Yervoy (ipilimumab)

P2, N=90, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2027 --> Jul 2027 | Trial primary completion date: Mar 2027 --> Jul 2027

P1/2, N=7, Completed, Servier Bio-Innovation LLC | Active, not recruiting --> Completed | N=92 --> 7 | Trial completion date: Mar 2026 --> Nov 2024 | Trial primary completion date: Mar 2026 --> Nov 2024

Patients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Elevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES.

P1/2, N=607, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | N=425 --> 607

P1/2, N=12, Completed, Ultimovacs ASA | Active, not recruiting --> Completed

P=N/A, N=13, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2025 --> Sep 2025

Linrodostat + nivolumab ± ipilimumab demonstrated a manageable safety profile. Kynurenine changes supported IDO1 pathway inhibition but did not correlate with response. A composite biomarker of low TDO2 expression plus high IFN-γ gene expression may predict response to linrodostat + nivolumab.

P2, N=80, Recruiting, Dan Zandberg | Trial completion date: Sep 2027 --> Sep 2026 | Trial primary completion date: May 2027 --> May 2026

P1, N=29, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2026 --> Dec 2024 | Trial primary completion date: Mar 2026 --> Dec 2024

P=N/A, N=40, Completed, ARCAGY/ GINECO GROUP | Active, not recruiting --> Completed

P=N/A, N=825, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

P3, N=925, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

P3, N=1147, Recruiting, Bristol-Myers Squibb | N=831 --> 1147 | Trial primary completion date: Jun 2025 --> Aug 2024

P1/2, N=325, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

P2, N=22, Active, not recruiting, Brown University | Trial completion date: Jul 2024 --> Jan 2025

P2, N=25, Recruiting, University of Utah | Initiation date: Nov 2024 --> Feb 2025

P1, N=30, Recruiting, City of Hope Medical Center | Suspended --> Recruiting

P1, N=6, Terminated, Mayo Clinic | Trial completion date: Jul 2025 --> Apr 2024 | Active, not recruiting --> Terminated; Lack of funding

P2, N=176, Completed, GlaxoSmithKline | Recruiting --> Completed | Trial completion date: Jul 2025 --> May 2024 | Trial primary completion date: Jul 2025 --> May 2024

Results showed antitumour activity and manageable safety with NIVO + RELA. Findings also support NIVO + IPI as an effective combination regimen in IO-naive patients with aRCC.

P=N/A, N=3, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=60 --> 3 | Trial completion date: Nov 2024 --> May 2024 | Recruiting --> Terminated | Trial primary completion date: Nov 2024 --> May 2024; Recruitment challenges: competition with another microbiome trial, patient refusal to join a dietary intervention study, poor tolerance of oral DPD (Grade 2 mucositis), and issues with organizing biological sample collection.

P3, N=906, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

In NSCLC, therapies such as osimertinib have improved efficacy in treating EGFR-mutant BM, with emerging combinations such as amivantamab and lazertinib offering promising alternatives for patients resistant to frontline therapies. In HER2-positive breast cancer, significant advancements with tucatinib and trastuzumab deruxtecan (T-DXd) have transformed the treatment landscape, achieving improved survival and intracranial control in patients with BM. Similarly, in triple-negative breast cancer (TNBC), novel therapies such as sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) offer new hope for managing BM. For melanoma, the combination of immune checkpoint inhibitors such as nivolumab and ipilimumab has proven effective in enhancing survival for patients with BM, both in BRAF-mutant and wild-type cases...Future research should optimise combination therapies, overcome resistance, and refine treatment sequencing. Continued emphasis on personalized, biomarker-driven approaches offers the potential to further improve outcomes, even for complex cases.

Furthermore, patients who received 1L platinum/pemetrexed chemotherapy are often considered for second or further-line (2L+) ipi-nivo on the basis of MAPS2 results. The highest-grade TRAE was 1 to 2 in 58% of these patients and 3 or higher in 42% Treatment discontinuation due to a TRAE occurred in 22% of patients. In this real-world cohort of patients with MPM treated with ipi-nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials, whereas safety outcomes were similar.

