A Phase Ib Multicenter, Open-label Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Immunotherapy Agents With and Without Chemotherapy Agents 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 (HER2) Overexpression (OE) (DESTINY-Lung03)

AstraZeneca

Summary

DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with Immunotherapy Agents with and without chemotherapy in patients with HER2 over-expressing non-small cell lung cancer. The efficacy will be also analyzed as a secondary endpoint.

Description

Part 1 is a dose escalation study by design, allowing the assessment of safety, tolerability, and recommended dose levels of the combination of T-DXd and durvalumab plus cisplatin, carboplatin, or pemetrexed. No more patients will be enrolled in this part of the study. Part 2, expansions in the treatment-naïve setting on any recommended dose level, will not be initiated. The evaluation of T-DXd combination treatment with immunotherapy continues in Part 3, Part 4, and Part 5. In Part 3, T-DXd is assessed in combination with volrustomig, with carboplatin (Arm 3B) or without carboplatin (Arm 3A)…

Eligibility

Age range: 18+ years
Sex: All
Healthy volunteers: No

Detailed criteria

Inclusion criteria: * Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC * Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting. * Part 3, Part 4 and Part 5: Patients must have tumors that do not harbor known genomic alterations or actionable driver kinases, for which approved therapies are available are allowed. * Part 3, Part 4 and Part 5: Patient must be treatment-naïve for advanced or metastatic NSCLC. Patients who have received prior adjuvant, or neoadjuvant chemotherapy, or definitive chemoradiation for advance…

Interventions

Drug
T-DXd
T-DXd: administered as an IV infusion
Biological
Durvalumab
Durvalumab: administered as an IV infusion
Drug
Cisplatin
Cisplatin: administered as an IV infusion
Drug
Carboplatin
Carboplatin: administered as an IV infusion
Drug
Pemetrexed
Pemetrexed: administered as an IV infusion (drug not used)
Drug
Volrustomig
Volrustomig: administered as an IV infusion
Drug
Rilvegostomig
Rilvegostomig: administered as an IV infusion

Locations (91)

Research Site
Duarte, California
Research Site
Newport Beach, California
Research Site
Orange, California
Research Site
Santa Rosa, California
Research Site
Westwood, Kansas
Research Site
Baltimore, Maryland