Phase Ib Study of the Safety of T-DXd and Durvalumab with Chemotherapy in Advanced or Metastatic HER2+ Non-squamous NSCLC - DL03

Study identifier:D967YC00001

ClinicalTrials.gov identifier:NCT04686305

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

A 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)

Medical condition

Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Phase

Phase 1

Healthy volunteers

Study drug

Trastuzumab deruxtecan, Cisplatin, Carboplatin, Pemetrexed

Sex

All

Estimated Enrollment

136

Study type

Interventional

Age

18 Years - 120 Years

Date

Study Start Date: 09 Mar 2021

Estimated Primary Completion Date: 08 Jul 2025

Estimated Study Completion Date: 08 Jul 2025

Study design

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

Verification:

Verified 01 Feb 2023 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 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.

Sort by status

No locations available

Arms	Assigned Interventions
Experimental: Arm 1A: T-DXd, Durvalumab and Cisplatin T-DXd, Durvalumab and Cisplatin	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd 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: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd 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	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Pemetrexed Pemetrexed: administered as an IV infusion
Experimental: Arm 1D: T-DXd T-DXd	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd
Experimental: Arm 2A: T-DXd, Durvalumab and Cisplatin T-DXd, Durvalumab and Cisplatin	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Cisplatin Cisplatin: administered as an IV infusion
Experimental: Arm 2B: T-DXd, Durvalumab and Carboplatin T-DXd, Durvalumab and Carboplatin	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Carboplatin Carboplatin: administered as an IV infusion
Experimental: Arm 2C: T-DXd, Durvalumab and Pemetrexed T-DXd, Durvalumab and Pemetrexed	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Pemetrexed Pemetrexed: administered as an IV infusion
Experimental: Arm 2D: T-DXd, Durvalumab T-DXd, Durvalumab	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]