141P - Early phase trials outcomes in refractory upper GI cancers: A 10-year analysis from the SCRI UK phase I unit

Background

Patients with unresectable upper GI cancers have limited therapies and a dismal prognosis. While granting access to additional treatments, enrollment in phase I trials offers unclear benefits in this population.

Methods

Individual patient data of subjects with advanced upper GI cancers receiving ≥1 dose of the study drug within phase I trials at SCRI UK between 2011-2023 were collected. Objective response rate (ORR: CR+PR), clinical benefit rate (CBR: % with any tumor shrinkage), and disease control rate (DCR: CR+PR+SD) were assessed by RECIST v1.1, and progression-free survival (PFS) and overall survival (OS) from trial start. Outcomes were reported using descriptive statistics and uni- and multivariate analyses. Subjects participating in more than one trial (n=20) were assessed separately in each study.

Results

Of 1796 patients screened, 104 patients with upper GI cancers (65% esophageal/junctional; 35% gastric) from 35 phase I trials were included. Most were male (75%), had adenocarcinoma (91%), and stage IV at diagnosis (73%). At trial entry, median age was 61 (range 20-86), median number of prior lines 2 (range 1-4), and median number of metastatic sites 2 (range 1-5). Seventy-four (60%), 37 (30%), and 13 (10%) received immunotherapy (IO), small molecules, or antibody-drug conjugates, respectively; 27 (22%) received a molecularly matched therapy. Median follow-up was 14.8 months (95% CI, 10.39-68.15). ORR was 17% (95% CI, 0.10-0.26), CBR 43% (95% CI, 0.33-0.53), and DCR 87% (95% CI, 0.79-0.93) across all trials. Efficacy was comparable by number of prior lines, trial drugs, or allocation to matched therapy. In response-evaluable patients across all trials (n=100), median OS and PFS were 12.3 (95% CI, 7.77-16.88) and 2.9 months (95% CI, 2.45-3.40), respectively, and were significantly longer for responders versus non-responders (both p<0.001). Depth of response, low metastatic burden (≤2 sites), and IO combos remained significant predictors of improved survival in multivariate analysis.

Conclusions

Participation in phase I trials offers substantial benefits in refractory upper GI cancers regardless of biomarker selection with compelling results in late-line settings and potential early access to newly approved therapies.

Clinical trial identification

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.