Phase II trial of nivolumab and metformin in patients with treatment refractory microsatellite stable metastatic colorectal cancer.

• DOI: 10.1200/jco.2021.39.3_suppl.95
• Publication Date: 2021-01-22T19:59:19Z
• Authors: Mehmet Akce; Manali Rupji; Jeffrey M. Switch...; Walid Labib Shaib; Christina Wu; Olatunji B. Alese; Maria Diab; Gregory B. Lesinski; Bassel F. El-Rayes
• Keywords: Clinical endpoint; Refractory (planetary science)

95 Background: Preclinical data suggests metformin can improve immune exhaustion of tumor infiltrating lymphocytes and potentiate the effects PD-1 blockade. By normalizing hypoxic TME, was shown to cytotoxic T cell function efficacy anti-PD-1 antibody in highly aggressive B16 melanoma MC38 colon adenocarcinoma models. Based on this preclinical rationale we conducted a phase II study with nivolumab combination treatment refractory MSS metastatic colorectal cancer (mCRC). Methods: Nivolumab 480 mg IV every 4 weeks Metformin 1000 po twice daily administered 28-day cycles following 14-day only lead-in phase.Eligible patients included stage mCRC (patients must have received oxaliplatin, irinotecan, fluoropyrimidine), age ≥18 years, ECOG PS 0-1, adequate organ function, no prior anti agent. The primary endpoint overall response rate (ORR). Secondary endpoints survival (OS) progression free (PFS). Simon’s two-stage Minimax design employed (H 0 : ORR =4%; H 1 ORR=15%; alpha = 0.1; power =80%). If ≥1 objective observed first evaluable 18 patients, 10 additional would be cohort. ≥3 responders 28 required considered positive study. Pre-treatment on-treatment research biopsies correlative peripheral blood specimens were collected. Results: A total 24 enrolled, 6 replaced per protocol, had disease. Of 11/18 (61%) female, median 58 [IQR 50-67]. 2 prolonged stable disease (4 cycles). No based RECIST 1.1. Median OS PFS 5.1 months [95% CI (2-11.7)] 2.3 (1.7-2.4)], respectively. Most common grade 3 toxicities anemia (n=2) diarrhea (n=2). Conclusions: In mCRCnivolumab well tolerated. Two achieved disease, but seen; therefore, did not proceed second enrollment. Immunologic analysis is ongoing. Clinical trial information: NCT03800602.