Phase Ib Study of the Safety of T-DXd and Durvalumab With Chemotherapy in Advanced or Metastatic HER2+ Non-squamous NSCLC

• Status: Recruiting
• Trial end date: 2024-02-12
• Target enrollment: 0
• Participant gender: All

Summary

DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with durvalumab and chemotherapy in patients with HER2 positive advanced and metastatic non-small cell lung cancer. The efficacy will be also analyzed as a secondary endpoint.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Daiichi Sankyo, Inc.
• Treatments: Carboplatin; Durvalumab; Pemetrexed; Trastuzumab

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 2: Treatment-naïve for non curative treatment for locally advanced or metastatic NSCLC.

• Part 2: Patients must have tumors that lack activating EGFR mutations, EML4-ALK fusion or other targetable alterations. Prior adjuvant, neoadjuvant therapies are permitted if progression has occurred > 12 months from the end of last therapy

• HER2+ (IHC 3+ or IHC 2+) status as determined by central review of tumor tissue

• WHO / ECOG performance status of 0 or 1

• Measurable target disease assessed by the investigator using RECIST 1.1

• Has protocol defined adequate organ and bone marrow function

Exclusion criteria:

• HER2 mutation if previously known

• Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening

• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy

• Active primary immunodeficiency known HIV infection, or active hepatitis B or C infection

• Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals

• Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms

• Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke

• A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or CART (Concentrated Ascites Reinfusion Therapy)

• Unresolved toxicities from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.