Solid NeoplasmsPhase 1/2iintune-1NCT04420884
A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors
A Phase 1/2 study testing Dazostinag, Pembrolizumab and Platinum in people with Solid Neoplasms, run by Takeda at 62 sites in 11 countries.
Trial summary
The main aim of this study is to check if people with advanced solid tumors have side effects from dazostinag, and to check how much dazostinag they can receive without getting significant side effects from it when given alone and in combination with pembrolizumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Neoplasms
- What is being tested?
- Dazostinag, Pembrolizumab and Platinum
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 248 participants
- Where
- 62 sitesin 11 countries
- Study dates
- 22 Jul 2020to 30 Mar 2026
- Phase
- Phase 1/2
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.
- 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.
- 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.
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- Tumors that are naive to anti-PD-(L)-1 therapy.
- 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.
- 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.
- Adequate bone marrow, renal, hepatic and cardiac 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 Version 5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement therapy.
- 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.
- 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.
- 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.
Who cannot join
- 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.
- 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.
- Oxygen saturation less than (<) 92 percent (%) on room air at screening or during C0D1 (for Japan safety lead-in only) and C1D1 predose assessment.
- Treated with other STING agonists/antagonist and toll-like receptors agonists within the past 6 months.
- 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.
- History of brain and leptomeningeal metastasis unless:
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- Brain metastases are clinically and radiologically stable or improved (that is, ≥ 4 weeks) following surgery, whole-brain radiation, or stereotactic radiosurgery, AND
- Off corticosteroids.
- Ongoing Grade ≥ 2 infection or participants with Grade ≥ 2 fever of malignant origin.
- Chronic, active hepatitis (example: participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV]- ribonucleic acid [RNA]).
- For participants in the dose escalation SA Part 1A only: refusal of standard therapeutic options.
- For participants receiving pembrolizumab only: contraindication and/or intolerance to the administration of pembrolizumab.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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).
- 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).
- Recipients of allogeneic or autologous stem cell transplantation or organ transplantation.
- For Part 2 SCCHN only:
- Has progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced SCCHN.
- 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.
- 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.
- Participants with known dihydropyrimidine dehydrogenase (DPD) deficiency or thymidine phosphorylase gene (TYMP) mutations (Part 2B only).
Trial locations and contacts
62 sites in 11 countries.
62 sites in 11 countries
United States26 sites
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
University of Cincinnati Health Barrett Cancer Center
Cincinnati, Ohio, 45019
University of Cincinnati Health Barrett Cancer Center
Cincinnati, Ohio, 45219
Siteman Cancer Center - St. Peters
City of Saint Peters, Missouri, 63376
Siteman Cancer Center - West County
Creve Coeur, Missouri, 63141
Mary Crowley Cancer Research
Dallas, Texas, 75230
SCRI - HealthOne Denver
Denver, Colorado, 80218
Barbara Ann Karmanos Cancer Institute - Lawrence and Idell Weisberg Cancer Treatment Center
Detroit, Michigan, 48201
Virginia Cancer Specialists, P.C. - Fairfax
Fairfax, Virginia, 22031
Siteman Cancer Center - North County
Florissant, Missouri, 63031
Memorial Cancer Institute at Memorial Hospital West - Cancer Institute/Radiology Oncology
Gainesville, Florida, 32610
University of California San Diego Moores Cancer Center
