Nivolumab combination therapies in patients with advanced gastric and gastroesophageal junction cancer: the phase II FRACTION gastric cancer study
Background - Nivolumab-based therapies are efficacious with acceptable safety in patients with gastric cancer (GC) and gastroesophageal junction cancer (GEJC). Novel nivolumab-based combination immunotherapies may offer enhanced efficacy in these indications. FRACTION-GC was a signal-seeking, random...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
10 January 2025
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| In: |
ESMO open
Year: 2025, Volume: 10, Issue: 2, Pages: 1-10 |
| ISSN: | 2059-7029 |
| DOI: | 10.1016/j.esmoop.2024.104107 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.esmoop.2024.104107 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2059702924018787 
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| Author Notes: | G. Ku, G.M. Haag, H. Park, V.K. Lam, T.J. George, S.S. Kim, M. Gutierrez, V. Shankaran, S. Stein, C.S. Denlinger, E. Elimova, A. Nagrial, A.R. He, M.B. Sawyer, H.H. Yoon, R. Geva, J. Starr, G. Curigliano, T. Golan, R. von Moos, R. Fritsch, D. Lim, Q. Wang, A. Patel, T. Aoyama, M. Lei, D. Greenawalt, and M. Di Bartolomeo |
| Summary: | Background - Nivolumab-based therapies are efficacious with acceptable safety in patients with gastric cancer (GC) and gastroesophageal junction cancer (GEJC). Novel nivolumab-based combination immunotherapies may offer enhanced efficacy in these indications. FRACTION-GC was a signal-seeking, randomized, open-label, phase II adaptive-design trial assessing efficacy and safety of nivolumab in combination with ipilimumab [cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody], relatlimab (lymphocyte-activation gene 3 antibody), or IDO1i (BMS986205, an indoleamine-2,3-dioxygenase-1 inhibitor) in patients with unresectable, advanced/metastatic GC/GEJC. - Patients and methods - Previously treated patients with GC/GEJC were randomized to receive nivolumab + ipilimumab, nivolumab + relatlimab, or nivolumab + IDO1i across two tracks: anti-programmed death-(ligand) 1/anti-CTLA-4-naïve (track 1) and -experienced (track 2). Primary endpoints were objective response rate (ORR) by investigator per RECIST v1.1, duration of response, and progression-free survival (PFS) rate at 24 weeks. Secondary endpoint was safety. - Results - Eighty-one patients in track 1 and 81 in track 2 received one combination therapy. With a median follow-up of 50.2 months, ORR [95% confidence interval (CI)] by investigator for nivolumab + ipilimumab, nivolumab + relatlimab, and nivolumab + IDO1i in track 1 was 4% (0.1% to 21.9%), 5% (0.1% to 24.9%), and 13% (4.4% to 28.1%), and for track 2 was 9% (1.1% to 28.0%), 6% (0.7% to 18.7%), and 0% (0% to 15.4%), respectively. PFS rate at 24 weeks (95% CI) was 24% (11% to 39%) for nivolumab + IDO1i track 1, 17% (16% to 32%) for nivolumab + relatlimab track 2, and not estimable for other treatment arms. Grade 3/4 treatment-related adverse events were reported in 22%, 5%, and 18% of patients receiving nivolumab + ipilimumab, nivolumab + relatlimab, and nivolumab + IDO1i in track 1 and in 35%, 11%, and 18% of patients in track 2, respectively. No treatment-related deaths were reported. - Conclusions - While ORR did not meet prespecified expansion criteria in any treatment arm, the safety profile of the combinations was manageable. FRACTION-GC represents a novel adaptive protocol for testing multiple combination immunotherapies. |
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| Item Description: | Gesehen am 15.07.2025 |
| Physical Description: | Online Resource |
| ISSN: | 2059-7029 |
| DOI: | 10.1016/j.esmoop.2024.104107 |