Durvalumab (MEDI 4736) with extended neoadjuvant regimens in rectal cancer: A randomized phase II trial (PRIME-RT)

Abstract

Background: Advances in multi-modality treatment of locally advanced rectal cancer (LARC) have resulted in low local recurrence rates, but many patients still die from distant disease. There is increasing recognition that with neoadjuvant treatment some patients achieve a complete response and may avoid surgical resection. The PRIME-RT trial tests the inclusion of neoadjuvant immunotherapy with the aim of enhancing complete response rates, improving stoma-free survival and reducing distant relapse. Methods: PRIME-RT is a multi-centre, open label, phase II, randomised trial for patients with newly diagnosed LARC. Eligible patients are randomised to Arm A: short course radiotherapy (25 Gray in 5 fractions) with concomitant durvalumab, followed by durvalumab and FOLFOX chemotherapy, or Arm B: long course chemoradiotherapy (50 Gray to primary tumour, 45 Gray to elective nodes, in 25 fractions with capecitabine) with concomitant durvalumab followed by FOLFOX and durvalumab. The primary endpoint is complete response rate in each arm. Bio-specimens including serial tumour biopsies and peripheral blood samples are collected prior to, during, and following treatment to explore the molecular and immunological factors underpinning treatment response. The main trial will recruit up to 42 patients and commence after a safety run-in (n≥6) which is recruiting patients with metastatic disease. After opening in January 2021, three patients have been treated within the safety run-in; 2 in Arm A and 1 in Arm B. Early recruitment to PRIME-RT has shown that adding immunotherapy in the neoadjuvant setting for LARC is feasible. The expectation is that the trial will provide efficacy and safety information which allows the optimal treatment approach to be tested within a larger phase clinical trial.