La Jolla, California, 92093
Norris Comprehensive Cancer Center
Los Angeles, California, 90089
Sarah Cannon Research Institute (SCRI)
Nashville, Tennessee, 37203
Yale Cancer Center
New Haven, Connecticut, 06519
UCI Health - Chao Family Comprehensive Cancer Center
Orange, California, 92868
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Providence Portland Medical Center
Portland, Oregon, 97213
University of California Los Angeles - Jonsson Comprehensive Cancer Center
Santa Monica, California, 90404
Washington University School of Medicine Siteman Cancer Center
St Louis, Missouri, 63110
Siteman Cancer Center - South County
St Louis, Missouri, 63129
West Chester Hospital
West Chester, Ohio, 45069
France10 sites
Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz
Besançon, 25000
Hopital Saint-Andre
Bordeaux, 33000
Centre Georges Francois Leclerc
Dijon, 21079
Centre de Lutte contre le Cancer - Centre Oscar Lambret
Lille, 59000
Centre Leon Berard
Lyon, 69008
Hopital de la Timone
Marseille, 13385
Hopital Saint-Antoine
Paris, 75012
Institut de Cancerologie de lOuest - Saint-Herblain - Site Rene Gauducheau
Saint-Herblain, 44805
Hopital Foch
Suresnes, Île-de-France Region, 92150
Gustave Roussy
Villejuif, 94805
China7 sites
Beijing Cancer Hospital
Beijing, Beijing Sheng, 100142
West China Hospital
Chengdu, Sichuan, 610041
West China School of Medicine - West China Hospital of Sichuan University
Chengdu, Sichuan, 610610
Sixth Affiliated Hospital of Sun Yat-Sen University/Guangdong Gastrointestinal Hospital
Guangzhou, Guangzhou Sheng, 510655
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200025
Shanghai East Hospital
Shanghai, Shanghai Municipality, 200123
Israel4 sites
Soroka Medical Center
Beersheba, 9457108
Hadassah University Hospital Ein Kerem
Jerusalem, 9112001
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
The Chaim Sheba Medical Center
Tel Litwinsky, 52621
Switzerland4 sites
Inselspital Universitatsspital Bern
Bern, 3010
Hopitaux Universitaires de Geneve
Geneva, 1205
Centre Hospitalier Universitaire Vaudois Lausanne
Lausanne, 1011
Kantonsspital Sankt Gallen
Sankt Gallen, Canton of St. Gallen, 9007
United Kingdom4 sites
Queen's University Belfast
Belfast, Northern Ireland, BT9 7BL
Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF
University College London Hospitals NHS Foundation Trust
London, NW1 2BU
Oxford University Hospitals NHS Foundation Trust
Oxford, Ox1 2JD
Canada3 sites
Jewish General Hospital
Montreal, Quebec, H3T 1E2
McGill University Health Centre
Montreal, Quebec, H4A 3J1
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
Poland1 site
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
Warsaw, Masovian Voivodeship, 02-034
Puerto Rico1 site
PanOncology Trials: Universidad de Puerto Rico - Centro Comprensivo de Cancer
San Juan, 00936
About this study
Official title: An Open-label, Dose Escalation, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-676 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Advanced or Metastatic Solid Tumors
The main aim of this study is to check if people with advanced solid tumors have side effects from dazostinag, and to check how much dazostinag they can receive without getting significant side effects from it when given alone and in combination with pembrolizumab. The study will be conducted in two phases including a dose escalation phase and a dose expansion phase. In the dose escalation phase, escalating doses of dazostinag are being tested alone and in combination with pembrolizumab to treat participants who have advanced or metastatic solid tumors. In the dose expansion phase, dazostinag will be studied with pembrolizumab with or without chemotherapy in participants with untreated metastatic or recurrent, unresectable squamous cell carcinoma of head and neck (SCCHN) and in combination with pembrolizumab in third-line or later recurrent locally advanced or metastatic microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and third-line recurrent locally advanced or metastatic microsatellite stable/mismatch repair proficient (MSS/pMMR) colorectal cancer (CRC).
Read the detailed description
The drug being tested in this study is called dazostinag. Dazostinag is being tested to treat people who have advanced or metastatic solid tumors.
