Single-arm, phase 2 study of regorafenib plus nivolumab in patients with mismatch repair-proficient (pMMR)/microsatellite stable (MSS) colorectal cancer (CRC).

• DOI: 10.1200/jco.2021.39.15_suppl.3560
• Publication Date: 2021-06-02T14:02:23Z
• Authors: Marwan Fakih; Kanwal Pratap Sin...; David Z. Chang; Johanna C. Bendell; Timothy Larson; Allen Lee Cohn; Timothy K. Huyck; David Cosgrove; Joseph A. Fiorillo; Lawrence E. Garbo; Shruthi Ravimohan; Von Potter; David D'Adamo; Neelesh Sharma; Ying A. Wang; Sabine Coppieters; Matthias Herpers; Carolina Soares V...; Andrew Scott Paulson
• Keywords: Regorafenib; Clinical endpoint

3560 Background: The role of immunotherapy in the treatment pMMR/MSS metastatic CRC is not established. A Japanese phase 1b trial this setting showed combination regorafenib (multikinase inhibitor with immunomodulatory activity) plus nivolumab (anti PD-1) had encouraging activity and manageable safety (Fukuoka, 2020). This study further assessed efficacy combination. Methods: Patients (pts) from US aged ≥18 years who progressed on/were intolerant to standard chemotherapy were enrolled. Regorafenib was given orally, once daily 28-day (D) cycles (21D on/7D off) IV 480 mg on D1. starting dose 80 mg; if well tolerated, it could be escalated 120 Cycle 2. Primary endpoint overall response rate (ORR; RECIST 1.1); secondary aims included disease control (DCR), survival (OS), progression-free (PFS), (NCI-CTCAE v5.0 grade). Biomarker analysis exploratory. Results: 70 pts (59% male) started treatment. At baseline, median age 57 (range 34–85), ECOG PS 0/1 51%/49%, 67% liver metastases (mets), primary tumor site right-sided colon 36% rectum 17%. Median number 3.0 1–13); 41% mg. Five (7.1%) a partial (PR) lasting ≥16 weeks (wks) 22 (31.4%) stable (SD); without mets higher ORR (21.7%). In samples (n = 40), baseline expression (IHC) cytotoxic T cells (CD3+/CD8+/GranzymeB+), Tregs (FoxP3+), macrophages (CD68+) trended clinical benefit (PR/SD wks/PFS); lower expression. Lower plasma levels biomarkers vascular biology (e.g. VEGF-D, Ang-2, VWF) longer PFS. Grade (Gr) 3 treatment-emergent adverse events (TEAEs) occurred 53% Gr 4 10%. Three 5 TEAE: n 1 related (sepsis); only by investigator unrelated (respiratory failure). Most common 3/4 TEAEs: maculopapular rash (14%), fatigue (7%), pneumonia (6%), increased bilirubin (6%). Conclusions: Combination (up mg/day) (480 every 28D) has safety. Efficacy North American population did emulate results population. Absence specific indicate better may warrant analysis. Clinical information: NCT04126733. [Table: see text]