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:2023-504949-31-00

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, Volrustomig, Rilvegostomig

Sex

All

Estimated Enrollment

244

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 Nov 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 and 4: 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 and 4: Patient must be treatment-naïve for advanced or metastatic NSCLC. Patients who have received prior adjuvant, or 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 and part 4: 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 chronic and resolved hepatitis B (positive hepatitis B virus surface antigen [HBsAg+ve] or hepatitis B virus core antibody (anti-HBc +ve) regardless of HBV DNA level)) or hepatitis C infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to treatment assignment if required by local regulations or IRB/EC
- 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
- For Part 3 and Part 4: 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 are to be excluded. Patients with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before treatment assignment to rule out acute cardiopulmonary events.
- Ascites or pericardial effusion that requires drainage, peritoneal shunt, Pleuroperitoneal shunt or CART (Concentrated Ascites Reinfusion Therapy)
- For Part 3 and Part 4: Active non-infectious skin disease (including any grade rash, urticarial, dermatitis, ulceration, or psoriasis) requiring systemic treatment, active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
- 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 and 4 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.
-For Part 3 and Part 4: History of substance abuse or any other medical or psychological conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
-For Part 3 and Part 4: History of thromboembolic events within 3 months before the first dose of IP (limited to pulmonary embolism, deep vein thrombosis, or cerebral venous sinus thrombosis).

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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 Volrustomig Drug: T-DXd and Volrustomig T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: 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: Volrustomig Volrustomig: administered as an IV infusion Other Name: Other Name: MEDI5752
Experimental: Arm 3B: T-DXd, Volrustomig and Carboplatin Drug: T-DXd, Volrustomig and Carboplatin T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: 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: Volrustomig Volrustomig: administered as an IV infusion Other Name: Other Name: MEDI5752
Experimental: Arm 4A: T-DXd and Rilvegostomig T-DXd and Rilvegostomig Drug: T-DXd, Rilvegostomig T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Rilvegostomig, AZD2936	Drug: T-DXd T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Drug: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Other Name: AZD2936
Experimental: Arm 4B T-DXd and Rilvegostomig with Carboplatin Drug: T-DXd, Rilvegostomig and Carboplatin T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Rilvegostomig, AZD2936 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: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Other Name: AZD2936

Documents available

Lung Cancer Study Locator details (for US)
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Contact Backup

AstraZeneca Lung Cancer Study Locator Service

1-884-432-3892