The study will enroll approximately 374 participants. Part 1 consists of an initial Safety Lead-in to Dose Escalation Phase; Part 2 and Part 3 compose the Expansion Phase in 2 specific indications namely, previously untreated metastatic or recurrent, unresectable SCCHN (Part 2) and third-line or later recurrent locally advanced or metastatic MSI-H/dMMR and third-line recurrent locally advanced or metastatic MSS/pMMR CRC (Part 3). Participants will be assigned to the following treatment groups in the respective Phases of the study:
- Part 1 (Dose Escalation Phase): Safety Lead-in + Dazostinag single agent (SA) [Part 1A] Dazostinag 0.1 milligram (mg) in the Safety Lead-in followed by Dazostinag as escalating doses (0.2 mg and above) in Part 1A
- Part 1B (Combination Dose Escalation Phase): Dazostinag as escalating doses (0.2 mg and above) + Pembrolizumab
- Japan Safety Lead-in: Dazostinag SA 5.0 mg in the Safety Lead-in± Pembrolizumab in Arms A and B. Additional dose levels of Dazostinag (such as 14.0 mg) in combination with pembrolizumab may be explored during the Japan safety lead-in considering recommended dose for expansion (RDE1) as 5.0 mg and dose optimization.
Once a safe dose is recommended from Part 1, participants of select advanced or metastatic solid tumors will receive dazostinag in below defined cohorts in the expansion phase:
- Part 2A (SCCHN Combined Positive Score [CPS] ≥ 1 Dose Expansion Phase): Dazostinag + Pembrolizumab*
- Part 2B (SCCHN Dose Expansion Phase): Dazostinag + Pembrolizumab + Chemotherapy
- Part 3A (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSI-H/dMMR CRC
- Part 3B (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSS/pMMR CRC
This multi-center trial will be conducted worldwide. The overall time to participate in this study is 68 months. Participants will make multiple visits to the clinic, including 30 days after last dose of study drug for a follow-up assessment. Participants in Parts 2 and 3 will be followed for survival for up to 12 months after the last dose of study drug.
- Conditions
- Solid Neoplasms
- Being tested
- Dazostinag, Pembrolizumab, Platinum, 5-fluorouracil
- Keywords
- Drug Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DazostinagDrug
Also called TAK-676
Dazostinag intravenous infusion.
PembrolizumabDrug
Pembrolizumab intravenous infusion.
PlatinumDrug
Carboplatin or Cisplatin intravenous infusion
5-fluorouracilDrug
5-fluorouracil intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1A (Monotherapy Dose Escalation Phase): Dazostinag Safety Lead-in Dazostinag SA (≤ 2.5 mg) | Experimental | Safety Lead-in: Participants received dazostinag, 0.1 milligrams (mg), infusion, intravenously (IV), once weekly (QW), on Days 1, 8 and 15 of 21-day treatment cycles. Following the safety lead-in dazostinag single agent (SA) dose escalation (Part 1A) was initiated: Participants received doses up to and including 2.5 mg dazostinag SA, infusion, IV, QW, on Days 1, 8 and 15 of 21-day treatment cycle. Receives: Drug: Dazostinag |
| Part 1A (Monotherapy Dose Escalation Phase): Dazostinag SA 3.5 mg | Experimental | Participants received 3.5 mg dazostinag SA, infusion, IV, QW, on Days 1, 8 and 15 of 21-day treatment cycle. Receives: Drug: Dazostinag |
| Part 1A (Monotherapy Dose Escalation Phase): Dazostinag SA 5.0 mg | Experimental | Participants received 5.0 mg dazostinag SA, infusion, IV, QW, on Days 1, 8 and 15 of 21-day treatment cycle. Receives: Drug: Dazostinag |
| Part 1A (Monotherapy Dose Escalation Phase): Dazostinag SA 7.0 mg | Experimental | Participants received 7.0 mg dazostinag SA, infusion, IV, QW, on Days 1, 8 and 15 of 21-day treatment cycle. Receives: Drug: Dazostinag |
| Part 1A (Monotherapy Dose Escalation Phase): Dazostinag SA 9.0 mg | Experimental | Participants received 9.0 mg dazostinag SA, infusion, IV, QW, on Days 1, 8 and 15 of 21-day treatment cycle. Receives: Drug: Dazostinag |
| Part 1A (Monotherapy Dose Escalation Phase): Dazostinag SA 10.5 mg | Experimental | Participants received 10.5 mg dazostinag SA, infusion, IV, QW, on Days 1, 8 and 15 of 21-day treatment cycle. Receives: Drug: Dazostinag |
