611P SHR-1701 in Combination with BP102 and XELOX As First-Line (1L) Treatment for Patients (pts) with Unresectable Metastatic Colorectal Cancer (mcrc): Data from a Phase II/III Study

The standard 1L therapies for mCRC involve a fluoropyrimidine with oxaliplatin and/or irinotecan, and a biologic agent. SHR-1701, a novel bifunctional fusion protein targeting PD-L1 and TGFβ, may enhance antitumor activity in combination with 1L standard therapies in mCRC pts. This phase 2/3 trial was designed to evaluate the safety and efficacy of SHR-1701 in combination with BP102 (a biosimilar of bevacizumab) and XELOX as 1L treatment in this pt population. In the phase 2 part, eligible pts with previously untreated, unresectable mCRC were given SHR-1701 (30 mg/kg, iv, d1, q3w) + BP102 (7.5 mg/kg, iv, d1, q3w) + XELOX (capecitabine 1000 mg/m2, po bid, d1-14, and oxaliplatin 130 mg/m2, iv, d1) of 21-day cycles. Primary endpoints were safety and objective response rate (ORR) per investigator according to RECIST v1.1. Secondary endpoints were duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). From June 22 2021 to February 28 2023, 62 pts were enrolled. Median age was 56 years (range, 23-73). The main characteristics of the pts were as follows: 22 (35.5%) right-sided mCRC, 43 (69.4%) had liver metastases, 62 (100.0%) had MSS/pMMR, 36 (58.1%) had RAS mutation, and 4 (6.5%) had BRAF mutations. As of February 28, 2023, the median follow up time was 12.5 months (range, 1.4-18.8). Grade ≥3 TRAEs were reported in 37 (59.7%) pts, with the most common being anemia (8.1%), decreased neutrophil count (6.5%), and anaphylactic reaction (4.8%). TRAEs led to discontinuation of any study agent in 12 (19.4%) pts; of these, 6 (9.7%) discontinued SHR-1701 due to TRAEs (1 in grade 1, 3 in grade 3 and 2 in grade 4). This combination regimen resulted in an ORR of 59.7% and a DCR of 83.9%. Median DoR was 10.7 months (95% CI, 8.4-13.0). Median PFS was 10.3 months (95% CI, 8.3-13.7), and median OS was immature. SHR-1701 in combination with BP102 and XELOX as 1L treatment provided a manageable safety profile and potent antitumor activity in pts with unresectable mCRC.