Abstract 6002: Tyrosine kinase inhibitor (TKI) plus PD-1 blockade in TKI-responsive MSS/pMMR metastatic colorectal adenocarcinoma (mCRC): Results of a multicenter, phase II trial (TRAP)

Abstract Background: There is an unmet need in immunotherapy for patients (pts) with MSS/pMMR mCRC. PD-1 blockade combined with antiangiogenic therapy has synergistic effects and has shown clinical benefits in these pts in several studies. TRAP (NCT04483219) aims to explore the efficacy and safety of antiangiogenic TKIs combined with PD-1 blockade in TKI-responsive MSS/pMMR mCRC pts refractory to standard treatment. Methods: Eligible pts were given 1 cycle of TKIs (fruquintinib 5mg or regorafenib 120mg, d1-21, q4w) and grouped by tumor response according to RECIST v1.1: arm A: reduction of target lesion to CR, PR or shrunken SD, or cavitation in metastatic lung lesions, or decrease in the density of liver metastatic target lesions ≥15%; arm B: enlarged SD; arm C: PD. Then arm B pts were given another cycle of TKIs and grouped again. Pts in arm A then received TKIs plus anti-PD-1 antibody (toripalimab 240mg, or sintilimab 200mg, i.v.gtt, q3w, until PD or up to 2 years), pts in arm B continued with TKIs until PD. The Simon 2-stage design tested the null 9-months (m) PFS rate of 27.1% vs. 55% (power = 0.90; α = 0.05). A total of >10 pts reaching ≥ 9-m PFS in 25 pts receiving TKI plus anti-PD-1 antibody is required to reject null hypothesis. Results: As of Sep 16, 2024 (data cutoff), 58 eligible pts were enrolled. Median age, 60 (34-75); male, 56.9%; ECOG PS 1, 96.6%; KRAS mutation, 48.3%; median prior regimens, 2 (1-4); prior anti-VEGF, 73.7%; prior anti-EGFR, 28.1%. 25 pts entered arm A and 29 entered arm C. Baseline characteristics of arm A were generally consistent with the overall population. In arm A, ORR was 20.0% (95%CI, 6.8%-40.7%). Median PFS was 11.5m (95% CI, 7.31-18.9), 6-m, 9-m and 12-m PFS rates were 87.1% (95% CI, 74.4%-100%), 58.1% (95% CI, 40.4%-83.4%) and 42.6% (95% CI, 25.7%-70.6%), respectively. At median follow-up of 31.1m (95% CI, 29.0-NA), median OS was 24.7m (95% CI, 17.0-NA), 12-m, 24-m and 36-m OS rates were 82.4% (95% CI, 68.1%-99.7%), 53.3% (95% CI, 35.6%-79.6%) and 35.5% (95% CI, 19.2%-65.5%), respectively. Median PFS and median OS were numerically longer in fruquintinib versus regorafenib treated pts (13.21m [95%Cl: 7.31-NA] vs 8.95m [95%CI: 6.82-NA], p=0.38; 29.0m [95%Cl: 17.0-NA] vs 19.5m [95%CI: 16.9-NA], p=54) and in KRAS wild-type and KRAS mutant pts (13.21m [95%CI: 8.95-NA] vs 7.31m [95%Cl: 4.85-NA], p=0.21; 26.6m [95%CI: 17.9-NA] vs 15.0m [95%Cl: 14.2-NA], p=0.24). The most common treatment-related adverse events (TRAEs) (total; Grade ≥3) were hand-foot skin reaction (43.8%; 18.8%), hypothyroidism (37.5%; 6.3%), hypertension (31.2%; 25.0%) and proteinuria (31.2%; 6.3%). No treatment related death was observed. Conclusions: TKIs combined with PD-1 blockade has shown encouraging efficacy with acceptable toxicities in MSS/pMMR mCRC pts responsive to TKI treatment. The regimen could be a preferred approach in pretreated MSS/pMMR mCRC. Citation Format: Jingdong Zhang, Qian Dong, Yuanhe Wang, Yanwen Diao, Xiujie Cui, Li Man, Jian Zhang, Yuyang Zhang, Tao Wu, Tiejun Chen, Yuyang Dong, Junwei Zhang, Yanyuan Huang, Siliang Wang. Tyrosine kinase inhibitor (TKI) plus PD-1 blockade in TKI-responsive MSS/pMMR metastatic colorectal adenocarcinoma (mCRC): Results of a multicenter, phase II trial (TRAP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6002.