A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Treatments: Drug: Trastuzumab Deruxtecan; Drug: Carboplatin; Drug: Pemetrexed; Drug: Pembrolizumab; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05048797

D967SC00001

2021-000634-33 (EudraCT Number)

2023-503674-20-00 (Registry Identifier)

Details and patient eligibility

About

DESTINY-Lung04 will investigate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd) versus Standard of Care (SoC) as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) with HER2 Exon 19 or 20 mutations

Full description

Eligible participants will be those diagnosed with unresectable, locally advanced or metastatic histologically documented non-squamous NSCLC with HER2 exons 19 or 20 mutations and who are treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease.

The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) as compared with Standard of Care treatment (Investigator's choice of cisplatin or carboplatin + pembrolizumab + pemetrexed). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse or simply to live longer, compared to patients receiving standard of care treatment. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

Enrollment: 454 patients

Sex: All

Ages: 18 to 123 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants at least 18 years of age
• Locally advanced and unresectable NSCLC, not amenable to curative therapy, or metastatic disease
• Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by tissue NGS or ctDNA
• Treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease
• Left ventricular ejection fraction (LVEF) ≥ 50%
• Measurable disease assessed by Investigator based on RECIST 1.1
• Protocol-defined adequate organ function including cardiac, renal, hepatic function
• ECOG 0-1
• Having tumour tissue available for central testing

Exclusion criteria

• Tumors with targetable alterations to EGFR (or other targetable mutations including but not limited to ALK, if routinely tested as a targetable alteration with approved available therapy)
• Any untreated brain metastases, including asymptomatic or clinically inactive brain metastases
• Active autoimmune or inflammatory disorders
• Medical history of myocardial infarction within 6 months prior to randomization
• History of non-infectious pneumonitis/ILD, current or suspected ILD
• Lung-specific intercurrent clinical significant severe illness
• Contraindication to platinum-based doublet chemotherapy or pembrolizumab

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

454 participants in 2 patient groups

Arm 1

Experimental group

Description:

Trastuzumab Deruxtecan (T-DXd)

Treatment:

Drug: Trastuzumab Deruxtecan

Arm 2

Active Comparator group

Description:

Standard of Care Treatment (platinum, pemetrexed and pembrolizumab)

Treatment:

Drug: Cisplatin

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Carboplatin