Recruiting NCT06899126

Study of Trastuzumab Deruxtecan, Pembrolizumab, and Platinum-based Chemotherapy in First-line HER2 Overexpressing Non-small Cell Lung Cancer

Phase III Interventional Non-small Cell Lung Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Trastuzumab Deruxtecan, pembrolizumab, Pemetrexed, Platinum Chemotherapy.
Who it may be relevant to: Registry conditions: Non-small Cell Lung Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Belgium, Brazil, Chile +18
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase 3, Multicenter, Randomized, Open-label Trial of Trastuzumab Deruxtecan in Combination With Pembrolizumab Versus Platinum-based Chemotherapy in Combination With Pembrolizumab, as First-line Therapy in Participants With Locally Advanced Unresectable or Metastatic HER2 Overexpressing and PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer (DESTINY-Lung06)

Overview

This clinical trial is designed to assess the efficacy and safety of trastuzumab deruxtecan (T-DXd; Enhertu®) in combination with pembrolizumab versus platinum-based chemotherapy in combination with pembrolizumab in participants with no prior therapy for locally advanced unresectable or metastatic non-squamous NSCLC, whose tumors have HER2-overexpressing and PD-L1 TPS \<50% without known AGA that have locally available therapies targeting their AGAs in first-line advanced/metastatic setting.

Interventions

Drug Trastuzumab Deruxtecan
T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)
Drug pembrolizumab
pembrolizumab will be administered at a dose of 200 mg IV Q3W
Drug Pemetrexed
Pemetrexed will be administered at a dose of 500 mg/m\^2 IV Q3W
Drug Platinum Chemotherapy
One of the following two will be administered in Arm B: Cisplatin at a dose of 75 mg/m\^2 IV or carboplatin AUC at a dose of 5 mg/mL/min IV Q3W

Primary outcome measures

Progression Free Survival by Blinded Independent Central Review [Time frame: From date of randomization to the date of radiographic disease progression or death due to any cause, up to approximately 54 months]

Secondary outcome measures (1)

Overall Survival [Time frame: From date of randomization to the date of death due to any cause, up to approximately 85 months]

Eligibility criteria

Inclusion criteria

Sign and date the Tissue Screening ICF, prior to any Tissue Screening procedure. Sign and date the Main ICF, prior to the start of any trial-specific qualification procedures.

Sign and date the Optional PGx ICF (included in the Main ICF) prior to any PGx procedure, and the Pregnant Partner ICF, if applicable.

Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is >18 years old.
Histologically documented non-squamous locally advanced unresectable or metastatic

NSCLC and meets all of the following criteria:

Has Stage IV NSCLC disease or Stage IIIB or IIIC disease but is not a candidate for surgical resection or definitive chemoradiation at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition). Has no known AGAs (based on the local test results obtained using validated or approved tests as required per local regulation) that have locally available therapies targeting their AGAs in the first-line advanced/metastatic setting.

Has no known HER2 mutation based on existing test results (if approved or validated local test is available). Note: Participants with mixed histology are eligible if non-squamous NSCLC is the predominant histology. Mixed tumors will be classified based on the predominant cell type.

Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Participants who received adjuvant or neoadjuvant therapy other than those listed below, including ICI (ie, anti-PD-1/PD-L1) or a platinum-based regimen, are eligible if the last dose of adjuvant/neoadjuvant therapy was given at least 6 months before the date of the first trial dose if their disease has progressed at least 6 months after the last dose date of adjuvant/neoadjuvant therapy.

Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I.
HER2-targeted antibody-based anticancer therapy.
Has adequate tumor tissue sample (not previously irradiated) available for assessment of HER2 and PD-L1 expression by central or Sponsor-specified laboratory. A new biopsy is required if the participant's most recent archival tumor tissue sample cannot be supplied.

Details pertaining to tumor tissue submission can be found in the Trial Laboratory Manual.

Exclusion criteria

Has a medical history of MI within 6 months before randomization/enrollment or symptomatic CHF (NYHA Class II to Class IV). Participants with troponin levels above the ULN at Screening (as defined by the manufacturer) and without any MI-related symptoms must be ruled out for MI. It is highly recommended that the investigator refer such participants for a cardiologic consultation during the Screening Period.
Has a QTc prolongation to >480 ms based on the average of the Screening triplicate 12- lead ECG.
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.
Has clinically severe pulmonary compromise resulting from intercurrent, pulmonary illnesses including, but not limited to:

Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the trial randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion).
Any auto immune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis).

Severe conditions are those defined as impacting daily activities and/or requiring use of supplemental oxygen.

Had a prior complete pneumonectomy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment

Study locations

China · 31 centers

Beijing Cancer Hospital — Beijing
China-Japan Friendship hospital — Beijing
Jilin Cancer Hospital — Changchun
The First Hospital of Jilin University — Changchun
Hunan Cancer Hospital — Changsha
Sichuan Cancer Hospital — Chengdu
West China Hospital, Sichuan University — Chengdu
Chongqing University Cancer Hospital — Chongqing
… and 23 more centers

United States · 26 centers

Alaska Oncology & Hematology, LLC — Anchorage
Orange Coast Memorial Medical Center Fountain Valley — Fountain Valley
California Research Institute — Los Angeles
Los Angeles Cancer Network (LACN) — Los Angeles
Providence Medical Foundation — Santa Rosa
Bay Pines VA Healthcare System — Bay Pines
Lynn Cancer Institute Center — Boca Raton
Holy Cross Hospital — Fort Lauderdale
… and 18 more centers

Japan · 22 centers