DESTINY-Lung03: This phase I study is investigating how safe, tolerable and effective targeted therapy (trastuzumab deruxtecan) is alone, and in combination with immunotherapy (durvalumab) and chemotherapy (cisplatin, carboplatin or pemetrexed) in people with HER2-positive, advanced or metastatic, non-small cell lung cancerA Phase Ib Multicenter, Open-label Dose-escalation Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Durvalumab in Combination With Cisplatin, Carboplatin or Pemetrexed in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 Overexpression (HER2+) (DESTINY-Lung03)

Summary

This study will consist of two parts. Part 1 is a dose-escalation study design allowing the assessment of safety, tolerability and recommended dose levels of the combination of trastuzumab deruxtecan (T-DXd) and durvalumab plus cisplatin, carboplatin or pemetrexed. Part 1 will involve people on their second or third-line of treatment. In Part 2, expansions in the treatment naïve setting on any recommended dose level may take place to study preliminary efficacy as well. In Part 1, the dose of T-DXd and the chemotherapeutic components on Arms 1A, 1B and 1C (cisplatin, carboplatin or pemetrexed) will be modified during the dose-escalation part in order to find the recommended phase 2 dose (RP2D). The dose of durvalumab will remain fixed in this part of the study. Arm 1D will ass T-DXd as monotherapy. All treatments will be administered via an intravenous (IV) infusion. The Part 2 of the study may be initiated following Part 1, at the discretion of the sponsor.