Outcomes of patients (pts) treated with novel immunotherapy (IT) agents in phase 1 clinical trials (Ph1-CT) at early lines for advanced disease.

2581 Background: The overall survival (OS) benefit observed with immune checkpoint inhibitors led to their approval in many tumor types. Given the large number of IT compounds in early clinical development, many pts are offered IT within Ph1-CT even before having exhausted standard of care (SOC) therapies. We assessed outcomes of pts receiving novel IT treatments within Ph1-CT at the Phase 1 Unit of Catalan Institute of Oncology (ICO), Barcelona, Spain. Methods: We retrospectively reviewed a correlative series of pts with advanced/metastatic solid tumors treated with IT within Ph1-CT at ICO from January 2018 to June 2021. Primary endpoint was to assess clinical outcomes measured by median progression-free survival (mPFS) and median OS (mOS) according to number of prior lines (PL) for recurrent/metastatic disease, grade 3-4 toxicity (G3-4 Tox) and age. Data on prior IT (yes vs no) and availability of alternative SOC were evaluated. 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 (m). PFS/OS were calculated by Kaplan-Meier method. Log-rank test was used for comparisons. Median PFS of alternative SOC according to historical data was recorded by tumor type and line of treatment. Results: A total of 104 pts received IT within Ph1-CT: IT monotherapy = 39 (37.5%), IT combinations = 65 (62.5%) (IT+IT = 59 [90.8%], IT+targeted therapy = 6 [9.2%]). Median age was 54 y (42-77), 62.5% were men and all had ECOG 0-1. Four most frequent cancers were urothelial (19.2%), colorectal (15.3%), head & neck (12.5%) and glioblastoma (11.5%). Number of PL: 0 = 20 (19.2%) pts, 1 = 37 (35.6%) pts, ≥2 = 47 (45.2%) pts. Nine (8.6%) pts had received prior IT. G3-4 Tox rate for the overall population was 19.2% and for pts who had received prior IT was 33%. ORR was 11.5%; CBR was 24%. Overall mPFS and mOS were 2.7m and 8.6m, respectively. Pts with less PL had greater mPFS and mOS (p < 0.05) (Table). Pts with available alternative SOC had lower mPFS but similar mOS compared to historical SOC (2.6m vs 4.8m, 11.4m vs 11.8m, respectively). G3-4 Tox (yes vs no) and age ( < 70 vs ≥70) did not significantly impact on mOS or mPFS (p = 0.18 and p = 0.83, respectively). At end of Ph1-CT treatment, 47 (45.2%) pts worsened their ECOG status, 15 (14.4%) pts were enrolled in a subsequent trial and 22 (21.1%) pts received SOC. Conclusions: In our cohort of pts treated with novel IT within Ph1-CT, overall clinical outcomes were modest in terms of mPFS, mOS, and CBR. However, pts with less pre-treated tumors seem to achieve higher survival benefit from early treatment with IT within Ph1-CT, although this benefit remains unclear in pts with alternative SOC. [Table: see text]