Phase 1 Study Evaluating Safety of Trastuzumab Deruxtecan with Immunotherapy and Chemotherapy in Advanced or Metastatic HER2-Positive Non-Squamous Non-Small Cell Lung Cancer

What this Trial Is About

Researchers are evaluating the safety and tolerability of trastuzumab deruxtecan T-DXd combined with immunotherapy agents, with or without chemotherapy, in patients who have HER2 over-expressing non-small cell lung cancer NSCLC. This phase Ib study focuses on advanced or metastatic non-squamous NSCLC patients, aiming to understand optimal dosing and safety profiles. The study is sponsored by AstraZeneca and includes multiple study parts to explore different drug combinations and regimens. The trial includes several parts Part 1 involved dose escalation of T-DXd with durvalumab plus cisplatin, carboplatin, or pemetrexed Parts 3, 4, and 5 assess combinations of T-DXd with volrustomig or rilvegostomig, with or without carboplatin, in various dosing schedules. Patients receive the study drugs as intravenous infusions. Some parts involve randomization between arms with or without carboplatin, focusing on dose optimization in first-line treatment settings. Enrollment in some parts is closed, while others continue to explore safety and efficacy. Participants undergo regular assessments including tumor measurements by RECIST 1.1, organ and bone marrow function tests, and monitoring of adverse events for about 20 months. The study measures safety outcomes like frequency of adverse events and serious adverse events, and secondary outcomes such as response rate, duration of response, disease control, progression-free survival, overall survival, and pharmacokinetics of the drugs. Immunogenicity of the treatments is also evaluated. Participants must have measurable disease and meet performance status criteria, with follow-up to assess treatment effects and safety.

Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC