JMT101 in combination with irinotecan and SG001 versus regorafenib in patients with metastatic colorectal adenocarcinoma (mCRC): Results of a randomized, controlled, open-label, phase II study.

Abstract

LBA3516 Background: Both Becotatug (JMT101, humanized IgG1 anti-EGFR monoclonal antibody [mAb]) ± chemotherapy, and Enlonstobart (SG001, humanized IgG4 anti-PD-1 mAb), demonstrated promising antitumor activity with favorable safety in advanced solid tumors. This study evaluates the safety and preliminary efficacy of JMT101 + SG001 + irinotecan in patients (pts) with metastatic colorectal adenocarcinoma (mCRC). Methods: This multicenter, randomized, open-label phase II study enrolled pts with histologically or cytologically confirmed RAS/BRAF wild-type mCRC without MSI-H/dMMR, who had progressed after ≥ 2 prior systemic therapies. Upon dose confirmation in safety run-in part (SRI, 3-6 pts, JMT101 6 mg/kg + irinotecan 180 mg/m 2 + SG001 240 mg Q2W), eligible pts, stratified by PD-L1 expression (+/-), were randomized 1:1:1 to receive either JMT101 + irinotecan + SG001 (Arm A), JMT101 + irinotecan (Arm B), or regorafenib 160mg QD, days 1-21 of 28-day cycles (Arm C). The primary endpoint is the ORR per RECIST v1.1 by investigator. Results: After the SRI in 3 pts, 106 additional pts (median age 58 yrs [25-74], 62.3% male) were randomized (36/35/35 in Arm A/B/C). As of Jan 24, 2025, all SRI pts and 69/106 (65.1%) randomized pts (18/21/30 in Arm A/B/C) completed treatment. The median follow-up was 7.4 months, with 34, 35, 34 efficacy-evaluable pts in Arm A, B, and C, respectively. Detailed efficacy data are shown in the table. Arm A and B had comparable ORR, DCR, and PFS, all statistically superior to Arm C. The median OS was not reached. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 38.9% (14/36), 54.3% (19/35), and 48.6% (17/35) pts in Arm A, B, and C, respectively. No TRAEs led to discontinuation in Arm A/B, compared to 2/35 (5.7%) in Arm C. No TRAEs leading to death occurred. Conclusions: Our results demonstrated a promising response rate and a tolerable safety profile of JMT101 + irinotecan +/- SG001 in pts with mCRC. Preliminary data support continued investigation, with updated results to follow. Clinical trial information: NCT06089330 . CR PR SD PD NE ORR RD* DCR RD * 6 mo-DoR mPFSmo (95%CI) P value # SRI 0 1 (33.3) 0 2 (66.7) 0 33.3 (0.84, 90.6) / 33.3 (0.84, 90.6) / / 2.0 (0.92, NR) / Arm A 0 15 (44.1) 13 (38.2) 4 (11.8) 2 (5.90) 44.1 (27.2, 62.1) 41.2 (23.7, 58.6) 82.4 (65.5, 93.2) 20.6 (0.06, 41.1) 48.0 (12.7, 77.0) 5.7 (3.75, NR) 0.003 Arm B 0 12 (34.3) 18 (51.4) 5 (14.3) 0 34.3 (19.1, 52.2) 31.1 (14.6, 47.5) 85.7 (69.7, 95.2) 23.9 (3.85, 43.9) 71.4 (25.8, 92.0) 7.4 (3.91, NR) <0.001 Arm C 0 1 (2.90) 20 (58.8) 13 (38.2) 0 2.9 (0.07, 15.3) Ref. 61.8 (43.6, 77.8) Ref. / 2.9 (2.14, 3.71) 1.000 Data are n (%) or % (95% CI), unless noted. * Rate difference, analyzed by Cochran-Mantel-Haenszel test. # Estimated via stratified log - rank test, stratifying by PD-L1 expression (+/-).