LBA23 - Avelumab versus standard second-line treatment chemotherapy in metastatic colorectal cancer (mCRC) patients with microsatellite instability (MSI): The SAMCO-PRODIGE 54 randomised phase II trial

Background

Immune checkpoint inhibitors have failed in treating mCRC patients (pts) except those with MSI/dMMR tumours. However, in pts with MSI/dMMR mCRC, only one randomized trial in the first-line setting, showed the superiority of an anti-programmed death 1 (anti–PD-1) antibody over standard treatment. The SAMCO-PRODIGE 54 trial aimed to evaluate efficacy and safety of an anti-programmed death ligand-1 (anti–PD-L1) antibody compared with a standard treatment in the second-line setting in pts with MSI/dMMR mCRC.

Methods

In this national, multi-center, open-label phase 2 trial, pts with MSI/dMMR mCRC who progressed on oxaliplatin or irinotecan-based first-line therapy ± targeted agents, were randomized to receive standard second-line therapy or avelumab (10 mg/kg q2w). Primary endpoint was progression-free survival (PFS) according to RECIST 1.1 criteria, evaluated by investigators, in pts with confirmed MSI/dMMR status and that received at least one dose of planned treatment (modified intention-to-treat [mITT] population). Pts were stratified on WHO performance status (0-1 vs 2), BRAF V600E status and age (< 70 years vs ≥ 70 years).

Results

From April 2018 to April 2021, in 49 French sites, 122 pts were enrolled in the mITT population for efficacy analyses (61 in arm A: control; 61 in arm B: avelumab). There were no differences in pts and tumours characteristic between the two arms.No new safety concern in either arms have been detected. After a median follow-up of 33.3 months (range, 28.3 to 34.8), avelumab was superior to chemotherapy +/- targeted agents with respect to PFS (p=0.025). 12- and 18-month PFS rates were 19% and 9% in arm A, and 31% and 27%, in arm B. Objective response rates were similar in both arms (28% vs 30%, p=0.45). Among pts with a disease control, 75% in the avelumab group, compared with 20% in the control group, had ongoing disease control at 18 months. Treatment-related adverse events ≥ grade 3 occurred in 31.7% of the pts in the avelumab group, compared with 53.1% in the control group.

Conclusions

The SAMCO-PRODIGE 54 randomized phase II study demonstrated, in second-line for dMMR/MSI mCRC pts, the safety and efficacy of avelumab.

Clinical trial identification

NCT 03186326.

Editorial acknowledgement

Legal entity responsible for the study

FFCD.

Funding

Merck Serono.

Disclosure

J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Roche, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis, Pierre Fabre, Roche, Servier; Non-Financial Interests, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships /partnership for FFCD in the prodige intergroup: Federation Francophone de Cancerologie Digestive (FFCD). T. André: Financial Interests, Personal, Advisory Board, Advosiry Board on February 12, 2021: Astellas pharma; Financial Interests, Personal, Advisory Board, Advisory Board on February 2021: Kaleido Biosciences; Financial Interests, Personal, Invited Speaker, and advisory board: Amgen; Financial Interests, Personal, Invited Speaker, Invited speaker in a symposuim december 2020: AstraZeneca; Financial Interests, Personal, Advisory Board, and consultant fees and consultant contract: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory board in Janaury 2020: Clovis; Financial Interests, Personal, Advisory Board, Advisory board in january 2020: Gritstone Oncology; Financial Interests, Personal, Advisory Board: Haliodx; Financial Interests, Personal, Advisory Board, and consultant fees/consultant contract and invited speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker, and other: Pierre Fabre; Financial Interests, Personal, Invited Speaker, in an symposium in 2020: Roche; Financial Interests, Personal, Invited Speaker, in a meeting in 2019: Ventana; Financial Interests, Personal, Invited Speaker, In a educational meeting in 2019: Sanofi; Financial Interests, Personal, Advisory Board, in a symposium in 2020: Servier; Financial Interests, Personal, Expert Testimony, Consultant with personnal fees and invited speaker: Servier; Financial Interests, Personal, Advisory Board, in 2019: GSK; Financial Interests, Personal, Invited Speaker, in 2020 and 2021: GSK; Financial Interests, Personal, Expert Testimony, consultant contract: Seagen; Financial Interests, Personal, Invited Speaker, Virtual symposium Lecture: 1 MSI-H CRC: Implementation of Immunotherapy in clinical practice (30 minutes) – (this will be pre-recorded)Q&A – Live Q&A – (10 minutes) (on July 2, 2021): MSD Oncology; Financial Interests, Personal, Invited Speaker, June 2022: Sanofi; Financial Interests, Personal, Expert Testimony, Contract: Merck & Co., Inc, Gritstone Oncologie; Financial Interests, Personal, Advisory Board, Contrat: BMS; Financial Interests, Institutional, Other, Investigator and scientific comitee president: Gercor Academic group; Financial Interests, Institutional, Invited Speaker, PI Garnet study: GSK; Financial Interests, Institutional, Invited Speaker, Keynote 164 and 171 and 811: MSD; Financial Interests, Institutional, Invited Speaker, BMS CA209-8HW, BMS CA209-142, BMS CA209-577: BMS; Financial Interests, Institutional, Invited Speaker, SPOTLIGHT study: Astellas; Financial Interests, Personal, Invited Speaker, and internationnal PI: Servier; Non-Financial Interests, Invited Speaker, Vice President: Gercor group; Non-Financial Interests, Invited Speaker, Member of scientific committee: ARCADFoundation. All other authors have declared no conflicts of interest.