Preliminary results from a phase II trial evaluating the safety and efficacy of JS207, a bispecific antibody targeting PD-1 and VEGF, in combination with chemotherapy in patients with metastatic colorectal cancer

Background: JS207 is a bispecific IgG4 antibody targeting programmed death receptor 1 and vascular endothelial growth factor A. This Phase II study (NCT06885385) evaluated the preliminary safety and efficacy of JS207 combined with XELOX (capecitabine + oxaliplatin) as first-line therapy for metastatic colorectal cancer (mCRC). Methods: Patients with mCRC who have not received prior systemic antitumor therapy for metastatic disease, or recurred/progressed at least 12 months after last neoadjuvant/adjuvant therapy were eligible for enrollment. In the initial safety run-in phase, 6 to 9 patients were enrolled to evaluate the safety and tolerability of JS207 10 mg/kg, every 3 weeks with XELOX. Patients received treatment until progression or unacceptable toxicity, with JS207 continued for up to 2 years and oxaliplatin capped at 6-8 cycles, patients then transitioned to capecitabine maintenance therapy. Upon acceptable safety, the study would enter the expansion phase. The primary endpoints were safety, recommended phase III dose, and objective response rate (ORR). Results: As of December 18, 2025, 32 patients were enrolled and received JS207 in combination with XELOX, including 9 in the safety run-in phase and 23 in the dose-expansion phase. All patients were microsatellite stability/mismatch repair proficient CRC. The median age was 61 (range: 36-74) years, with 56% of the patients having primary tumors located in the left‑sided colon and 44% in the right‑sided colon. At baseline, 53% of patients had liver metastases, and 50% had lung metastases. By the cutoff date, the median treatment duration was 3.56 (range: 0.49-7.03) months. The median follow-up was 4.19 (range: 0.82-7.03) months. No dose limiting toxicity was reported. Treatment emergent adverse events (TEAEs) occurred in 96.9% of patients, with grade ≥ 3 TEAEs in 46.9% of patients. The most frequent TEAEs (incidence ≥ 20%) included neutropenia (46.9%), anemia (40.6%), thrombocytopenia (40.6%), leukopenia (37.5%), aspartate aminotransferase increased (28.1%), blood lactate dehydrogenase increased (25.0%), decreased appetite (25.0%), hypoalbuminemia (25.0%), vomiting (25.0%), proteinuria (25.0%), and gamma-glutamyltransferase increased (21.9%). The most common grade ≥3 TEAEs were neutropenia, leukopenia, diarrhea, intestinal obstruction, and malaise, occurring in 2 patients each. Among 31 patients who underwent at least one post-baseline tumor assessment, 21 achieved a partial response and 9 achieved stable disease. The ORR was 67.7% and the disease control rate was 96.8%. At the time of this analysis, the median progression-free survival and median duration of response had not been reached. Conclusions: JS207 in combination with XELOX as first-line treatment for mCRC patients demonstrated an acceptable safety profile and promising efficacy.