Analysis of phase I clinical trials (Ph1-CT) new enrollment patterns in the immuno-oncology era.

Abstract

e14549 Background: Immuno-Oncology (IO) has revolutionized anticancer therapeutics and changed the early drug development paradigm. Positive results and limited access to IO drugs in some countries have led to increased enrollment in IO Ph1-CT at an earlier timepoint in patients (pts) disease journey. We evaluated the impact of IO era on enrollment patterns in Ph1-CT. Methods: We retrospectively reviewed pts with recurrent/metastatic solid tumors enrolled in Ph1-CT from January 2018 to June 2021 at the Phase 1 Unit of Catalan Institute of Oncology (ICO), Barcelona, Spain. The primary goal was to assess Ph1-CT enrollment patterns, including use of molecular pre-screening/personalized drug matching, and the availability of alternative standard of care (SOC). Overall response rate (ORR) was assessed according to RECIST 1.1. Clinical benefit rate (CBR) was defined as complete/partial response+stable disease for ≥6 months. Median progression-free survival (mPFS) and overall survival (mOS) using Kaplan-Meier method were provided. Results: A total of 175 pts were enrolled in Ph1-CT. Median age was 54 years (range 43-75), Male:Female = 99:76, 99% had ECOG 0-1. The most prevalent tumors were: 32 (18%) breast, 31 (18%) colorectal, 25 (14%) urogenital and 23 (13%) glioblastoma multiforme. One hundred forty-six (83%) pts were enrolled in Ph1-CT with IO (alone or in combination) and 29 (17%) pts with targeted therapy (TT). Molecular pre-screening tests were required in 24 (14%) pts (22 pts IO vs 2 pts TT trial). Eleven (42%) pts were pre-screening failures. Screening failure (SF) rate was 19%, the main reason being clinical worsening for 7 (4%) pts. Thirty-three (19%) pts had an alternative SOC treatment available at time of enrollment. One hundred two (58%) pts had received ≤1 prior lines and 26 (89%) were IO-naïve. Finally, 129 (74%) out of 175 pts enrolled were treated within Ph1-CT. Out of 129 treated pts, ORR was achieved in 18 (14%) pts (3% complete response) and 44 (34%) had stable disease. CBR was observed in 36 (28%) pts. mPFS was 2.8 months and mOS was 10.9 months. Toxicity grade 3-4 occurred in 25 (19%) of pts and 6 (5%) pts had to interrupt treatment. Seventy-one (55%) pts received subsequent therapies: 22 (17%) in Ph1-CT; 49 (38%) SOC. Eleven (9%) pts received IO as subsequent therapy. Decline in ECOG status (baseline vs end of treatment) occurred in 65 (50%) pts. Conclusions: In our cohort of Ph1CT pts, there has been an increasing number of pts enrolled in IO trials compared to TT. Most pts received treatment within Ph1-CT at an earlier timepoint in the course of their disease (1st or 2nd lines). Our results suggest a clear impact of the IO era on the trends of Ph1-CT availability and enrollment patterns.