April 2025
Cancer Research
Background OBT076 is a novel ADC (payload DM4) targeting CD205. Preclinical studies demonstrated potent antitumor activity. This open label Phase 1B study (Part C) aimed to evaluate the safety and preliminary efficacy of sequential therapy OBT076 followed by anti-PD-1 balstilimab in patients with CD205 positive (2+ in ≥ 50% by IHC) solid tumors. Methods Key eligibility criteria included age ≥ 18, CD205 positivity, ECOG ≤1, and progression on/after standard treatments. Patients received up to 3 cycles of OBT076 at 3.0 mg/kg intravenously Q3W followed by balstilimab 3.0 mg/kg intravenously Q2W until progression or toxicity. Primary endpoints were safety and tolerability, while secondary endpoints were overall response rate (ORR), disease control rate (DCR), and progression free survival (PFS). Results At data cut-off of 18-Dec-2024, a total of 20 patients (pts) received at least one dose of OBT076 in Part C, 13 pts (65%) switched to balstilimab after median of 2.0 cycles [1;4]. 5 pts switched already after 2 cycles due to Adverse event (AE)/progression of disease (PD). Median age was 57.5 years [33;78], 40% male, 60% female, pts received median of 2.0 [1;6] prior lines of therapy. Most common tumor types enrolled included ovarian cancer (7 pts, 35%), Adenoid cystic carcinoma (4 pts, 20%), gastric/esophageal/GEJ cancer (4 pts, 20%) and NSCLC (2 pts, 10%). Safety The most common AEs during treatment with OBT076 were neutropenia (60%), febrile neutropenia (50%), anemia (65%), diarrhea (55%), and fatigue (40%). Two patients reported potentially immune-related AE during balstilimab (Grade 1 TSH increase, Grade 2 hypothyroidism). Grade 3-4 AEs occurred in 95% of pts, with neutropenia (50%), febrile neutropenia (50%, all Grade 3) and anemia (20%) being the most frequent Grade 3-4 events. Febrile neutropenia resolved quickly in most of the cases after empiric antibiotic therapy, in the majority of cases not associated with severe infections. Dose delays of OBT076 were required in 20% (4/20) of pts, dose reductions were required in 20% (4/20) of pts due to neutropenia, and 40% (8/20) discontinued treatment due to AEs. There were no treatment-related deaths. Efficacy Best response was partial response (PR) in 2 pts, stable disease (SD) in 6 pts, progression of disease (PD) in 8 pts, assessment missing in 4 pts. Both patients with PR (GEJ cancer and bladder cancer, respectively) were anti-PD-1 naïve and had CPS/TPS < 10/10%. Disease control rate was 40% (8/20). Median PFS for pts with ovarian cancer was 2.2 months, 1.7 months for pts with ACC, 2.0 months for pts with gastric/esophageal/GEJ cancer. Conclusions OBT076 demonstrated manageable safety profile, neutropenia and febrile neutropenia were the most frequent Grade 3-4 AEs. No clinically relevant ocular events have been reported. Preliminary activity with PRs was seen in GEJ cancer and bladder cancer. Insufficient activity in terms of PFS prolongation does not support further investigation of sequential short-course OBT076 followed by checkpoint inhibitors. Citation Format Lauriane Eberst, Daniel Flora, Cécile Vicier, Rita Saude Conde, Harald Haeske, Andrew Dickinson, Chloe Nicholson, Christian Rohlff, Yu-Tzu Tai, Clément Dumont. Preliminary activity and safety of OBT076 in patients with CD205 positive solid tumors: Results from the phase 1b part C sequential expansion cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT043.