| Part 1A (Monotherapy Dose Escalation Phase): Dazostinag SA 14.0 mg | Experimental | Participants received 14.0 mg dazostinag SA, infusion, IV, QW, on Days 1, 8 and 15 of 21-day treatment cycle. Receives: Drug: Dazostinag |
| Part 1B (Combination Dose Escalation Phase): ≤ 2.5 mg Dazostinag + Pembrolizumab | Experimental | Participants received ≤ 2.5 mg dazostinag infusion, IV, QW, on Days 1, 8, and 15 of a 21-day cycle along with pembrolizumab 200 mg infusion, IV, once every 3 weeks (Q3W) on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
| Part 1B (Combination Dose Escalation Phase): 3.5 mg Dazostinag + Pembrolizumab | Experimental | Participants received 3.5 mg dazostinag infusion, IV, QW, on Days 1, 8, and 15 of a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
| Part 1B (Combination Dose Escalation Phase): 5.0 mg Dazostinag + Pembrolizumab | Experimental | Participants received 5.0 mg dazostinag infusion, IV, QW, on Days 1, 8, and 15 of a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
| Part 1B (Combination Dose Escalation Phase): 7.0 mg Dazostinag + Pembrolizumab | Experimental | Participants received 7.0 mg dazostinag infusion, IV, QW, on Days 1, 8, and 15 of a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
| Part 1B (Combination Dose Escalation Phase): 9.0 mg Dazostinag + Pembrolizumab | Experimental | Participants received 9.0 mg dazostinag infusion, IV, QW, on Days 1, 8, and 15 of a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
| Part 1B (Combination Dose Escalation Phase): 10.5 mg Dazostinag + Pembrolizumab | Experimental | Participants received 10.5 mg dazostinag infusion, IV, QW, on Days 1, 8, and 15 of a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
| Part 1B (Combination Dose Escalation Phase): 14.0 mg Dazostinag + Pembrolizumab | Experimental | Participants received 14.0 mg dazostinag infusion, IV, QW, on Days 1, 8, and 15 of a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
| Part 2A SCCHN Dose Expansion Phase): Dazostinag + Pembrolizumab | Experimental | Participants with SCCHN received dazostinag 5.0 mg, infusion, IV, on Days 1, 8, and 15 of a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
| Part 2B (SCCHN Dose Expansion Phase): Dazostinag + Pembrolizumab+ Chemotherapy | Experimental | Participants with SCCHN received dazostinag 5.0 mg, infusion, IV, on Days 1, 8, and 15 of a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. They also received platinum-based chemotherapy comprising the combination of carboplatin (target area under the curve of 5 milligrams per milliliter per minute (mg/mL/minute) [AUC 5]) or cisplatin (100 milligrams per square meter [mg/m^2]) on Day 1 of each treatment cycle, and 5-fluorouracil (5-FU) (1000 mg/m^2 per day for 4 consecutive days); Q3W from Day 1 to Day 4 of a 21-day cycle after dazostinag administration for up to 6 cycles. Receives: Drug: Dazostinag; Drug: Pembrolizumab; Drug: Platinum; Drug: 5-fluorouracil |
| Part 3A (CRC Dose Expansion Phase): Dazostinag + Pembrolizumab in MSI-H/dMMR CRC | Experimental | Participants with MSI-H/dMMR CRC received dazostinag 5.0 mg, infusion, IV, on Days 1, 8, and 15 of a 21-day cycle, along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
| Part 3B (CRC Dose Expansion Phase ): Dazostinag + Pembrolizumab in MSS/pMMR CRC | Experimental | Participants with MSS/pMMR CRC received dazostinag 5.0 mg, infusion, IV, on Days 1, 8, and 15 of a 21-day cycle, along with pembrolizumab 200 mg infusion, IV, Q3W on Day 1 of a 21-day cycle one hour prior to dazostinag. Receives: Drug: Dazostinag; Drug: Pembrolizumab |
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 Grade 3 or Higher TEAEs
Adverse Event (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: Up to approximately 68 months
Number of Participants With Dose-Limiting Toxicities (DLTs) During the Dose Escalation Phase
DLTs were defined as any TEAEs, that occurred during Cycle 1 and were evaluated according to the NCI CTCAE, Version 5.0.
