Abstract 428P
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 clinical trials. We aim to explore the efficacy and safety of TKIs combined with PD-1 blockade in TKI-responsive pts with MSS/pMMR mCRC refractory to standard chemotherapy (±anti-VEGF/EGFR).
Methods
This Simon 2-stage design tested the null 9-months (m) PFS rate of 27.1% vs. 55% (power = 0.90; α = 0.05). If >4 of 16 pts in stage 1 has reached ≥9-m PFS, 9 more pts are enrolled. Eligible pts received 1 cycle of TKIs (fruquintinib 5mg or regorafenib 120mg, qd po, 3 weeks on/1 week off) were grouped into 3 arms determined by imaging (according to RECIST v 1.1): (a) arm A (obvious response): including reduction of target lesion diameter to CR, PR or shrunken SD, or cavitation in metastatic lung lesions, or decrease in the density of liver metastatic target lesions ≥15%; (b) arm B (general response): enlarged SD; (c) arm C (poor response): PD. Then pts in arm B were given 1 more cycle of TKIs and grouped again. After 1 or 2 cycles of TKIs, pts in arm A received TKIs plus anti-PD-1 antibody (toripalimab 240mg, i.v.gtt, q3w, until disease progression or up to 2 years), pts in arm B continued with TKIs.
Results
35 pts were enrolled as of Apr 15, 2022. Median age was 59 (34-72); 45.7% were male; all were ECOG PS 1. After TKI treatment, 14 entered arm A in 32 efficacy evaluable pts. All pts in arm A had prior 5-FU and oxaliplatin, 85.7% had prior anti-VEGF/EGFR therapies and median prior regimens were 2 (1-4). In arm A, ORR was 14.3%, 6-m, 9-m and 12-m PFS rates were 64.3% (9/14), 42.9% (6/14) and 28.6% (4/14), respectively. Both mPFS and mOS were not mature. At data cutoff, 4 pts (28.6%) were still on treatment in arm A. The most common treatment-related adverse events (TRAEs) (total; Grade ≥3) were hand-foot skin reaction (42.9%; 21.4%), hypothyroidism (42.9%; 7.1%), proteinuria (28.6%; 7.1%) and hypertension (21.4%; 21.4%). No treatment related death.
Conclusions
TKIs combined with PD-1 blockade has shown encouraging efficacy with acceptable safety in MSS/pMMR mCRC pts responsive to TKI treatment.
Clinical trial identification
NCT04483219 The start date was July 2020.
Editorial acknowledgement
Legal entity responsible for the study
Liaoning Cancer Hospital & Institute.
Funding
Shanghai Junshi biosciences Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.