Carcinoma, Non-Small-Cell LungPhase 1NCT04879849
A Study of TAK-676 With Pembrolizumab After Radiation Therapy to Treat a Number of Cancers
A Phase 1 study testing Pembrolizumab, TAK-676 and Image-guided radiation therapy in people with Carcinoma, Non-Small-Cell Lung and Triple Negative Breast Neoplasms, run by Takeda at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Squamous Cell Carcinoma of Head and Neck
- What is being tested?
- Pembrolizumab, TAK-676 and Image-guided radiation therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 5 sitesUnited States
- Study dates
- 9 Sep 2021to 30 Apr 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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]).
Show all 23Show fewer
- 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.
- Fridericia's corrected QT interval (QTcF) >450 milliseconds (msec) (males) or >475 msec (females) on a 12-lead electrocardiogram (ECG) during the screening period.
- Grade ≥2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during C1D1 pre-dose assessment.
- Oxygen saturation less than (<) 92% on room air at screening or during C1D1 predose assessment.
- Use of medications that are known clinical organic anion transporting polypeptide 1B1 (OATP1B1) and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of study drugs.
- Current smoker.
- Vaping within 90 days of C1D1 of study drugs.
- Current diagnosis of pneumonitis, interstitial lung disease, severe chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, other restrictive lung diseases, acute pulmonary embolism, or Grade ≥2 pleural effusion or ascites not controlled by tap or requiring indwelling catheters.
- Treated with other stimulator of interferon genes (STING) agonists/antagonist and toll-like receptors agonists within the past 6 months.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Chicago
Chicago, Illinois, 60637-1443
Cedars Sinai Medical Center
Duarte, California, 91010-3012
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-0021
Laura And Isaac Perlmutter Cancer Center
New York, New York, 10016-4744
Providence Portland Medical Center
Portland, Oregon, 97213-2933
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Squamous Cell Carcinoma of Head and Neck
- Being tested
- Pembrolizumab, TAK-676, Image-guided radiation therapy
- Keywords
- Drug Therapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
IV infusion.
TAK-676Drug
IV infusion.
Image-guided radiation therapyRadiation
Radiation therapy.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pembrolizumab; Drug: TAK-676; Radiation: Image-guided radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
ORR was defined as the percentage of participants who achieved confirmed complete response (cCR) or confirmed partial response (cPR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version1.1 (RECIST, V1.1). Complete Response (CR) for Target Lesions was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeter (mm) and for Nontarget Lesions was defined as disappearance of all nontarget lesions and normalization of tumor marker level and all lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR) was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. The second assessment confirming a CR or PR must have taken place at least 4 weeks after the response of interest. Percentages were rounded off to nearest single decimal place.
Measured: Up to 32 months
Duration of Response (DOR) For All Tumor Lesions Assessed by Investigator as Per RECIST v1.1
DOR:time from 1st documentation of cPR/better to 1st documentation of progressive disease(PD) for responders(cPR or better).PR:at least 30% decrease in sum of LD of target lesions,with reference of baseline sum LD.2nd assessment confirming PR must have taken place at least 4 weeks after response of interest.PD of Target Lesions:at least 20% increase in sum of LD of target lesions,with reference of smallest sum LD recorded since treatment started/appearance of 1/more new lesions.PD of Nontarget Lesions:unequivocal progression of existing non-target lesions.Responders without documentation of PD were censored at last response assessment that was stable disease(SD) or better.SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,with reference of smallest sum LD since treatment started.Evaluation was determined by investigator according to RECIST, V1.1.2nd assessment confirming CR/PR must have taken place at least 4 weeks after response of interest.
Measured: Up to 32 months
Time to Response (TTR) For All Tumor Lesions Assessed by Investigator as Per RECIST v1.1
TTR was defined as the time from the date of first dose administration to the date of first documented cPR or better as determined by the investigator according to RECIST, V1.1. PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. The second assessment confirming a CR or PR must have taken place at least 4 weeks after the response of interest.
Measured: Up to 32 months
Overall Response Rate Assessed by Investigator as Per Modified Intratumoral Immunotherapy RECIST (Modified itRECIST)
ORR was defined as the percentage of participants who achieve cCR or cPR as determined by the investigator according to Modified itRECIST. CR for Target Lesions was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm and for Nontarget Lesions was defined as disappearance of all nontarget lesions and normalization of tumor marker level and all lymph nodes must be non-pathological in size (<10 mm short axis). PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. The second assessment confirming a CR or PR must have taken place at least 4 weeks after the response of interest. Percentages were rounded off to the nearest single decimal place.
