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

NCT04879849 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: TAK-676-1003U1111-1252-0338
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (5)

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity

  AE: any untoward medical occurrence in participants administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. TEAE: any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug is considered treatment emergent. Severity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Grade 1: Mild (asymptomatic/mild symptoms; clinical/diagnostic observations only; intervention not indicated); Grade 2: Moderate (minimal, local/noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living \[ADL\]); Grade 3: Severe (severe/medically significant but not immediately life-threatening hospitalization/prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4: Life-threatening consequences, urgent intervention indicated; Grade 5: Death related to AE.

  From first dose of study drug administration up to 32 months

• Number of Participants With Dose-limiting Toxicities (DLTs)

  A DLT was defined as any TEAE that occurred during Cycle 1 and was considered by investigator to be at least possibly related to TAK-676 in combination with pembrolizumab. TEAEs meeting DLT definitions occurring in later cycles were considered in the determination of recommended phase 2 dose (RP2D) of TAK-676. DLTs were assessed based on NCI CTCAE version 5.0.

  During Cycle 1 (cycle length= 21 days)

• Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs)

  TEAE: any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug is considered treatment emergent. An SAE is defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is a medically important event that satisfies any of the following: a) may require intervention to prevent items 1 through 5 above. b) may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization

  From first dose of study drug administration up to 32 months

• Number of Participants With One or More TEAEs Leading to Dose Modifications

  TEAE: Any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug is considered treatment emergent.

  From first dose of study drug administration up to 32 months

• Number of Participants With One or More TEAEs Leading to Treatment Discontinuation

  TEAE: Any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug is considered treatment emergent.

  From first dose of study drug administration up to 32 months

Secondary Outcomes (11)

• Overall Response Rate (ORR) Assessed by Investigator as Per RECIST v1.1

  Up to 32 months

• Duration of Response (DOR) For All Tumor Lesions Assessed by Investigator as Per RECIST v1.1

  Up to 32 months

• Time to Response (TTR) For All Tumor Lesions Assessed by Investigator as Per RECIST v1.1

  Up to 32 months

• Overall Response Rate Assessed by Investigator as Per Modified Intratumoral Immunotherapy RECIST (Modified itRECIST)

  Up to 32 months

• Overall Response Rate For Tumors Within the Radiation Field (ORRirradiated)

  Up to 32 months

Study Arms (1)

Combination Dose Escalation Phase: Radiation + Pembrolizumab + TAK-676

EXPERIMENTAL

Participants will receive image-guided radiation therapy between Day -8 and Day -2. Participants will then receive pembrolizumab 200 milligram (mg), infusion, intravenously (IV), once on Day 1 of Cycle 1 and then every 3 weeks in each 21-day treatment cycle, followed by TAK-676 infusion with escalating doses (0.2 mg and above), IV, once on Days 1, 8, 15 in each 21-day treatment cycle until disease progression, intolerance to pembrolizumab or TAK-676 or withdrawal of consent, whichever occurs first.

Drug: Pembrolizumab; Drug: TAK-676; Radiation: Image-guided radiation therapy

Interventions

Pembrolizumab DRUG

IV infusion.

Combination Dose Escalation Phase: Radiation + Pembrolizumab + TAK-676

TAK-676 DRUG

IV infusion.

Combination Dose Escalation Phase: Radiation + Pembrolizumab + TAK-676

Image-guided radiation therapy RADIATION

Radiation therapy.

Combination Dose Escalation Phase: Radiation + Pembrolizumab + TAK-676

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• 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.
• 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.
• Adequate bone marrow, renal and hepatic functions.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• Known history of uncontrolled autoimmune disorders, human immunodeficiency virus (HIV) infection, or other relevant congenital or acquired immunodeficiencies.
• Chronic, active hepatitis (example, participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus \[HCV\]-ribonucleic acid \[RNA\]).
• 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.
• Prior radiation to lesions chosen for biopsy or response assessment.
• 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).
• Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within 7 days of start of radiation therapy, with the following exceptions:
• Topical, intranasal, inhaled, ocular, intra-articular, and/or other nonsystemic corticosteroids.
• Physiological doses of replacement steroid therapy (example, for adrenal insufficiency).
• Receipt of live attenuated vaccine (example, tuberculosis Bacillus Calmette-guerin \[BCG\] vaccine, oral polio vaccine, measles, rotavirus, yellow fiver) within 28 days of C1D1 of study drug(s).
• Recipients of allogeneic or autologous stem cell transplantation or organ transplantation.
• Ongoing Grade ≥2 infection or participants with Grade ≥2 fever of malignant origin.

Sponsors & Collaborators

• Takeda: lead

Study Sites (5)

Cedars Sinai Medical Center

Duarte, California, 91010-3012, United States

Location

University of Chicago

Chicago, Illinois, 60637-1443, United States

Location

Laura And Isaac Perlmutter Cancer Center

New York, New York, 10016-4744, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213-2933, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-0021, United States

Location

Related Publications (2)

• Cooper BT, Iams WT, Page DB, Yuan Y, Gerber NK, Luke JJ, Gibbs JP, Gregory RC, Wong KK, Deng J, Perera SA, Ding K, Roberts ER, Berger A, Christensen CL, Tong EX, Maldonado Lopez AE, Appleman VA, Leonard EJ, Parent A, Huang YC, Bay C, Li C, Lineberry N, Raizer J, Olson DJ, Chmura SJ. Phase 1b Study of Dazostinag plus Pembrolizumab after Hypofractionated Radiotherapy in Patients with Select Advanced Solid Tumors. Cancer Res Commun. 2025 Dec 1;5(12):2249-2263. doi: 10.1158/2767-9764.CRC-25-0566.

  PMID: 41296842 DERIVED

• Carideo Cunniff E, Sato Y, Mai D, Appleman VA, Iwasaki S, Kolev V, Matsuda A, Shi J, Mochizuki M, Yoshikawa M, Huang J, Shen L, Haridas S, Shinde V, Gemski C, Roberts ER, Ghasemi O, Bazzazi H, Menon S, Traore T, Shi P, Thelen TD, Conlon J, Abu-Yousif AO, Arendt C, Shaw MH, Okaniwa M. TAK-676: A Novel Stimulator of Interferon Genes (STING) Agonist Promoting Durable IFN-dependent Antitumor Immunity in Preclinical Studies. Cancer Res Commun. 2022 Jun 23;2(6):489-502. doi: 10.1158/2767-9764.CRC-21-0161. eCollection 2022 Jun.

  PMID: 36923556 DERIVED

Related Links

• To obtain more information on the study, click here/on this link.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Radiotherapy, Image-Guided

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

Trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: May 10, 2021
• Study Start: September 9, 2021
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: September 4, 2025
• Results First Posted: September 4, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (5)