Clinical outcomes in phase 1 clinical trials (Ph1-CT) when treating patients (pts) with novel immunotherapy (IT) agents at early lines for advanced disease

2586 Background: Cancer pts can be offered IT drugs within Ph1-CT before having exhausted standard of care (SoC) therapies. However, whether this strategy may improve pts’ outcomes remains unclear. We assess the benefits of receiving novel IT compounds within Ph1-CT at early lines for advanced disease. Methods: We retrospectively reviewed a correlative series of pts with advanced solid tumors treated with IT within Ph1-CT at the Phase 1 Unit of Catalan Institute of Oncology (ICO), Barcelona, Spain, from January 2018 to July 2022. Primary aim was to assess clinical outcomes measured by median progression-free survival (mPFS) and median overall survival (mOS) according to number of prior lines (PL) for recurrent/metastatic disease, prior IT, availability of alternative SoC in our country, IT biomarker-selected population and grade 3-4 toxicity (G3-4 Tox) by multivariate analysis (MVA). Overall response rate (ORR) was evaluated by 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. MVA was performed by Cox regression. Results: A total of 228 pts were assessed: IT monotherapy = 49 (21.5%), IT combinations = 179 (78.5%) (IT+IT = 111 [48.7%], IT+targeted therapy = 24 [10.5%], IT+others = 44 [19.3%]). Forty-nine (21.5%) pts were included according to IT biomarkers (PDL1, TIM3 expression, MSI-H, others). Median age was 62 y (24-83), 62.7% were men. All pts had ECOG ≤1. The 4 most frequent cancer types were HNSCC (19.7%), NSCLC (15.4%), glioblastoma (10.5%) and urothelial (10.1%). Number of PL: 0 = 33 (14.5%) pts, 1 = 92 (40.3%) pts, ≥2 = 103 (45.2%) pts. Sixty-three (27.6%) pts had received prior IT and 159 (69.7%) had alternative available SoC. Overall G3-4 Tox rate was 21.5% (20.6% in pts IT-treated). ORR and CBR were higher in pts IT-naïve than in pts IT-treated (21.2% vs 12.7% [p .18] and 35.7% vs 25.4% [p .26], respectively). With a median follow-up of 19m, overall mPFS and mOS were 3.5m (2.7-3.9) and 9.8m (8.5-11.5), respectively. In the MVA, lesser number of PL, SoC availability and biomarker selection positively impacted on mOS. After Ph1-CT treatment, 111 (48.7%) pts received further treatment: 19.3% within clinical trial, 29.4% with SoC. Conclusions: In our cohort of pts treated within IT Ph1-CT, those with less PL of treatment, with available alternative SoC and/or selected by biomarker achieved higher PFS and OS. These results suggest that treating pts with novel IT agents at early lines might positively impact on survival. [Table: see text]