96P - Tyrosine kinase inhibitor (TKI) plus PD-1 blockade in TKI-responsive MSS/pMMR metastatic colorectal adenocarcinoma (mCRC): Updated results of TRAP study

Background

PD-1 blockade alone in heavily treated MSS/pMMR mCRC patients (pts) is ineffective. PD-1 blockade combined with antiangiogenic therapy has synergistic effects and has shown clinical benefits in several trials. TRAP aims to explore the efficacy and safety of TKIs combined with PD-1 blockade in TKI-responsive MSS/pMMR mCRC pts refractory to standard chemotherapy with or without anti-VEGF and/or anti-EGFR therapies. Here we report the updated results at the data cutoff of Feb 6, 2023.

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

49 pts were enrolled. Median age, 59 (34-72); male, 51.0%; ECOG PS 1, 100%; median prior regimens, 2 (1-4). 20 entered arm A in 46 evaluable pts. All pts in arm A had prior 5-FU and oxaliplatin, 85.0% had prior anti-VEGF and/or anti-EGFR therapies. In arm A, ORR was 15.0%, median follow-up was 21.6m, mPFS was 13.2m (95% CI, 8.95m-NA), 6-m, 9-m and 12-m PFS rates were 88.8% (95%CI, 75.3%-100%), 66.6% (95%CI, 46.2%-96.0%) and 50.8% (95%CI, 29.9%-86.0%). OS was not mature. 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.

Clinical trial identification

NCT04483219.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.