New drug cocktail shows promise for tough lung cancer

NCT ID NCT04526691

Disease control Sponsor: Daiichi Sankyo Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This early-stage trial is testing a combination of two drugs—datopotamab deruxtecan (Dato-DXd) and pembrolizumab (Keytruda)—with or without standard chemotherapy in people with advanced non-small cell lung cancer. The goal is to see if the combination is safe and can shrink tumors. About 145 participants are enrolled, and researchers are monitoring side effects and how well the cancer responds.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (Keytruda) with or without platinum chemotherapy
What this could lead to: If successful, this combination could offer a new treatment option for advanced lung cancer that may shrink tumors or slow disease progression.
What could go wrong: This is an early Phase 1b trial with only 145 participants, so results are preliminary. Side effects from the drug combination could be significant, and the approach may not prove effective in larger studies.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

145 people

The number who actually took part.

Started

Sep 2020

Expected to finish

Dec 2026

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Histologically confirmed at diagnosis of NSCLC that: * Is advanced or metastatic. * Participants with non-squamous histology must have documented negative test results for actionable EGFR and ALK genomic alterations. Participants with squamous histology are required to undergo testing for EGFR and ALK genomic alterations if they are nonsmokers or under the age of 40 years. * Has either documented negative or unknown test results for actionable genomic alterations in ROS1, NTRK, BRAF, RET, MET, or other actionable oncogenic driver kinases. * Participants with tumors that harbor KRAS mutations are eligible for this study. * Participants with non-actionable genomic alterations in EGFR, ALK, ROS1, NTRK, BRAF, RET, MET, or other kinases are eligible for the study. * Documentation of radiological disease progression while on or after receiving the most recent treatment regimen, if any, for advanced or metastatic NSCLC. * Must meet the following prior therapy requirements for advanced or metastatic NSCLC: * Dose escalation (all cohorts): Has received ≤2 lines of prior anticancer therapy for locally advanced or metastatic NSCLC. * Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab): Has not received PD-1/PD-L1, PD-L2, CTLA-4 directed immunotherapy and may or may not have been treated with systemic chemotherapy for advanced or metastatic NSCLC. * Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab and 4 cycles of AUC 5 carboplatin or cisplatin 75 mg/m\^2): Has not been treated with systemic anticancer therapy for advanced or metastatic NSCLC. * Willing and able to undergo a mandatory tumor biopsy. * Archival tumor tissue from initial diagnosis, to the extent that archival tumor tissue is available, for measurement of TROP2 expression levels or other biomarkers. * Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 Day 1. * Is not a candidate for surgical resection or chemoradiation with curative intent. Exclusion Criteria: * Experienced grade 3 or higher immune-related adverse events (AEs) with prior treatment of anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). * Received a live vaccine within 30 days prior to the first dose of study treatment. * Active, known, or suspected autoimmune disease. * Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications, except for managing AEs. * Prior organ transplantation, including allogeneic tissue or solid organ transplantation. * Has 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. * History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses. * History of another primary malignancy (beyond NSCLC) except for: * Malignancy treated with curative intent and with no known active disease for ≥3 years. * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Adequately treated carcinoma in situ without evidence of disease. * Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression.

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Conditions

The condition(s) this trial relates to.

non-small cell lung carcinoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Advanced or metastatic NSCLC

Contacts and locations

Locations

(CIOCC-START) Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain
Azienda Ospedaliera San Gerardo

Monza, 20052, Italy
Chung Shan Medical University Hospital

Taichung, 40201, Taiwan
City of Hope

Duarte, California, 91010, United States
H. Vall Hebrón (Vall Hebron Institut de Oncologia - VHIO)

Barcelona, 08035, Spain
Hospital Puerta de Hierro

Majadahonda, 28222, Spain
Hospital Universitario 12 de Octubre

Madrid, 28041, Spain
Instituto Europeo Di Oncologica

Milan, 20141, Italy
Istituto Nazionale Tumori Fondazione G. Pascale di Napoli Struttura di Oncologia

Naples, 80131, Italy
Johns Hopkins Kimmel Cancer Center

Washington D.C., District of Columbia, 20016, United States
Johns Hopkins Kimmel Cancer Center at Bayview

Baltimore, Maryland, 21224, United States
Mayo Clinic

Scottsdale, Arizona, 85259, United States
Mayo Clinic

Jacksonville, Florida, 32224, United States
Mayo Clinic

Rochester, Minnesota, 55905, United States
NEXT Oncology

San Antonio, Texas, 78229, United States
National Cancer Center Hospital

Tokyo, 104-0045, Japan
National Cancer Center Hospital East

Chiba, 277-8577, Japan
National Cheng Kung University Hospital NCKUH

Tainan, 704, Taiwan
National Taiwan University Hospital NTUH

Taipei, 100, Taiwan
Quantum Santa Fe

Santa Fe, New Mexico, 87505, United States
START Madrid - Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain
Showa Medical University Hospital

Tokyo, 142-8555, Japan
Taichung Veterans General Hospital

Taichung, 40705, Taiwan
The Skip Viragh Outpatient Cancer Building

Baltimore, Maryland, 21287, United States

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