Yervoy (ipilimumab)

P=N/A, N=200, Recruiting, Bristol-Myers Squibb

P2, N=35, Recruiting, University of California, Irvine | Trial primary completion date: Jun 2026 --> Oct 2026

P2, N=30, Active, not recruiting, Dana-Farber Cancer Institute | N=45 --> 30

P1, N=18, Recruiting, Washington University School of Medicine | Trial completion date: Jul 2031 --> Jan 2034 | Trial primary completion date: Aug 2026 --> Feb 2029

P1/2, N=33, Completed, Imperial College London | Recruiting --> Completed | Trial completion date: Dec 2023 --> Mar 2026 | Trial primary completion date: Sep 2023 --> Mar 2026

The SWOG S1801 trial demonstrated better event-free survival with perioperative pembrolizumab compared to adjuvant therapy alone. Lastly, the phase III NADINA trial showed that neoadjuvant ipilimumab plus nivolumab followed by response-adapted adjuvant therapy significantly improves outcomes. Biomarkers such as PD-L1, IFN-γ signature, tumor mutational burden and imaging (PET scan) appear promising to predict response, but none have been sufficiently validated for routine clinical practice.

Relative to chemotherapy, early detriment was observed with nivolumab plus ipilimumab across biomarker subgroups but not with nivolumab plus ipilimumab with chemotherapy. Long-term benefit was maintained with both regimens.

ICIs such as nivolumab and pembrolizumab have transformed recurrent/metastatic HNSCC, and their integration into curative settings is under active investigation.We conducted a PRISMA-compliant systematic review of PubMed, Embase, Cochrane Library, and major oncology conference proceedings (2018-2026) to identify clinical trials evaluating ICIs in the perioperative setting of HNSCC...Combination strategies were more effective: the IMCISION trial reported 35% MPR with nivolumab plus ipilimumab vs. 17% with nivolumab alone...Ongoing trials are refining biomarkers, combinations, and sequencing. Perioperative immunotherapy is reshaping curative-intent management of HNSCC, establishing a new multidisciplinary treatment paradigm.

P3, N=626, Active, not recruiting, Ono Pharmaceutical Co., Ltd. | Trial primary completion date: May 2026 --> Oct 2025

P2, N=80, Active, not recruiting, Dan Zandberg | Trial completion date: Oct 2026 --> Oct 2027 | Trial primary completion date: Jul 2026 --> Oct 2027

In 2025, Australia's Pharmaceutical Benefits Advisory Committee adopted a novel broad cancer listing on the Pharmaceutical Benefits Schedule for nivolumab, ipilimumab and pembrolizumab. We suggest that while a broad listing represents a pragmatic response to the growing prevalence of multi-indication medicines, it entails important trade-offs between access, transparency and value alignment. These design considerations are likely to be relevant for other jurisdictions considering similar reimbursement reforms.

In this single-arm, phase I study (NCT04117087), we evaluated mKRAS-VAX, a pooled mutant KRAS (mKRAS) peptide vaccine targeting six KRAS mutations with nivolumab and ipilimumab in 13 patients with pretreated metastatic MMRp/MSS CRC. mKRAS-VAX elicited an increase in tumor-specific mKRAS-reactive T-cells in 8/12 biomarker-evaluable patients (75%) by direct ex vivo IFNγ ELISpot and in 12 patients (100%) following in vitro expansion. Our findings support further development of mKRAS vaccines with ICIs for advanced MMRp/MSS CRC.