/metastatic HNSCC are receiving GEN1042 + PEM ± CTX; results will be presented upon trial completion.
GEN1042, a bispecific antibody targeting CD40 and 4-1BB, demonstrated promising activity in the phase 1a dose-escalation of an open-label, multicenter phase 1/2 trial for advanced solid tumors. Preclinical data suggested the potential synergy with PD-(L)1 blockade ± chemotherapy. In the safety run-in, GEN1042 + PEM ± CTX showed tolerability and early clinical activity, particularly in advanced/metastatic head and neck squamous cell carcinoma(HNSCC). Ongoing enrollment is focused on evaluating GEN1042 + PEM + CTX in checkpoint inhibitor (CPI) treatment–naive with non-small cell lung cancer (NSCLC) and HNSCC patients.
Ignacio Melero and his team aim to assess the therapeutic potential of GEN1042 combining with pembrolizumab and chemotherapy. The objective was to assess GEN1042 + PEM + CTX in enhancing antitumor responses in a diverse patient population.
The study performed parallel cohorts for NSCLC and HNSCC patients, administering GEN1042 + PEM ± CTX for NSCLC and GEN1042 + PEM ± cisplatin or carboplatin + 5-fluorouracil for recurrent/metastatic HNSCC. The primary endpoint focused on the objective response rate (ORR) per RECIST v1.1, with secondary endpoints including duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety/tolerability, and pharmacokinetics (PK). Combination therapy expansion cohorts are recruiting internationally, spanning Spain, the US, and Denmark.
The ongoing trial holds promise for advancing the understanding of GEN1042’s role in diverse patient populations, indicating a favorable ORR and secondary endpoints in NSCLC and recurrent/metastatic HNSCC patients. Results are yet to be presented.
The study is sponsored by Genmab
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT04083599
Melero I, et al. (2023).” Safety and Antitumor Activity of GEN1042 in Combination with Pembrolizumab _ Chemotherapy in Solid Tumors: Phase 2b Dose-Expansion Trial in Progress” Presented at ESMO IO 2023 (Abstract 160 TiP).
