491P - Clinical benefit and response rate in early phase clinical trials: First report from a single-institution study

Abstract

BackgroundPhase I clinical trials (Ph1) are crucial in the development of new anticancer therapies. New generation Ph1 investigating novel classes of drugs led to consistent improvements in response rates and clinical benefit in enrolled patients (pts). The aim of our study is to evaluate pts enrolled in Ph1 testing targeted therapies (TT), immunotherapy (IT), and their combinations. MethodsData of pts screened for enrollment in Ph1 in our institution were retrieved from clinical records. Primary objectives of the study were to determine overall response rate (ORR) and clinical benefit rate (CBR), according to RECIST 1.1 or iRECIST criteria (if applicable). Logistic regression analysis was performed to evaluate the impact of different variables on ORR and CBR. ResultsFrom December 2014 to November 2018, 723 pts were screened [median age 57 years (22-82)]. Primary tumor locations included breast (27.7%), biliary tract (15.5%), pancreas (8.9%), lung (6.8%), colorectal (6.5%), and ovary (4.8%). 275/723 (38.0%) pts had >2 metastatic sites; 304/723 (42.0%) received >2 lines of treatment in the metastatic setting. 481 patients (66.5%) resulted screen failure, mainly due to the absence of druggable molecular alteration(s) for biomarker- driven Ph1 (56.1%), abnormal lab results (12.7%), or poor performance status (11.4%). Conversely, the 242 (33.5%) eligible pts received IT (47.5%), TT (48.3%), or IT+TT combinations (4.2%). At time of data analysis, 209 (88.6%) patients experienced disease progression. ORR and CBR were 14.8% and 28.0%, respectively. No differences were found per age (</>70y), sex or drug class. Pts with ≤2 metastatic sites had a higher CBR (OR 2.67, 95%, CI 1.39-5.10; Wald test p=.003), while pts who received ≤2 lines of treatment in the metastatic setting presented with higher ORR (OR 2.37; 95%, CI 1.03-5.44; Wald test p=.004). ConclusionsOur results confirmed the consistent improvement in terms of CBR and ORR of the new generation Ph1 as compared to historical reported data. Better outcomes were observed in less pre-treated pts with lower burden of disease, suggesting that Ph1 should be proposed in earlier lines of therapy to derive a greater benefit. Further analyses on a larger cohort of Ph1 patients are currently ongoing. Legal entity responsible for the studyIstituto Europeo di Oncologia. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.