Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC - DL03

Study identifier:D967YC00001

ClinicalTrials.gov identifier:NCT04686305

EudraCT identifier:2020-003260-31

CTIS identifier:N/A

Recruiting

Official Title

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)

Medical condition

Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Phase

Phase 1

Healthy volunteers

Study drug

T-DXd, Cisplatin, Carboplatin, Pemetrexed, MEDI5752

Sex

All

Estimated Enrollment

168

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 09 Mar 2021

Estimated Primary Completion Date: 23 Dec 2025

Estimated Study Completion Date: 23 Dec 2025

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2024 by AstraZeneca

Collaborators

Daiichi Sankyo, Inc.

Inclusion and exclusion 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: Treatment-naïve for non curative treatment for locally advanced or metastatic NSCLC.
- Part 3: Patients must have tumors without known genomic alterations or actionable driver kinases, as determined by existing local test results, for which approved therapies are available are allowed. Patients who received prior adjuvant, neoadjuvant chemotherapy, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred > 6 months from end of last therapy
- HER2overexpression 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
- Part 3: Minimum body weight of 35 kg.

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 (positive hepatitis B virus surface antigen or hepatitis B virus core antibody) or hepatitis 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
- Cardiomyopathy of any etiology, symptomatic CHF (as defined by New York Heart Association Class > II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia (Part 3).
- A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or CART (Concentrated Ascites Reinfusion Therapy)
- Unresolved toxicities not yet resolved to Grade ≤ 1 or baseline from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.
- must not have any medical contraindication to platinum-based chemotherapy.
- Part 3 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting.

Sort by status

No locations available

Arms	Assigned Interventions
Experimental: Arm 1A: T-DXd, Durvalumab and Cisplatin T-DXd, Durvalumab and Cisplatin	Drug: T-DXd T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Cisplatin Cisplatin: administered as an IV infusion
Experimental: Arm 1B: T-DXd, Durvalumab and Carboplatin T-DXd, Durvalumab and Carboplatin	Drug: T-DXd T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Carboplatin Carboplatin: administered as an IV infusion
Experimental: Arm 1C: T-DXd, Durvalumab and Pemetrexed T-DXd, Durvalumab and Pemetrexed (Arm not initiated)	Drug: T-DXd T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Pemetrexed Pemetrexed: administered as an IV infusion (drug not used)
Experimental: Arm 1D: T-DXd T-DXd	Drug: T-DXd T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan
Experimental: Arm 3A: T-DXd and MEDI5752 Drug: T-DXd and MEDI5752 T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: MEDI5752 MEDI5752: administered as an IV infusion Other Name: Volrustomig	Drug: T-DXd T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Drug: MEDI5752 MEDI5752: administered as an IV infusion Other Name: Other Name: Volrustomig
Experimental: Arm 3B: T-DXd, MEDI5752 and Carboplatin Drug: T-DXd, MEDI5752 and Carboplatin T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: MEDI5752 MEDI5752: administered as an IV infusion Other Name: Volrustomig Drug: Carboplatin Carboplatin: administered as an IV infusion	Drug: T-DXd T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Drug: Carboplatin Carboplatin: administered as an IV infusion Drug: MEDI5752 MEDI5752: administered as an IV infusion Other Name: Other Name: Volrustomig

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]