New drug cocktail shows promise for Hard-to-Treat cancers

NCT ID NCT04042701

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

First seen Jun 26, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This early-stage trial is testing a combination of two drugs—trastuzumab deruxtecan (a targeted chemotherapy) and pembrolizumab (an immunotherapy)—in about 115 adults with advanced breast or non-small cell lung cancer that has a specific marker called HER2. The study has two parts: first, finding the safest dose of the combo, and then checking how well it shrinks tumors. Participants must have tried other treatments before and be willing to provide tumor samples.

What this could mean

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

Active substance: trastuzumab deruxtecan (a targeted chemotherapy) and pembrolizumab (an immunotherapy)
What this could lead to: If this combination works, it could offer a new treatment option for people with advanced HER2-positive breast or lung cancer that has stopped responding to other therapies.
What could go wrong: This is an early phase 1 trial with only 115 participants, so it is primarily testing safety and dosing. The combination may cause significant side effects, and it is too soon to know if it will be effective or widely available.

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

About 115 people

The number the study aims to enrol. It can still change while the study runs.

Started

Feb 2020

Expected to finish

Mar 2027

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: * Written informed consent * Adults ≥18 years * Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 * Pathologically documented HER2-expressing locally advanced/metastatic breast cancer, and HER2-expressing or HER2-mutant locally advanced/metastatic NSCLC * Willing to provide a tumor biopsy during screening and during treatment * Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator * Adequate cardiac function, as defined by left ventricular ejection fraction (LVEF) ≥50% within 28 days before enrollment. * Adequate organ function * Adequate treatment washout period before enrollment Inclusion Criteria Specific to Part 1 * Participants in Part 1 should meet the additional inclusion criteria listed for 1 of the 4 cohorts in Part 2. Inclusion Criteria Specific to Part 2 Inclusion Criteria for Cohort 1 * Pathologically documented, locally advanced/metastatic breast cancer that has centrally determined HER2-positive expression as per American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) Guidelines * Received prior trastuzumab emtansine (T-DM1) therapy with documented progression Inclusion Criteria for Cohort 2 * Pathologically documented, locally advanced/metastatic breast cancer that has centrally determined HER2-low expression (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization \[ISH-\]) * Participants must have exhausted treatments that can confer any clinically meaningful benefit (eg, other therapies such as hormonal therapy for participants who are hormone receptor positive) Inclusion Criteria for Cohort 3 * Pathologically documented, locally advanced/metastatic NSCLC that has centrally or locally determined HER2-expression (IHC 1+, 2+, or 3+) * Participants who have known epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK), BRAF V600E mutation, or ROS1 fusion should have disease progression after treatment with at least one genomically-targeted therapy for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment Inclusion Criteria for Cohort 4 * Pathologically documented, locally advanced/metastatic HER2-mutant NSCLC * Participants who have known EGFR mutation, ALK, BRAF V600E mutation, or ROS1 fusion should have disease progression after treatment with at least one genomically-targeted therapy for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment Exclusion Criteria: * Prior treatment with pembrolizumab or DS-8201a * Medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before enrollment to rule out MI * Corrected QT interval (QTc) prolongation to \>470 ms (females) or \>450 ms (males) * 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 * Spinal cord compression or clinically active central nervous system metastases * Active, known or suspected autoimmune disease * Condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment * Prior therapy with an anti-PD-1 or anti-PD-L1 agent * Prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE) * Prior anti-HER2 therapy is not allowed for participants with HER2 low-expressing breast cancer or participants with NSCLC (Cohorts 2, 3, or 4). Prior treatment with pan-HER tyrosine kinase inhibitor is allowed. * Prior systemic anticancer therapy, including investigational agents within 2 to 6 weeks prior to treatment * Unresolved toxicities from previous anticancer therapy * Live vaccine within 30 days prior to the first dose of study drug * Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment * Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral breast cancer * History of severe hypersensitivity reactions to other monoclonal antibodies and/or any of the study drug components * Active infection requiring systemic therapy * Known history of human immunodeficiency virus (HIV) infection * Active hepatitis B or C virus infection * History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, or any other reason the participant is found not appropriate to participate in the opinion of the treating Investigator * Known psychiatric or substance abuse disorders * Prior organ transplantation, including allogeneic stem cell transplantation * Pregnant, breastfeeding, or planning to become pregnant * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses * Uncontrolled infection requiring IV antibiotics, anti-virals, or anti-fungals

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Conditions

The condition(s) this trial relates to.

breast cancer breast neoplasm HER2 positive breast carcinoma non-small cell lung carcinoma

As listed by the trial registrant

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

Breast cancer Non small cell lung carcinoma

Contacts and locations

Locations

CHU de Poitiers

Poitiers, 86000, France
CHUTimone

Marseille, 13385, France
Cancer Specialists of North Florida (Cbo)

Jacksonville, Florida, 32256, United States
Center for Cancer & Blood Disorders

Bethesda, Maryland, 20817, United States
Centre Hospitalier Intercommunal de Créteil

Créteil, 94000, France
Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States
Hope Cancer Center of East Texas

Tyler, Texas, 75701, United States
Hopital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, 35016, Spain
Hospital General Univ. Gregorio Marañon

Madrid, 28009, Spain
Hospital Teresa Herrera (C.H.U.A.C)

A Coruña, 15006, Spain
Hospital Universitario 12 de Octubre

Madrid, 28041, Spain
Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain
Hospital Universitario Virgen Macarena

Seville, 41009, Spain
Hospital de la Santa Creu i de Sant Pau

Barcelona, 08025, Spain
Inst. Oncologico Baselga Hospital Quiron

Barcelona, 08023, Spain
Institut Bergonie

Bordeaux, 33000, France
Institut Gustave Roussy

Villejuif, 94805, France
Institut PAOLI-CALMETTES

Marsielle, 13273, France
MD Anderson Cancer Center

Madrid, 28033, Spain
Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States
Moffit Cancer Center

Tampa, Florida, 33612, United States
Moffitt Cancer Center

Tampa, Florida, 32256, United States
Royal Marsden Hosptial

Sutton, SM2 5PT, United Kingdom
Sarah Cannon Research Institute (SCRI)

London, W1G 6AD, United Kingdom
Siteman Cancer Center-Washington University

St Louis, Missouri, 63110, United States
The Christie NHS Fond. Trust

Manchester, M20 4BX, United Kingdom
The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom
Univ. du Cancer de Toulouse

Toulouse, 31100, France
Univ. of Cali. San Francisco Medical Center

San Francisco, California, 94143, United States
Yale Cancer Center

New Haven, Connecticut, 06520, United States

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