Study objectives and endpoints
death, tumor, SD, PD, mTNBC
DISEASE PROGRESSION, TUMOR, DISEASE, SECONDARY, DISEASE
Primary objective was to evaluate the clinical benefit (CB; complete response [CR] + partial response [PR] + stable disease [SD]) of adding the anti-CD73 antibody oleclumab to the combination of paclitaxel, carboplatin with durvalumab in previously untreated, locally recurrent inoperable or mTNBC patients by comparing the clinical benefit rate (CBR) after 24 weeks from the first dose of study drug administration between patients treated with or without oleclumab.Secondary objectives were the following: (1) to compare the objective response rate (ORR; complete response [CR] + partial response [PR]) and the duration of response (DOR) between patients treated with or without oleclumab; (2) to compare PFS and overall survival (OS) between patients treated with or without oleclumab; (3) to evaluate the safety of the treatment combination; (4) to evaluate the efficacy of oleclumab in combination with paclitaxel, carboplatin and durvalumab according to PD-L1 and CD73 status.Initial disease status was evaluated by imaging studies (contrast-enhanced CT scan and/or MRI of chest, abdomen and pelvis) during the screening phase. Disease status was followed by imaging studies at weeks 8 (±3 days), 16 (±3 days), and 24 (±3 days) after the start of treatment. Thereafter, imaging was performed every 12 weeks (±3 days; contrast-enhanced CT scan or MRI) regardless of any treatment delays. Patients who stopped all study treatments for reasons other than PD continued post-treatment imaging studies for efficacy follow-up until verified PD, start of a new anticancer treatment, withdrawal of consent to study participation, death, or end of the study (whichever came first).Patients experiencing PD at week 8 or week 16, as defined by RECIST v1.1, could continue the study treatment in case of good clinical condition assessed by a stable or even improved ECOG performance status, to avoid treatment discontinuation in case of pseudo-progression. If the following assessment of tumor burden (8 weeks later) confirmed PD (as defined by RECIST), study treatment was discontinued.The primary endpoint was the clinical benefit, defined as the achievement of CR or PR or demonstrated SD at 24 weeks from the first dose of study treatment based on the RECIST v1.1.The secondary endpoints were the following: (1) Objective Response. OR was defined as achieving a CR or PR as the best overall response (BOR) based on RECIST v1.1; (2) Duration of Response. DOR is defined as the time from documentation of the first tumor response to disease progression based on RECIST v1.1; (3) Progression-Free Survival. PFS was defined as the time from the first study drug administration to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurs first. Patients who were alive and progression-free at the time of analysis were censored at the time-point of their last tumor assessment by imaging; (4) Overall Survival. OS was defined as the time from the first study drug administration to death due to any cause. Patients without documented death at the time of the analysis were censored at the date of the last follow-up; (5) Frequency, duration, and severity of AEs based on CTCAE 5.0.