futuximab/modotuximab (S95026)

P1, N=51, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: Jul 2024 --> Jan 2025

Nivolumab and pembrolizumab are anti-PD-1 antibodies that improve immunosuppression by binding to programmed death-1 (PD-1), leading to an antitumor effect...Sym004 and amivantamab are antibodies that target the epidermal growth factor receptor and have demonstrated efficacy in the treatment of other tumors in recent phase I studies. Furthermore, clinical trials on antibody-drug conjugates such as enfortumab vedotin and DS-7300 for solid tumors are currently ongoing. The standard first-line treatments for patients with advanced ESCC contain ICIs. Therefore, drugs with different mechanisms of action that can overcome resistance to ICIs are needed as second-line or later-line treatments to improve clinical outcomes in these patients.

P1, N=51, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: Feb 2024 --> Jul 2024

P1, N=51, Active, not recruiting, Institut de Recherches Internationales Servier | Recruiting --> Active, not recruiting

P1, N=41, Recruiting, Institut de Recherches Internationales Servier | Phase classification: P1a/1b --> P1

P3, N=7, Terminated, Institut de Recherches Internationales Servier | N=500 --> 7 | Trial completion date: Oct 2026 --> Jun 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2026 --> Jun 2023; Decision based on strategic reasons related to limited development options left in metastatic colorectal cancer.

P1a/1b, N=39, Recruiting, Institut de Recherches Internationales Servier | N=129 --> 39 | Trial completion date: Jul 2025 --> Jan 2024 | Trial primary completion date: May 2023 --> Jan 2024

Funding: The study was funded by Institut de Recherches Internationales Servier.Background: Futuximab/modotuximab (Fu/Mo) is a mixture of two monoclonal antibodies that binds to non-overlapping epitopes of the extracellular domain of the anti-epidermal growth factor receptor (EGFR)...Following the results of a phase 2 trial with Fu/Mo in RASwt mCRC, a phase 3 study in combination with trifluridine/tipiracil (TT) was planned with a safety lead-in part to demonstrate the tolerability of the combination. Here we report the results of the first 7 included patients. COLSTAR is a randomized, open-label study comparing Fu/Mo combined with TT to TT monotherapy in RAS/BRAFwt mCRC patients previously treated with chemotherapy (including oxaliplatin, irinotecan, 5-fluorouracil, anti-VEGF and anti-EGFR)... Overall, the combination of Fu/Mo with TT was well tolerated in this cohort of 7 patients and no new safety signals were observed.

Main eligibility criteria include KRAS/NRAS (exons 2, 3 and 4) and BRAF wt (V600E mutation) (double negative; DN) assessed by centralized analysis of ctDNA at screening, and previous treatment with at least 2 regimens including fluoropyrimidine, irinotecan, oxaliplatin, at least one anti-VEGF (bevacizumab, aflibercept, ramucirumab, regorafenib) and at least one anti-EGFR mAb (cetuximab or panitumumab) for ≥4 months. The key secondary endpoint is OS in the triple-negative (KRAS/NRAS, BRAF, and EGFR-ECD wt) population (part 2). A group sequential design with 3 interim analyses (IA) will allow to stop the trial prematurely for futility at each IA as well as for efficacy at last IA.

P3, N=500, Recruiting, Institut de Recherches Internationales Servier | Not yet recruiting --> Recruiting

P3, N=500, Not yet recruiting, Institut de Recherches Internationales Servier

P1a/1b, N=119, Recruiting, Institut de Recherches Internationales Servier

Consistently Sym004 efficacy and potentiation of cisplatin responses correlated with EGFR surface expression in head and neck cancer cells. These findings will have implications in understanding the mode of action of this new class of cancer therapeutics.

P2, N=43, Completed, Annick Desjardins | Active, not recruiting --> Completed | Trial completion date: Aug 2021 --> Apr 2020