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

NCT ID NCT04420884

Disease control Sponsor: Takeda Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study tested a new drug called TAK-676, alone and with pembrolizumab, in 248 adults with advanced solid tumors that had no standard treatment options. The main goal was to check safety and find the highest dose that causes few side effects. The study also looked at how well the drugs shrank tumors in certain cancers like head and neck cancer and colorectal cancer.

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Study facts

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

Phase

Phase 1/2

Runs two stages together: safety and dose first, then whether the treatment works.

Participants

248 people

The number who actually took part.

Started

Jul 2020

Finished

Mar 2026

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: 1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 2. Dazostinag SA (dose escalation Part 1A): o With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to these therapies. 3. Dazostinag in combination with pembrolizumab (dose escalation Parts 1B and Japan safety lead-in): * With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to them, including: * Tumors that have relapsed or are refractory to anti-programmed cell death ligand protein 1 (anti PD-(L)-1) therapy. * Tumors that are naive to anti-PD-(L)-1 therapy. 4. For expansion phase only: * SCCHN (Part 2): * Participants with histologically confirmed (cytological diagnosis is acceptable) metastatic or recurrent, unresectable SCCHN that is considered incurable by local therapies. Participants should not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months before signing consent if given as part of multimodal treatment of locally advanced disease is allowed. * Anatomic subsites to be included are oral cavity, oropharynx, hypopharynx, larynx, nasal cavity, and paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal). The exception to this is nasopharyngeal cancer and salivary gland tumors, which will not be included. * Participants with oropharyngeal cancer or tumors arising in the paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal) must agree to provide archival tissue for human papilloma virus (HPV) testing or if known, HPV testing results (using CINtec® p16 Histology assay is preferred but not required) and a 70% cutoff point must be provided. Alternatively, archival tissue or a fresh excisional or core needle biopsy (≥ 2 cores) is required for the determination of HPV status. If HPV status was previously tested using this method (CINtec® p16 Histology assay is preferred but not required), no additional testing is required. Archival tissue can be obtained up to 90 days prior to screening. Samples that are older than 90 days at screening may be used after consultation with the sponsor. * For Part 2A, tumors must have a PD-L1 CPS ≥ 1. Participants must agree to provide fresh tumor biopsy for analysis from a core or excisional biopsy (fine needle aspirate is not sufficient) at screening for PD-L1 CPS assessment by a central laboratory. This specimen may be the diagnostic sample for participants with a new diagnosis of metastatic SCCHN. Participants for whom newly obtained samples cannot be obtained (eg, inaccessible or participant safety concern) may submit an archived specimen only upon agreement from the Sponsor. Archival tissue can be obtained up to 90 days prior to screening provided there was no other treatment from the time of biopsy until the start of study treatment. For Part 2B, any CPS is eligible but fresh or archival tissue is required for confirmation of CPS status. Collection of the tissue samples for PD-L1 assessments for Part 2B can be discontinued by the sponsor if sufficient data has been collected or dazostinag activity does not justify further collection. * For Part 2B, participants must be eligible to receive treatment with either cisplatin or carboplatin in combination with 5-fluorouracil (5-FU) per the treating physician. 5. CRC (Part 3): * Third-line or later MSI-H/dMMR CRC (Part 3A): Participants with histologically confirmed (cytological diagnosis is acceptable) recurrent locally advanced or metastatic MSI-H/dMMR CRC whose disease has progressed on or following therapy with 1) an anti-PD-1 or PD-L1 antibody (i.e., pembrolizumab) and 2) at least one line of combination chemotherapy including a fluoropyrimidine and irinotecan OR oxaliplatin with or without an anti-epidermal growth factor receptor (EGFR) or anti-vascular endothelial growth factor (VEGFR) monoclonal antibody (i.e., cetuximab or bevacizumab). MSI-H/dMMR CRC participants must have received at least 6 weeks of prior treatment with an anti-PD-(L)-1 antibody. Only one line of anti-PD-(L)-1 is permitted. * Third-line MSS/pMMR CRC (Part 3B): Participants with histologically confirmed (cytological diagnosis is acceptable) recurrent locally advanced or metastatic MSS/pMMR CRC whose disease has progressed on or following therapy with 2 different lines of combination chemotherapy, including therapy with a fluoropyrimidine and irinotecan AND therapy with a fluoropyrimidine and oxaliplatin. Both lines of therapy may be given with or without an anti-EGFR or anti-VEGFR monoclonal antibody (i.e., cetuximab or bevacizumab). Participants with MSS/pMMR CRC must have progressed on or after combination chemotherapy regimens containing BOTH irinotecan AND oxaliplatin. * Participants with MSI-H/dMMR or MSS/pMMR CRC must have documented MSI/MMR status assessed by a Clinical Laboratory Improvements Amendment-certified (United States \[US\] sites or an accredited (outside of the US) local laboratory using immunohistochemistry (IHC) and/or polymerase chain reaction (PCR) or next generation sequencing (NGS) assay. * Adequate tumor tissue available for central laboratory confirmation of MSI/MMR status. Note: confirmation of central test positivity is not required before treatment. * Participants with MSI-H/dMMR or MSS/pMMR CRC must have been treated with 2 prior lines of therapy in the recurrent locally advanced or metastatic setting. 