Ipilimumab/nivolumab plus panitumumab in patients with microsatellite-stable mCRC

Presented by

Dr Michael Lee, University of Texas MD Anderson Cancer Center, USA

Conference

ASCO GI 2021

Trial

Phase 2

Based on preclinical studies, it was hypothesised that the combination of anti-epidermal growth factor receptor (anti-EGFR) treatment with dual checkpoint inhibition could be beneficial for patients with KRAS/NRAS/BRAF wildtype microsatellite-stable metastatic colorectal cancer (mCRC). The phase 2 clinical trial met its primary endpoint with at least 35% response rate at 12 weeks.

Anti-EGFR treatment with panitumumab is a standard therapy in patients with KRAS/NRAS/BRAF wildtype mCRC. However, anti-EGFR antibody therapy resistance and increased expression of CTLA-4 and PD-L1 commonly develop. The aim of the study presented by Dr Michael Lee (University of Texas MD Anderson Cancer Center, USA) was to assess the efficacy of a combined treatment with anti-PD-1 (nivolumab) and anti-CTLA-4 antibodies (ipilimumab) with anti-EGFR therapy (panitumumab) in a multicentre, single-arm, phase 2 clinical trial (NCT03442569) in these patients [1].

Eligible patients received 1-2 prior lines of therapy and no prior anti-EGFR or immune checkpoint inhibitor therapy. Subjects received ipilimumab 1 mg/kg IV every 6 weeks, nivolumab 240 mg IV every 2 weeks, and panitumumab 6 mg/kg IV every 2 weeks until progression, toxicity, or patient withdrawal. Response rate at 12 weeks (per RECIST 1.1) served as the primary endpoint, key secondary endpoints included progression-free survival (PFS) and duration of response.

First, 6 patients were enrolled in a pre-specified safety run-in cohort. No dose-limiting toxicities were observed within the first 12 weeks. The first stage of the clinical trial (n=32) had sufficient response rate to merit full enrolment and a total of 56 subjects were included in this study. Among the 49 evaluable subjects, 17 patients (35%) showed a 12-week response rate and 20 patients (41%) showed at least an unconfirmed response at any time. Median PFS was 5.7 months (95% CI 5.5-7.9 months), median overall survival was 27 months (95% CI 14.5-not evaluable). Given that the pre-specified number of 12-week responders was 17 patients, the study met its primary endpoint.

There were 2 grade 5 adverse events: myocarditis, which was possibly related to treatment and colonic perforation, which was unlikely related. Grade 3-4 adverse events included increase of lipase, amylase, ALT and AST, and diarrhoea. Toxicities were thus consistent with the expected adverse event profiles of the drugs used.

Dr Lee concluded that the combination of panitumumab, ipilimumab, and nivolumab met its primary endpoint with a 35% 12-week response rate and demonstrated promising activity in second- or third-line KRAS/NRAS/BRAF wildtype microsatellite-stable mCRC.

Lee MS, et al. Phase II study of ipilimumab, nivolumab, and panitumumab in patients with KRAS/NRAS/BRAF wild-type (WT) microsatellite stable (MSS) metastatic colorectal cancer (mCRC). ASCO Gastrointestinal Cancers Symposium 2021, 15-17 January. Abstract 7.

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