Cancer · 2026
Vobramitamab duocarmazine, an anti-B7-H3 antibody-drug conjugate, in patients with advanced solid tumors: Final results of a phase 1 cohort expansion.
СтатьяКлиническое исследование I фазыКлиническое исследование II фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Shenderov Eugene, Sharma Manish R, Garralda Elena, Powderly John, Ługowska Iwona, Spira Alexander, Salamero Marc Cucurull, Jang Sekwon, Cosman Rasha, Shen John, Xu Wen, Wysocki Piotr J, Ramlau Rodryg, Antonarakis Emmanuel S, Weickhardt Andrew J, Żołnierek Jakub, Calvo Emiliano, Zhao Enxu, Bohac Chet, Ward Ashley, Mallesara Girish
Аннотация
BACKGROUND: Vobramitamab duocarmazine is an investigational antibody-drug conjugate (ADC) targeting B7 homolog 3 (B7-H3) with a cytotoxic duocarmycin-based DNA-alkylating payload. This study evaluated its safety and antitumor activity in advanced solid tumors.
METHODS: In this phase 1/2 trial (CP-MGC-018-01/NCT03729596), vobramitamab duocarmazine was evaluated at 0.5-4.0 mg/kg intravenously every 3 weeks. The multicohort tumor-expansion phase focused on metastatic castration-resistant prostate cancer (mCRPC), lung, breast, melanoma, and squamous head and neck carcinomas. Primary end points were safety and tolerability. Secondary end points included pharmacokinetics, immunogenicity, and antitumor activity.
RESULTS: Across vobramitamab duocarmazine-treated patients, 97.9% (140 of 143) experienced treatment-related adverse events (TRAEs) of all grades; the grade ≥3 TRAE rate was 65.0% (93 of 143). With two dose-limiting toxicities in patients receiving 4.0 mg/kg (grade 4 afebrile neutropenia and grade 3 fatigue), the recommended dose for expansion was 3.0 mg/kg. Among all patients treated at 3.0 mg/kg, the rate of grade ≥3 TRAEs was 65.3% (79 of 121) and the confirmed objective response rate (ORR) was 7.2% (seven of 97), with a 6.3-month median duration of response (DOR). Among patients with mCRPC receiving 3.0 mg/kg, the confirmed ORR was 8.3% (two of 24), with a 5.3-month median DOR; the confirmed prostate-specific antigen with a ≥50% decline from the baseline response rate was 43.9% (18 of 41), with a 6.2-month median DOR.
CONCLUSIONS: Vobramitamab duocarmazine demonstrated modest antitumor activity across tumor types, with the most pronounced activity in mCRPC. Treatment was limited by toxicity, particularly pleural effusions and fatigue, which restricted dosing duration. Study treatment was discontinued to refocus on mCRPC in a randomized phase 2 study (TAMARACK/NCT05551117), which was later discontinued after assessment of the vobramitamab duocarmazine safety and efficacy profile.
METHODS: In this phase 1/2 trial (CP-MGC-018-01/NCT03729596), vobramitamab duocarmazine was evaluated at 0.5-4.0 mg/kg intravenously every 3 weeks. The multicohort tumor-expansion phase focused on metastatic castration-resistant prostate cancer (mCRPC), lung, breast, melanoma, and squamous head and neck carcinomas. Primary end points were safety and tolerability. Secondary end points included pharmacokinetics, immunogenicity, and antitumor activity.
RESULTS: Across vobramitamab duocarmazine-treated patients, 97.9% (140 of 143) experienced treatment-related adverse events (TRAEs) of all grades; the grade ≥3 TRAE rate was 65.0% (93 of 143). With two dose-limiting toxicities in patients receiving 4.0 mg/kg (grade 4 afebrile neutropenia and grade 3 fatigue), the recommended dose for expansion was 3.0 mg/kg. Among all patients treated at 3.0 mg/kg, the rate of grade ≥3 TRAEs was 65.3% (79 of 121) and the confirmed objective response rate (ORR) was 7.2% (seven of 97), with a 6.3-month median duration of response (DOR). Among patients with mCRPC receiving 3.0 mg/kg, the confirmed ORR was 8.3% (two of 24), with a 5.3-month median DOR; the confirmed prostate-specific antigen with a ≥50% decline from the baseline response rate was 43.9% (18 of 41), with a 6.2-month median DOR.
CONCLUSIONS: Vobramitamab duocarmazine demonstrated modest antitumor activity across tumor types, with the most pronounced activity in mCRPC. Treatment was limited by toxicity, particularly pleural effusions and fatigue, which restricted dosing duration. Study treatment was discontinued to refocus on mCRPC in a randomized phase 2 study (TAMARACK/NCT05551117), which was later discontinued after assessment of the vobramitamab duocarmazine safety and efficacy profile.