6. Adequate bone marrow, renal, hepatic and cardiac functions. 7. 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. 8. Clinically significant toxic effects of previous therapy have recovered to Grade 1 (per NCI CTCAE Version 5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement therapy. 9. In dose escalation Part 1, (not applicable for the Japan safety lead-in) once peripheral evidence of dazostinag pharmacodynamic stimulation of the innate and/or adaptive immune system is observed in the blood and/or an imaging response/partial response (CR/PR) is observed in at least 1 participant, subsequent participants must: * Have at least 1 lesion amenable for biopsy. * Agree to have 2 tumor biopsies: 1 during the screening period and 1 while on dazostinag treatment. 10. Must have at least 1 RECIST version 1.1-evaluable (measurable) lesion. For the dose escalation phase (Part 1) only, nonmeasurable only disease is acceptable. 11. Pharmacokinetic (PK)/pharmacodynamic blood must be drawn on a peripherally-inserted catheter. Dazostinag is preferentially administered through a central line, but peripheral infusion is acceptable. If a peripheral line is used for dazostinag and/or pembrolizumab infusion, it must be separate than the one used for PK/pharmacodynamic collection. Exclusion Criteria: 1. Corrected QT interval by Fredericia (QTcF) greater than (\>) 450 milliseconds (men) or \> 475 milliseconds (women) on a 12-lead electrocardiogram (ECG) during the screening period. 2. Grade greater than or equal to (≥) 2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during Cycle 0 Day 1 (C0D1) \[for Japan safety lead-in only\] and Cycle 1 Day 1 (C1D1) predose assessment. 3. Oxygen saturation less than (\<) 92 percent (%) on room air at screening or during C0D1 (for Japan safety lead-in only) and C1D1 predose assessment. 4. Treated with other STING agonists/antagonist and toll-like receptors agonists within the past 6 months. 5. Current history of pneumonitis, interstitial lung disease, severe chronic obstructive pulmonary disease, 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. 6. History of brain and leptomeningeal metastasis unless: * Brain metastases are clinically and radiologically stable or improved (that is, ≥ 4 weeks) following surgery, whole-brain radiation, or stereotactic radiosurgery, AND * Off corticosteroids. 7. Ongoing Grade ≥ 2 infection or participants with Grade ≥ 2 fever of malignant origin. 8. Chronic, active hepatitis (example: participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus \[HCV\]- ribonucleic acid \[RNA\]). 9. For participants in the dose escalation SA Part 1A only: refusal of standard therapeutic options. 10. For participants receiving pembrolizumab only: contraindication and/or intolerance to the administration of pembrolizumab. 11. For participants receiving chemotherapy in Part 2B: contraindication and/or intolerance to the administration of both platinum agents (cisplatin and carboplatin) and/or 5-FU. 12. Participant has had any other prior or concurrent malignancy within 2 years prior to enrollment with the following exceptions: adequately treated localized basal cell or squamous cell carcinoma, or curatively treated in situ carcinoma of the cervix or breast. Other exceptions may be considered upon sponsor consultation. 13. Concurrent chemotherapy (except for Part 2B), immunotherapy (except for pembrolizumab in Part 1B, Part 2, and Part 3), biologic, or hormonal therapy (except for adjuvant endocrine therapy for a history of breast cancer). Concurrent use of hormones for noncancer-related conditions is acceptable (except for corticosteroid hormones) unless allowed per exclusion criterion 16. 14. Radiation therapy within 14 days (42 days for radiation to the lungs) and/or systemic treatment with radionuclides within 42 days before C1D1 of study drug(s). Participants with clinically relevant ongoing pulmonary complications from prior radiation therapy are not eligible. 15. Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within 7 days of C1D1 of study drug(s), with the following exceptions: * Topical, intranasal, inhaled, ocular, intra-articular, and/or other non-systemic corticosteroids. * Premedications required for computed tomography (CT) or magnetic resonance imaging (MRI) scans. * Physiological doses of replacement steroid therapy (example: for adrenal insufficiency). * For participants enrolled in Part 2B, chemotherapy premedication with steroids can be administered according to local standards of care practice. 16. Use of medications that are known clinical organic anion-transporting polypeptide B1 (OATP1B1) and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of study drug(s). 17. Receipt of live attenuated vaccine (eg, tuberculosis Bacillus Calmette-Guerin vaccine, oral polio vaccine, measles, rotavirus, yellow fever) within 28 days of C1D1 of study drug(s). 18. Recipients of allogeneic or autologous stem cell transplantation or organ transplantation. For Part 2 SCCHN only: 19. Has progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced SCCHN. 20. Has a life expectancy of less than 3 months and/or has rapidly progressive disease (eg, tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator. 21. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent. 22. Participants with known dihydropyrimidine dehydrogenase (DPD) deficiency or thymidine phosphorylase gene (TYMP) mutations (Part 2B only).

