Abstract 1375P
Background
Advanced GC pts have limited treatment options and poor prognosis. Immune checkpoint inhibitors (ICIs) showed promising activities in pretreated pts, especially for those with high PD-L1 expression. Blockade of TGF-β pathway may enhance the tumor response to ICIs.
Methods
This phase I study composed of a dose escalation and expansion (ESC & EXP) period in solid tumors and multiple clinical expansion cohorts. Based on findings of the ESC & EXP period, 30 mg/kg Q3W was determined as RP2D. In the GC clinical expansion cohort, pts who had progressed on or were intolerant to ≤2L standard therapies were given SHR-1701 at the RP2D. Prior ICIs were not allowed. Primary endpoint was ORR per RECIST v1.1.
Results
35 pts were enrolled: stage IV, 91.4%; 2L prior systemic therapies, 54.3%. By Apr 6, 2021, median SHR-1701 exposure was 12.0 wk (range 3.0-64.9). Of the 31 pts with post-baseline scan(s), 16 (51.6%) pts showed tumor shrinkage. 1 CR and 7 PR were achieved, and ORR was 25.8% (95% CI 11.9-44.6). 2 PR were not confirmed yet as there was no consequent scan after first PR as of data cutoff. Confirmed ORR was 19.4% (95% CI 7.5-37.5; 1 CR + 5 PR; ongoing responses: 66.7% [4/6]). DCR was 41.9% (95% CI 24.5-60.9). CBR (CR + PR + SD≥23 wk) was 25.8% (95% CI 11.9-44.6). Median PFS was 1.4 mo (95% CI 1.3-9.6), and 6-mo PFS rate was 38.7% (95% CI 22.0-55.1). Median OS was not reached yet. Exploratory analyses showed a trend towards favourable responses for pts with a PD-L1 CPS ≥5 (Table). Most common TRAEs (incidence >10% in 35 pts) were rash, increased AST/ALT, decreased FT3 and pruritus. Incidence of irAEs was 45.7%. Grade 3 or 4 TRAEs occurred in 17.1% of pts, and no pts died due to TRAEs. Incidence of grade ≥3 irAEs was 11.4%. Table: 1375P
Efficacy outcomes* in all patients and subgroups by PD-L1 expression
| All patients (N=31) | CPS <5 (N=10) | CPS≥5 (N=9) | |
| ORR, n (%; 95% CI) | 6 (19.4%; 7.5-37.5) | 1 (10.0%; 0.3-44.5) | 4 (44.4%; 13.7-78.8) |
| DCR, n (%; 95% CI) | 13 (41.9%; 24.5-60.9) | 3 (30.0%; 6.7-65.2) | 4 (44.4%; 13.7-78.8) |
| CBR, n (%; 95% CI) | 8 (25.8%; 11.9-44.6) | 2 (20.0%; 2.5-55.6) | 4 (44.4%; 13.7-78.8) |
| Median PFS (95% CI), mo | 1.4 (1.3-9.6) | 1.4 (1.2-7.5) | 1.4 (0.4-9.8) |
| 6-mo PFS rate, % (95% CI) | 38.7% (22.0-55.1) | 30.0% (7.1-57.8) | 44.4% (13.6-71.9) |
*CR and PR were confirmed.
Conclusions
SHR-1701 showed encouraging antitumor activity and manageable safety profile in pretreated r/r GC pts. PD-L1 might be a prognostic factor for SHR-1701, which needs further investigation.
Clinical trial identification
NCT03710265 Release date: Oct 18, 2018.
Editorial acknowledgement
Legal entity responsible for the study
Jiangsu Hengrui Medicine, China.
Funding
Jiangsu Hengrui Medicine, China.
Disclosure
X. Zhang: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Medicine. L. Wang: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Medicine. P. Liu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Medicine. All other authors have declared no conflicts of interest.