Safety and efficacy of MORAb-202 in patients (pts) with platinum-resistant ovarian cancer (PROC): Results from the expansion part of a phase 1 trial.

5513 Background: MORAb-202 is an antibody-drug conjugate consisting of farletuzumab (an antibody that binds to folate receptor alpha [FRα]) paired with eribulin mesylate (a microtubule dynamics inhibitor) conjugated via a cathepsin-B–cleavable linker. The dose-escalation part of this phase 1 study confirmed antitumor activity in pts with ovarian cancer (Shimizu 2021, CCR); based on efficacy and safety, MORAb-202 0.9 mg/kg and 1.2 mg/kg Q3W were chosen as doses for the expansion part of this study in pts with PROC. Methods: The primary objective for the expansion part of this phase 1 study conducted in Japan was to define the safety and tolerability of MORAb-202. Secondary objectives included PK characterization and efficacy assessment (best overall response, objective response rate, progression-free survival, and overall survival). Eligible pts included those who had received ≤2 regimens of chemotherapy after diagnosis of PROC, had measurable disease per RECIST v1.1, and an ECOG PS of ≤1. Pts (except those with high grade serous histology) in the expansion phase were required to be FRα positive. The expansion phase began at the 0.9 mg/kg dose (Cohort 1); Cohort 2 (1.2 mg/kg) was initiated after safety assessment of Cohort 1 was completed. Tumor responses were assessed per RECIST v1.1 by investigator. Results: Twenty-four pts were treated in Cohort 1 and 21 pts were treated in Cohort 2. Grade ≥3 TEAEs occurred in 33.3% of pts in Cohort 1 and 28.6% of pts in Cohort 2. The most common TEAE was interstitial lung disease (ILD)/pneumonitis at both dose levels (Cohort 1: 37.5% [n=9; 8 with grade 1, 1 with grade 2]; Cohort 2: 66.7% [n=14; 6 with grade 1, 7 with grade 2, 1 with grade 3]). Other common TEAEs of any grade were nausea (25.0%; 33.3%), pyrexia (33.3%; 42.9%), malaise (16.7%; 28.6%), and headache (12.5%; 47.6%), in Cohorts 1 and 2, respectively. ORR was 25.0% and 52.4% in Cohorts 1 and 2, respectively (Table). Antitumor activity was observed across FRα-expression levels (<50% and ≥50%) and will be presented. Conclusions: In the PROC population, antitumor activity was seen with both the MORAb-202 0.9 mg/kg and 1.2 mg/kg doses. While pt numbers were small, efficacy was observed irrespective of FRα-expression levels. ILD/pneumonitis was the most common TEAE and was low grade in most pts. Dose optimization is ongoing to maximize the benefit/risk profile of MORAb-202. Clinical trial information: NCT03386942. [Table: see text]