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Conditions

The condition(s) this trial relates to.

colorectal cancer head and neck squamous cell carcinoma metastatic malignant neoplasm neoplasm

As listed by the trial registrant

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

Solid neoplasms

Contacts and locations

Locations

Barbara Ann Karmanos Cancer Institute - Lawrence and Idell Weisberg Cancer Treatment Center

Detroit, Michigan, 48201, United States
Beijing Cancer Hospital

Beijing, Beijing Sheng, 100142, China
Centre Georges Francois Leclerc

Dijon, 21079, France
Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz

Besançon, 25000, France
Centre Hospitalier Universitaire Vaudois Lausanne

Lausanne, 1011, Switzerland
Centre Leon Berard

Lyon, 69008, France
Centre de Lutte contre le Cancer - Centre Oscar Lambret

Lille, 59000, France
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States
Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200025, China
Gustave Roussy

Villejuif, 94805, France
Hadassah University Hospital Ein Kerem

Jerusalem, 9112001, Israel
Hopital Foch

Suresnes, Île-de-France Region, 92150, France
Hopital Saint-Andre

Bordeaux, 33000, France
Hopital Saint-Antoine

Paris, 75012, France
Hopital de la Timone

Marseille, 13385, France
Hopitaux Universitaires de Geneve

Geneva, 1205, Switzerland
Inselspital Universitatsspital Bern

Bern, 3010, Switzerland
Institut de Cancerologie de lOuest - Saint-Herblain - Site Rene Gauducheau

Saint-Herblain, 44805, France
Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada
Kantonsspital Sankt Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland
Klinikum Wels-Grieskirchen

Wels, Upper Austria, 4600, Austria
Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom
Mary Crowley Cancer Research

Dallas, Texas, 75230, United States
Massachusetts General Hospital

Boston, Massachusetts, 02114, United States
McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada
Memorial Cancer Institute at Memorial Hospital West - Cancer Institute/Radiology Oncology

Gainesville, Florida, 32610, United States
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

Warsaw, Masovian Voivodeship, 02-034, Poland
National Cancer Center Hospital

Chuo-Ku, Tokyo, 104-0045, Japan
Norris Comprehensive Cancer Center

Los Angeles, California, 90089-1019, United States
Oxford University Hospitals NHS Foundation Trust

Oxford, Ox1 2JD, United Kingdom
PanOncology Trials: Universidad de Puerto Rico - Centro Comprensivo de Cancer

San Juan, 00936, Puerto Rico
Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada
Providence Portland Medical Center

Portland, Oregon, 97213, United States
Queen's University Belfast

Belfast, Northern Ireland, BT9 7BL, United Kingdom
Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States
SCRI - HealthOne Denver

Denver, Colorado, 80218-1238, United States
Sarah Cannon Research Institute (SCRI)

Nashville, Tennessee, 37203, United States
Shanghai East Hospital

Shanghai, Shanghai Municipality, 200123, China
Siteman Cancer Center - North County

Florissant, Missouri, 63031, United States
Siteman Cancer Center - South County

St Louis, Missouri, 63129, United States
Siteman Cancer Center - St. Peters

City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center - West County

Creve Coeur, Missouri, 63141, United States
Sixth Affiliated Hospital of Sun Yat-Sen University/Guangdong Gastrointestinal Hospital

Guangzhou, Guangzhou Sheng, 510655, China
Soroka Medical Center

Beersheba, 9457108, Israel
Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel
The Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel
UCI Health - Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States
University College London Hospitals NHS Foundation Trust

London, NW1 2BU, United Kingdom
University of California Los Angeles - Jonsson Comprehensive Cancer Center

Santa Monica, California, 90404-2023, United States
University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States
University of Cincinnati Health Barrett Cancer Center

Cincinnati, Ohio, 45019, United States
University of Cincinnati Health Barrett Cancer Center

Cincinnati, Ohio, 45219-2354, United States
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States
University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States
Virginia Cancer Specialists, P.C. - Fairfax

Fairfax, Virginia, 22031-2171, United States
Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, 63110-1032, United States
West Chester Hospital

West Chester, Ohio, 45069, United States
West China Hospital

Chengdu, Sichuan, 610041, China
West China School of Medicine - West China Hospital of Sichuan University

Chengdu, Sichuan, 610610, China
Yale Cancer Center

New Haven, Connecticut, 06519, United States
Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

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