Measured: Up to 32 months
Overall Response Rate For Tumors Within the Radiation Field (ORRirradiated)
ORRirradiated was defined as the percentage of participants who achieve cCRirradiated or cPRirradiated in the tumor lesions lying within the radiation field as determined by the investigator according to modified itRECIST. CR for Target Lesions was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm and for Nontarget Lesions was defined as disappearance of all nontarget lesions and normalization of tumor marker level and all lymph nodes must be non-pathological in size (<10 mm short axis). PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. The second assessment confirming a CR or PR must have taken place at least 4 weeks after the response of interest. Percentages were rounded off to the nearest single decimal place.
Measured: Up to 32 months
Overall Response Rate For Tumors Outside the Radiation Field (ORRnonirradiated)
ORRnonirradiated was defined as the percentage of participants who achieve cCRnonirradiated or cPRnonirradiated in the tumor lesions lying outside of the radiation field as determined by the investigator according to modified itRECIST. CR for Target Lesions was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm and for Nontarget Lesions was defined as disappearance of all nontarget lesions and normalization of tumor marker level and all lymph nodes must be non-pathological in size (<10 mm short axis). PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. The second assessment confirming a CR or PR must have taken place at least 4 weeks after the response of interest. Percentages were rounded off to the nearest single decimal place.
Measured: Up to 32 months
Duration of Response (DOR) For Tumors Within the Radiation Field (DORirradiated)
DORirradiated for tumor lesions lying within radiation field: as time from the date of first documentation of a cPRirradiated or better to the date of first documentation of irradiated PD in those lesions for irradiated responders (cPRirradiated or better). PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Irradiated responders without documentation of irradiated PD were censored at the date of last response assessment that is irradiated SD or better. PD of Target Lesions: at least a 20% increase in sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment started or appearance of 1 or more new lesions. PD of Nontarget Lesions: unequivocal progression of existing non-target lesions. Evaluation was determined by the investigator according to modified itRECIST. The second assessment confirming a CR or PR must have taken place at least 4 weeks after the response of interest.
Measured: Up to 32 months
Duration of Response (DOR) For Tumors Outside the Radiation Field (DORnonirradiated)
DORnonirradiated for tumor lesions lying outside of the radiation field was defined as time from the date of first documentation of a cPRnonirradiated or better to the date of first documentation of nonirradiated PD in those lesions for nonirradiated responders (cPRnonirradiated or better). PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Nonirradiated responders without documentation of nonirradiated PD were censored at the date of last response assessment that is nonirradiated SD or better. Evaluation was determined by the investigator according to modified itRECIST. The second assessment confirming a CR or PR must have taken place at least 4 weeks after the response of interest.
Measured: Up to 32 months
Time to Response (TTR) For Tumors Within the Radiation Field (TTRirradiated)
TTRirradiated in the tumor lesions lying within the radiation field was defined as the time from the date of first dose administration to the date of first documented cPRirradiated or better as determined by the investigator according to modified itRECIST. PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. The second assessment confirming a CR or PR must have taken place at least 4 weeks after the response of interest.
Measured: Up to 32 months
Time to Response (TTR) For Tumors Outside the Radiation Field (TTR Nonirradiated)
TTR nonirradiated in the tumor lesions lying outside of the radiation field was defined as the time from the date of first dose administration to the date of first documented cPRnonirradiated or better during the study in response-evaluable population as determined by the investigator according to modified itRECIST. PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. The second assessment confirming a CR or PR must have taken place at least 4 weeks after the response of interest.
Measured: Up to 32 months
Number of Participants With Increase in T-Cell Infiltration in Tumor Evaluated by Immunohistochemistry
The T-cell infiltration levels were calculated as a change from pre-treatment to post-treatment levels. Number of participants who expressed increase in T-cell infiltration levels between the pre-treatment and post-treatment tumor biopsies are reported.
