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

Launched by DAIICHI SANKYO · Mar 21, 2025

Keywords

ClinConnect Summary

This clinical trial is studying the effects of a new treatment called trastuzumab deruxtecan (also known as T-DXd or Enhertu®) combined with pembrolizumab for patients with a specific type of lung cancer. The researchers want to see if this combination works better than the standard treatment, which includes pembrolizumab along with platinum-based chemotherapy. The trial is focused on adults who have not received previous treatment for their advanced or metastatic non-small cell lung cancer (NSCLC) and whose tumors overexpress a protein called HER2.

To be eligible for this trial, participants must be at least 18 years old and have a confirmed diagnosis of non-squamous advanced NSCLC that cannot be surgically removed. They should not have received any systemic cancer treatments for their advanced disease before joining the trial. Participants will need to provide a tumor tissue sample for testing, and those with certain heart or lung conditions will not be eligible. The trial is not yet open for recruitment, but it aims to offer new hope for patients facing this challenging type of cancer.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. 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 Screening ICF) prior to any PGx procedure, and the Pregnant Partner ICF, if applicable.
• • 2. 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.
• • 3. 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 existing test result of local test) 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 adenocarcinoma is the predominant histology. Mixed tumors will be classified based on the predominant cell type.
• • 4. 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 and should not have progressed on or within 6 months of the last dose date of adjuvant/neoadjuvant therapy.
• • 1. Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I.
• • 2. HER2-targeted antibody-based anticancer therapy.
• • 5. 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:
• • 1. 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 should have a cardiologic consultation during the Screening Period to rule out MI.
• • 2. Has a QTc prolongation to \>480 ms based on the average of the Screening triplicate 12- lead ECG.
• • 3. 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.
• • 4. Has lung-specific, intercurrent, clinically significant 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, etc.).
• • 5. Had a prior complete pneumonectomy.