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

Background

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.

Methods

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).

Results

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.

Conclusions

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.

Clinical trial identification

NCT04856787.

Editorial acknowledgement

We would like to acknowledge Lin Dong (a Medical Writer from Jiangsu Hengrui Pharmaceuticals) for providing writing assistance in the preparation of this abstract.

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd, China.

Disclosure

C. Huang, Y. Jiang: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd. All other authors have declared no conflicts of interest.