Vobramitamab duocarmazine, an anti–B7-H3 antibody–drug conjugate, in patients with advanced solid tumors: Final results of a phase 1 cohort expansion

IF 5.6 2区医学 Q1 ONCOLOGY

Cancer Pub Date : 2026-07-23 DOI:10.1002/cncr.70544

Eugene Shenderov MD, PhD, Manish R. Sharma MD, Elena Garralda MD, John Powderly MD, Iwona Ługowska MD, Alexander Spira MD, PhD, Marc Cucurull Salamero MD, Sekwon Jang MD, Rasha Cosman BMedSc, MBBS, FRACP, John Shen MD, Wen Xu BMedSc, MBBS, FRACP, Piotr J. Wysocki MD, PhD, Rodryg Ramlau MD, PhD, Emmanuel S. Antonarakis MD, Andrew J. Weickhardt MBBS, FRACP, DMedSc, Jakub Żołnierek MD, PhD, Emiliano Calvo MD, PhD, Enxu Zhao MS, Chet Bohac MD, Ashley Ward MD, Girish Mallesara MBBS, MD, DM, FRACP

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引用次数: 0

Abstract

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.

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Vobramitamab duocarmazine，一种抗b7 - h3抗体-药物偶联物，用于晚期实体瘤患者：1期队列扩展的最终结果

背景：Vobramitamab duocarmycin是一种正在研究的抗体-药物偶联物（ADC），靶向B7同源物3 (B7- h3)，具有基于duocarmycin的细胞毒性dna烷基化有效载荷。本研究评价了其在晚期实体瘤中的安全性和抗肿瘤活性。方法：在该1/2期临床试验（CP-MGC-018-01/NCT03729596）中，以0.5 ~ 4.0 mg/kg每3周静脉滴注的剂量评估沃布拉马单抗多卡玛嗪。多队列肿瘤扩展期主要集中在转移性去势抵抗性前列腺癌（mCRPC）、肺癌、乳腺癌、黑色素瘤和鳞状头颈部癌。主要终点是安全性和耐受性。次要终点包括药代动力学、免疫原性和抗肿瘤活性。结果：在沃布拉米单抗多卡马嗪治疗的患者中，97.9%（143例中的140例）经历了所有级别的治疗相关不良事件（TRAEs）；≥3级TRAE发生率为65.0%（143例中93例）。在接受4.0 mg/kg治疗的患者中存在两种剂量限制性毒性（4级无热性中性粒细胞减少症和3级疲劳），因此推荐的扩展剂量为3.0 mg/kg。在所有接受3.0 mg/kg治疗的患者中，≥3级TRAEs发生率为65.3%（121人中有79人），确认的客观缓解率（ORR）为7.2%（97人中有7人），中位缓解持续时间（DOR）为6.3个月。在接受3.0 mg/kg治疗的mCRPC患者中，确诊的ORR为8.3%（24例中有2例），DOR中位数为5.3个月；确诊的前列腺特异性抗原较基线缓解率下降≥50%的患者为43.9% (18 / 41)，DOR中位数为6.2个月。结论：Vobramitamab duocarmazine在各种肿瘤类型中均表现出适度的抗肿瘤活性，其中对mCRPC的活性最为明显。治疗受到毒性的限制，特别是胸腔积液和疲劳，这限制了给药时间。在一项随机2期研究（TAMARACK/NCT05551117）中，研究治疗被停止，重新关注mCRPC，该研究后来在评估了沃布拉米单抗多卡马嗪的安全性和有效性后被停止。

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来源期刊

Cancer 医学-肿瘤学

CiteScore

13.10

自引率

3.20%

发文量

480

审稿时长

2-3 weeks

期刊介绍： The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society. CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research