WCLC 2025 - Posters & ePosters-P3.13.13 A Phase II Study of Vobramitamab Duocarmazine in Patients With Relapsed or Refractory Extensive-Stage Small-Cell Lung Cancer

P3.13.13 A Phase II Study of Vobramitamab Duocarmazine in Patients With Relapsed or Refractory Extensive-Stage Small-Cell Lung Cancer

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Pdf Summary

This phase II study evaluated vobramitamab duocarmazine (MGC018), an antibody-drug conjugate targeting B7-H3, in patients with relapsed or refractory extensive-stage small-cell lung cancer (ES-SCLC). B7-H3 is highly expressed in SCLC tumors and is a promising immunotherapy target due to its limited presence in normal tissues.<br /><br />The trial enrolled nine patients with ES-SCLC who had previously received platinum-based chemotherapy. Patients received vobramitamab duocarmazine intravenously every 28 days, initially at 2.7 mg/kg; the dose was later reduced to 2.0 mg/kg due to observed treatment-related adverse events (TRAEs) in other studies. The primary endpoint was overall response rate (ORR) by RECIST v1.1; secondary endpoints included safety, duration of response, progression-free survival (PFS), and overall survival (OS). Exploratory analyses examined B7-H3 expression in tumor tissue and plasma extracellular vesicles (EVs).<br /><br />Results showed limited efficacy: no objective responses occurred, leading to early trial termination after the first stage. Median PFS was 2.0 months, and median OS was 4.3 months. One patient achieved stable disease for eight treatment cycles. Treatment was associated with several TRAEs, primarily grade 1-2 anemia, anorexia, fatigue, conjunctivitis, neutropenia, rash, and thrombocytopenia. One grade 4 neutropenia and several grade 3 adverse events, including pneumonia, were reported.<br /><br />B7-H3 immunohistochemistry intensity in tumor tissue may correlate with disease control, suggesting it could serve as a biomarker. Ongoing analyses are assessing plasma EV B7-H3 levels for correlation with efficacy.<br /><br />While vobramitamab duocarmazine showed limited activity in this setting, B7-H3 remains an appealing target in SCLC. Early-phase trials of other B7-H3-targeting ADCs have reported higher response rates (~58-63%), indicating that further exploration is warranted. Future research should focus on optimizing the cytotoxic payload, dosing strategies, and identifying biomarkers predictive of response or resistance to B7-H3-directed therapies in ES-SCLC.

Asset Subtitle

Tina Roy

Meta Tag

Speaker Tina Roy

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

vobramitamab duocarmazine

MGC018

B7-H3

antibody-drug conjugate

extensive-stage small-cell lung cancer

ES-SCLC

phase II study

overall response rate

treatment-related adverse events

biomarkers