Measured: During Cycle 1 (cycle length= 21 days)
Number of Participants Reporting One or More Treatment-emergent Serious Adverse Event (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: Up to approximately 68 months
Number of Participants With One or More TEAEs Leading to Dazostinag Dose Modifications and Treatment Discontinuations
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: Up to approximately 68 months
Secondary outcomes (8)
Overall Response Rate (ORR)
ORR was the percentage of participants who achieved confirmed complete response (cCR) or confirmed partial response (cPR) (determined by the investigator) during the study 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 less than (<) 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 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Measured: Up to approximately 68 months
Disease Control Rate (DCR)
DCR was the percentage of participants who achieved cCR, cPR, or stable disease (SD) for more than or equal to (≥) 6 weeks during the study according to RECIST, V1.1. CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in sum of LD of target lesions, taking as a reference the Baseline LD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: Up to approximately 68 months
Duration of Response (DOR)
DOR was the time from the date of first documentation of a cPR or better to the date of first documentation of PD per RECIST V1.1 or death for responders (cPR or better), whichever occurred first. Responders without documentation of PD or death were censored at the date of last response assessment that was SD or better. DOR was analyzed using the Kaplan-Meier method.
Measured: Up to approximately 68 months
Time to Response (TTR)
TTR was defined as the time from the date of first dose administration to the date of first documented cPR or better by the investigator according to RECIST V1.1. TTR was analyzed using the Kaplan-Meier method.
Measured: Up to approximately 68 months
Expansion Phase Only: Progression-Free Survival (PFS)
Progression-free survival was the time from the date of first dose administration to the date of first documentation of PD per RECIST V1.1 or death due to any cause, whichever occurred first. PD for target lesions was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. PD for nontarget lesions was defined as unequivocal progression of existing nontarget lesions.
Measured: Up to approximately 29 months
Expansion Phase Only: Overall Survival (OS)
OS was defined as the time from the date of first dose administration to the date of death.
Measured: Up to approximately 29 months
Expansion Phase Only: OS Rate at 6 Months
OS rate at 6 months was defined as the percentage of participants alive 6 months after the date of first dose administration. OS rate at 6 months was analyzed using the Kaplan-Meier (KM) estimate.
Measured: At 6 months
Expansion Phase Only: OS Rate at 12 Months
OS rate at 12 months was defined as the percentage of participants alive 12 months after the date of first dose administration. OS rate at 12 months was analyzed using the KM estimate.
Measured: At 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start22 Jul 2020
- Primary completion30 Mar 2026
- Study completion30 Mar 2026
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 (2)Papers the sponsor has linked to this study.
- Other trials for Solid NeoplasmsStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 248 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04420884
- Sponsor's protocol ID
- TAK-676-1002
- Other IDs
- U1111-1241-4427, 2023-505627-30-00, jRCT2031230532, 2023
- Acronym
- iintune-1
- Status last verified
- Oct 2026
- First submitted
- 4 Jun 2020
- Last updated
- 22 Oct 2026
- 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 41888610Carideo 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