Loading clinical trials...

A Study of TAK-676 With Pembrolizumab After Radiation Therapy to Treat a Number of Cancers | Clinical Trials | Clareo Health

COMPLETEDPHASE1

A Study of TAK-676 With Pembrolizumab After Radiation Therapy to Treat a Number of Cancers

An Open-label, Phase 1, Dose-escalation Study to Evaluate the Safety and Preliminary Antitumor Activity of TAK-676 With Pembrolizumab Following Radiation Therapy in the Treatment of Non-small-cell Lung Cancer, Triple-negative Breast Cancer, or Squamous-cell Carcinoma of the Head and Neck That Has Progressed on Checkpoint Inhibitors

NCT04879849•Takeda

View on ClinicalTrials.gov

Summary

In this study, adults with non-small-cell lung cancer (NSCLC), triple-negative breast cancer (TNBC) and squamous-cell carcinoma of the head and neck (SCCHN) will be treated with TAK-676 and pembrolizumab following radiotherapy. The main aims of this study are to check if people are improving after treatment with TAK-676, getting side effects from these combined treatments, and how much TAK-676 people with these cancers can receive without getting unacceptable side effects from it. Participants will receive radiotherapy, then at least 40 hours later will receive pembrolizumab followed by TAK-676 slowly through a vein (infusion). Participants will receive an infusion of pembrolizumab at the same dose every 3 weeks. Different small groups of participants will receive lower to higher doses of TAK-676 on specific days of a 21-day cycle. This study will be happening at sites in North America.

Detailed Description

The drug being tested in this study is called TAK-676. This study will evaluate the safety, tolerability and preliminary antitumor activity of TAK-676 with pembrolizumab following radiation therapy in the treatment of advanced NSCLC, TNBC or SCCHN that has progressed on checkpoint inhibitors (CPIs) and will estimate the maximum tolerated dose (MTD) and determine the recommended phase 2 dose (RP2D) of this combination. The study will enroll approximately 65 participants. Participants will be assigned to dose escalating cohorts based on Bayesian Optimal Interval (BOIN) design. The starting dose of TAK-676 will be 0.2 mg and the subsequent dosing will be initiated based on the available safety and tolerability data from the previous cohort. This multi-center trial will be conducted in the United States. There will be many clinic visits. The number of visits will depend on the number of cycles of treatment. Participants will attend an end of treatment (EOT) visit 30 days after receiving their last dose of study drug or before the start of subsequent systemic anticancer therapy, whichever occurs first. They might continue to have check-ups every 12 weeks if they left the study for a reason apart from their cancer getting worse.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
•2. Participants must have at least 2 measurable lesions (i.e. ≥10 mm longest diameter for extranodal lesions, ≥15 mm short axis for lymph nodes), with at least one inside and at least one other outside of the radiation field. The tumor outside the radiation field must be accessible for biopsy, and the participant must consent to tumor biopsy at screening and during treatment.
•3. Participants must have pathologically confirmed (cytological diagnosis is adequate) advanced or metastatic NSCLC, TNBC, or SCCHN who have:
•* Received or been offered all established standard of care (SOC) treatment options for which they are eligible; and
•* Progressed on CPIs in a prior line of therapy.
•4. Adequate bone marrow, renal and hepatic functions.
•5. Left ventricular ejection fraction (LVEF) \>50%, as measured by echocardiogram or multiple-gated acquisition (MUGA) scan within 4 weeks before receiving the first dose of study drug.
•6. Clinically significant toxic effects of previous therapy have recovered to Grade 1 (per NCI CTCAE, V5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement therapy.

Exclusion Criteria

•1. History of any serious cardiac or cerebrovascular conditions in the last 6 months, including uncontrolled congestive heart disease, unstable angina, myocardial infarction, hypertension greater than or equal to (≥) 160/100 millimeter of mercury (mmHg) in spite of optimal therapy, cardiac arrhythmias, pericardial effusion, cardiomyopathy, or symptomatic stroke. Chronic, stable atrial fibrillation on stable anticoagulation therapy, including low molecular weight heparin, will be allowed.
•2. History of brain metastasis unless:
•* Clinically stable, (that is, treatment completed ≥4 weeks prior) following prior surgery, whole-brain radiation, or stereotactic radiosurgery, AND
•* Off corticosteroids.
•3. Known history of uncontrolled autoimmune disorders, human immunodeficiency virus (HIV) infection, or other relevant congenital or acquired immunodeficiencies.
•4. Chronic, active hepatitis (example, participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus \[HCV\]-ribonucleic acid \[RNA\]).
•5. Treatment with any investigational products and systemic anticancer drugs (including vascular endothelial growth factor (VEGF) inhibitors), within 14 days or 5 half-lives, whichever is shorter, before Cycle 1 Day 1 (C1D1) of study drugs.
•6. Prior radiation to lesions chosen for biopsy or response assessment.
•7. Prior radiation to lesions other than those chosen for radiation therapy or biopsy in the current protocol within 4 weeks of C1D1 of study drug(s).
•8. Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within 7 days of start of radiation therapy, with the following exceptions:
+13 more criteria

Locations (5)

Cedars Sinai Medical Center

Duarte, California, United States

University of Chicago

Chicago, Illinois, United States

Laura And Isaac Perlmutter Cancer Center

New York, New York, United States

Providence Portland Medical Center

Portland, Oregon, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Key Dates

Start Date

September 9, 2021

Primary Completion Date

April 30, 2024

Completion Date

April 30, 2024

Last Updated

September 4, 2025

Enrollment

ACTUAL participants

Conditions

Carcinoma, Non-Small-Cell LungTriple Negative Breast NeoplasmsSquamous Cell Carcinoma of Head and Neck

Interventions

Pembrolizumab

DRUG

TAK-676

DRUG

Image-guided radiation therapy

RADIATION

A Study of JNJ-90301900 in Combination With Chemoradiation Followed by Consolidation Immunotherapy for Non-Small Cell Lung Cancer (NSCLC)

NCT06667908

Carcinoma, Non-Small-Cell Lung

View study

RECRUITING

KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)

NCT04165798

Carcinoma, Non-Small-Cell Lung

View study

RECRUITING

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 4, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

A Study of TAK-676 With Pembrolizumab After Radiation Therapy to Treat a Number of Cancers

Inclusion Criteria

Exclusion Criteria

A Study of JNJ-90301900 in Combination With Chemoradiation Followed by Consolidation Immunotherapy for Non-Small Cell Lung Cancer (NSCLC)

KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)

A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer

A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

HN-BIO 02: A Phase II Randomized Study of the Effects of Delayed Elective Radiotherapy on Head and Neck MRI and Immune Response Biomarkers

A Study of LY4175408 in Participants With Advanced Cancer