Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial

Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial.

Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial

Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): a phase 1–2, open-label, multicohort trial

The combination of nivolumab and ipilimumab is approved in several jurisdictions (United States, European Union, Canada) for the first-line treatment of patients with advanced melanoma. CheckMate 218 is a North American expanded-access program (eap) of nivolumab plus ipilimumab in patients with advanced melanoma. Here, we report safety and survival outcomes for the Canadian cohort in the eap. Eligible patients were those 18 years of age or older with unresectable stage iii or iv melanoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior anti-PD-1 or anti-ctla-4 therapy. Patients were treated with nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks for 4 cycles (induction phase); they then continued with nivolumab 3 mg/kg every 2 weeks (maintenance phase) until progression, unacceptable toxicity, or a maximum of 48 weeks, whichever occurred first. Safety and overall survival (os) data were collected. Of 194 patients enrolled, 174 were treated, and 51% continued on nivolumab maintenance. Median follow-up was 12.9 months. All-grade and grades 3-4 treatment-related adverse events were reported in 98% and 60% of patients respectively and led to treatment discontinuation in 40% and 28% of patients. Two treatment-related deaths were reported. The 12- and 18-month os rates were 80% [95% confidence interval (ci): 73% to 86%] and 76% (95% ci: 67% to 82%) respectively. In this Canadian population, nivolumab plus ipilimumab demonstrated a safety profile and survival outcomes consistent with phase ii and iii clinical trial data.

Cells to Surgery Quiz: May 2019

Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study.

ObjectivesOn the basis of the positive results of CheckMate-743, first-line (1L) treatment of malignant pleural mesothelioma (MPM) with the combination of ipilimumab and nivolumab (ipi-nivo) has become a standard-of-care. 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. Here we report on real-world survival and safety outcomes of ipi-nivo for patients with MPM in Switzerland. MethodsTwelve cancer centers contributed data to this retrospective cohort. Baseline characteristics including age, sex, histology, programmed death-ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS), and previous/subsequent therapies were collected. The efficacy and safety outcomes were assessed by local investigators. ResultsOf the 109 patients with MPM treated with ipi-nivo between November 2017 and March 2023 (median follow-up of 16.6 months) 75% had epithelioid, 9% biphasic, and 16% sarcomatoid histology. The median age was 72 years; 91% were males, and 83% had an ECOG PS of 0 to 1. Ipilimumab in combination with nivolumab was given as 1L in 43% and as 2L+ treatment in 57% of patients. The objective response rate was 21% in 1L and 15% in 2L+. Median progression-free survival was 6.5 and 2.8 months, respectively. Median overall survival (OS) from the start of ipi-nivo was 12.6 months for 1L and 6.9 months for 2L+. No differences in OS were observed depending on age and programmed death-ligand 1 expression. Nevertheless, the median OS was significantly worse in patients with an ECOG PS of 2 or higher than those with an ECOG PS of 0 to 1 (2.4 versus 11.9 months, p < 0.001). Treatment-related adverse events (TRAEs) of any grade related to ipi-nivo treatment occurred in 65 patients (62%). 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. ConclusionIn 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.

Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial

Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial

MS28.02 Combination IO+IO

Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial

Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial

Cytoreduction and the Optimization Of Immune Checkpoint Inhibition with Radiation Therapy

BackgroundIpilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively,have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintains a long-lasting effect. Even Ipilimumab, in combination with nivolumab, has demonstrated a significant clinical benefit in multiple tumor types. However, no trial has been designed with the primary endpoint to compare the efficacy of nivolumab plus ipilimumab combined, compared to nivolumab alone. Hence, the added value of ipilimumab in the combination has not clearly been established yet. The aim of this study was to demonstrate the superiority of the combination strategy compared to the single agent therapy.Materials and methodsWe performed a meta-analysis of Phase I-II-III Clinical Trials, published from 2010 up to 2020, in which the combination of ipilimumab plus nivolumab was compared to nivolumab alone. We extracted ORR, OS and PFS HR on the basis of treatment from the subgroup analysis of each trial.ResultsA total of 7 trials were included in the present meta-analysis. Overall, 1313 patients were treated with the nivolumab plus ipilimumab combination compared to 1110 patients treated with nivolumabalone. All trials reported the Objective response rate(ORR), no heterogeneity was found among studies and the pooled Odds Ratio was highly in favor of the nivolumab plus ipilimumab combination with respect to nivolumab alone (1.683; 95% CI: 1.407–2.012; P < 0.0001). Three studies were considered for Progression free survival (PFS) analysis, and the pooled Hazard Ratio favored the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.807; 95% CI: 0.719–0.907; P < 0.0001). The Overall survival(OS) endpoint was considered only in 2 trials, and the pooled HR favored, also in this case, the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.87; 95% CI: 0.763–0.997; P = 0.045).ConclusionsThe combination of ipilimumab plus nivolumab seems to be superior to nivolumab alone in cancer patients, regardless of histology.

Nivolumab Combined with Brentuximab Vedotin for Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Preliminary Results from the Phase 2 CheckMate 436 Trial