Measured: Up to approximately 32 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2021
- Study start9 Sep 2021
- Primary completion30 Apr 2024
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04879849
- Sponsor's protocol ID
- TAK-676-1003
- Other IDs
- U1111-1252-0338
- Status last verified
- Sep 2025
- First submitted
- 7 May 2021
- Last updated
- 4 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Saravanakumar A, Deng R, Dong L, Haridas S, Xia CQ, Appleman VA, Abu-Yousif AO, Piatkov K, Wang H. Population-Based Modeling to Predict Human PK/PD of TAK-500, an Anti-CCR2 Antibody-Drug Conjugate for First-in-Human Study in Cancer Patients. Clin Transl Sci. 2026 Apr;19(4):e70522. doi: 10.1111/cts.70522.
PubMed 41888610Cooper 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.
PubMed 41296842Carideo 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.
PubMed 36923556
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04879849
- Acronym / sponsor ID
- TAK-676-1003
- Conditions
- Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Squamous Cell Carcinoma of Head and Neck
- Keywords
- Drug Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 9 Sep 2021 (actual)
- Primary completion
- 30 Apr 2024 (actual)
- Study completion
- 30 Apr 2024 (actual)
- First posted
- 10 May 2021 (actual)
- Results
- Posted 4 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Dose Escalation Phase: Radiation + Pembrolizumab + TAK-676 | Experimental | Drug: Pembrolizumab, Drug: TAK-676, Radiation: Image-guided radiation therapyParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- 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.
Key exclusion criteria (23 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabIV infusion. | Drug | Combination Dose Escalation Phase: Radiation + Pembrolizumab + TAK-676 |
| TAK-676IV infusion. | Drug | Combination Dose Escalation Phase: Radiation + Pembrolizumab + TAK-676 |
| Image-guided radiation therapyRadiation therapy. | Radiation | Combination Dose Escalation Phase: Radiation + Pembrolizumab + TAK-676 |
Primary outcome
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity
Time frame: From first dose of study drug administration up to 32 months
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.
Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: During Cycle 1 (cycle length= 21 days)
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.
Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of study drug administration up to 32 months
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
Number of Participants With One or More TEAEs Leading to Dose Modifications
Time frame: From first dose of study drug administration up to 32 months
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.
Number of Participants With One or More TEAEs Leading to Treatment Discontinuation
Time frame: From first dose of study drug administration up to 32 months
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.
11 secondary outcomes
Overall Response Rate (ORR) Assessed by Investigator as Per RECIST v1.1
Time frame: Up to 32 months
Duration of Response (DOR) For All Tumor Lesions Assessed by Investigator as Per RECIST v1.1
Time frame: Up to 32 months
Time to Response (TTR) For All Tumor Lesions Assessed by Investigator as Per RECIST v1.1
Time frame: Up to 32 months
Overall Response Rate Assessed by Investigator as Per Modified Intratumoral Immunotherapy RECIST (Modified itRECIST)
Time frame: Up to 32 months
Overall Response Rate For Tumors Within the Radiation Field (ORRirradiated)
Time frame: Up to 32 months
Overall Response Rate For Tumors Outside the Radiation Field (ORRnonirradiated)
Time frame: Up to 32 months
Duration of Response (DOR) For Tumors Within the Radiation Field (DORirradiated)
Time frame: Up to 32 months
Duration of Response (DOR) For Tumors Outside the Radiation Field (DORnonirradiated)
Time frame: Up to 32 months
Time to Response (TTR) For Tumors Within the Radiation Field (TTRirradiated)
Time frame: Up to 32 months
Time to Response (TTR) For Tumors Outside the Radiation Field (TTR Nonirradiated)
Time frame: Up to 32 months
Number of Participants With Increase in T-Cell Infiltration in Tumor Evaluated by Immunohistochemistry
Time frame: Up to approximately 32 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41888610Saravanakumar A, Deng R, Dong L, Haridas S, Xia CQ, Appleman VA, Abu-Yousif AO, Piatkov K, Wang H. Population-Based Modeling to Predict Human PK/PD of TAK-500, an Anti-CCR2 Antibody-Drug Conjugate for First-in-Human Study in Cancer Patients. Clin Transl Sci. 2026 Apr;19(4):e70522. doi: 10.1111/cts.70522.
- Derived from this study: PubMed 41296842Cooper 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.
- Derived from this study: PubMed 36923556Carideo 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.
- To obtain more information on the study, click here/on this link.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab, TAK-676 and Image-guided radiation therapy in people with Carcinoma, Non-Small-Cell Lung and Triple Negative Breast Neoplasms, run by Takeda at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity (time frame: From first dose of study drug administration up to 32 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04879849, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2025.