P2, N=60, Not yet recruiting, Stanford University

P1/2, N=46, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Oct 2025 --> Apr 2027 | Trial primary completion date: Oct 2024 --> Apr 2026

P1/2, N=104, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Oct 2024

Clinical response evaluated in the first months of therapy is a strong predictor of long-term survival, even in patients with poor prognostic biomarkers.

P2, N=15, Not yet recruiting, M.D. Anderson Cancer Center

Dual Opdivo plus Yervoy immunotherapy, targeting the immune checkpoints PD1 and CTLA-4, is successful in clinical use. Mechanistically, a 6.3-fold increase in PD1/CTLA-4 BsAb accumulation in tumors due to the tumor targeting ability of aPD1, and the PD1/CTLA-4 BsAb significantly reduces the adverse colitis event in healthy mice, compared to aPD1 and aCTLA-4. Thus, these findings provide a novel approach to enhance antitumor therapy using aPD1 and aCTLA-4.

Our results are consistent with those from the Checkmate 067 study, except for the objective response rate and the incidence of toxicities, which proved to be lower in our analysis.

Progression-free survival was longer with nivolumab plus ipilimumab than with chemotherapy among patients who had not previously received systemic treatment for MSI-H or dMMR metastatic colorectal cancer. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 8HW ClinicalTrials.gov number, NCT04008030.).

Compared with chemotherapy alone, Sintilimab or camrelizumab plus chemotherapy seemed to achieve the best progression-free survival (hazard ratio = 0.56, 95% CI 0.46-0.68)...Nivolumab plus ipilimumab resulted in a relatively lower incidence of adverse events of grade ≥3 than other regimens. The combination of immune checkpoint inhibitors (ICIs) with chemotherapy provided a high probability of more effective treatment in comparison with chemotherapy alone for patients with advanced ESCC. Toripalimab and sintilimab plus chemotherapy were ranked as providing the highest OS and PFS benefit in the first-line setting, respectively.

In this retrospective study, we searched for a gene signature potentially predictive of the response to the addition of cetirizine to checkpoint inhibition (nivolumab or pembrolizumab with or without previous ipilimumab). ICOSLG expression was associated with CD64, a specific marker of M1 macrophages, at baseline in the patient samples who received cetirizine concomitantly with checkpoint inhibitors, but this association was not present in subjects who had not received cetirizine. In conclusion, our results show that the clinical advantage of concomitant treatment with cetirizine during checkpoint inhibition in patients with malignant melanoma is associated with high ICOSLG expression, which could predict the response to immune checkpoint inhibitor blockade.

P2, N=14, Active, not recruiting, Georgetown University | Suspended --> Active, not recruiting | N=27 --> 14 | Trial completion date: May 2024 --> Dec 2024

P1/2, N=29, Completed, Anaveon AG | Recruiting --> Completed | N=130 --> 29 | Trial completion date: Dec 2024 --> Aug 2024

P3, N=26, Completed, Bristol-Myers Squibb | Terminated --> Completed

This study presents the first results of ipilimumab-nivolumab in invasive mucinous or non-mucinous lepidic adenocarcinoma (invasive mucinous adenocarcinoma (IMA) or invasive non-mucinous lepidic adenocarcinomas (INLA), respectively) of the lung. Expanded prospective studies are warranted. ClinicalTrials.gov registry: NCT02834013.

P2, N=25, Recruiting, Brown University | Trial completion date: Jan 2025 --> Apr 2025 | Trial primary completion date: Oct 2024 --> Feb 2025

P3, N=40, Recruiting, Vastra Gotaland Region | Not yet recruiting --> Recruiting

P2, N=46, Active, not recruiting, Brown University | Trial completion date: Dec 2025 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Mar 2025

Fifteen patients were treated, with four patients on dexamethasone at treatment initiation and five tumors having MGMT promoter methylated. We show nivolumab plus ipilimumab can be safely administered prior to standard radiotherapy for newly diagnosed gliomas and is operationally feasible. Clinicaltrials.gov NCT03425292 registered February 7, 2018.