Interim results of neoadjuvant immunotherapy with prolgolimab in patients with locally advanced MSI / dMMR colorectal cancer

• DOI: 10.18027/2224-5057-2024-013
• Publication Date: 2024-07-22T14:06:56Z
• Authors: A. A. Zagidullina; O. A. Kuznetsova; M. Yu. Fedyanin; Z. Z. Mamedli; V. A. Aliev; A. V. Polynovskiy; O. A. Malikhova; I. A. Karasev; A. M. Stroganova; A. A. Tryakin
• Keywords: Interim; Cancer Immunotherapy

Introduction: Colorectal cancer is one of the leading malignancies in Russia [1]. The standard approach for selected patients (pts) with locally advanced colon surgery adjuvant chemotherapy. Several studies have shown that colorectal (CRC) presence a disorder mismatch repair (dMMR) / microsatellite instability (MSI) characterized high sensitivity to immune checkpoint inhibitors. MSI dMMR CRC tend be more responsive inhibitors such as pembrolizumab, nivolumab or ipilimumab. However, there was no information about efficacy prolgolimab, PD-1 receptor blocking antibody. Prolgolimab highly effective melanoma treatment, while toxicity comparable pembrolizumab and nivolumab. Methods: We initiated phase II non-randomized open-label clinical trial. Inclusion criteria were: histologically verified, dMMR, stage II–III CRC. According study protocol, prolgolimab (1 mg kg) administered every two weeks, then should done after 6 months immunotherapy (12 cycles). In case surgical treatment refusal, systemic proceeds 1 year. co-primary endpoint complete response (pCR) rate. Secondary endpoints included tumor regression grade by Mandard (TRG), major pathologic (MPR), overall rate (ORR) disease free survival (DFS) (OS). Here presentation safety data — rates pCR MPR, objective Results: A total 26 began from April, 2022 February, 2024. Immune-related adverse effects III–IV, were recorded (3,8 %) patient (autoimmune hepatitis IV); 4 (15,4 had I–II: autoimmune thyroiditis, diarrhea, hypothyroidism. Two refused make because CR possible volume surgery. Nine (34,6 underwent within 3 completion: 7 TRG pCR, 2 MPR treatment. ORR 100 %, 40 %. still ongoing, DFS OS will announced further publications. Median follow-up time 5 months. Conclusion: first interim analysis suggest strong potential neoadjuvant become care allow exploration organ-sparing approaches MMR patients.