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

NCT ID NCT04381650

Disease control Sponsor: Takeda Source: ClinicalTrials.gov ↗

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

Summary

This study tested a new drug, TAK-981, combined with the immunotherapy pembrolizumab in 161 adults with advanced or metastatic solid tumors that could not be cured. The main goals were to check safety and see if the combination could shrink tumors. Participants received treatment in 21-day cycles for up to 24 months.

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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

161 people

The number who actually took part.

Started

Aug 2020

Finished

Oct 2024

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. Has a histologically or cytologically documented, advanced (metastatic and/or unresectable) cancer as listed below that is incurable: Note: Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line standard of care treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence. A. Non-squamous NSCLC for which prior standard first-line treatment containing an anti-programmed cell death protein 1/programmed cell death protein 1 ligand (PD-1/PD-L1) checkpoint inhibitor (CPI) alone or in combination has failed and that has progressed on no more than 1 prior systemic therapy. In Phase 2, participants with nonsquamous NSCLC must have not received more than 1 prior systemic therapy and must not have presented with disease progression during the first 6 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy. Note: In Phase 1, participants with nonsquamous NSCLC and known driver mutations/genomic aberrations (e.g., epidermal growth factor receptor (EGFR), B-Raf proto-oncogene mutation V600E \[BRAF V600E\], and ROS proto-oncogene 1 \[ROS1\] sensitizing mutations, neurotrophic receptor tyrosine kinase \[NRTK\] gene fusions, and anaplastic lymphoma kinase \[ALK\] rearrangements) must have also shown progressive disease after treatment with a commercially available targeted therapy. In Phase 2, participants with driver mutations are not eligible. B. CPI-naive cervical cancer (squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix) participants for whom prior standard first-line treatment has failed and who have received no more than 1 prior systemic line of therapy for recurrent or Stage IVB cervical cancer. Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric-type adenocarcinoma, clear-cell carcinoma, and mesonephric carcinoma. Histologic confirmation of the original primary tumor is required via pathology report. Note: First-line treatment must have consisted of platinum-containing doublet. Chemotherapy administered concurrently with primary radiation (e.g., weekly cisplatin) is not counted as a systemic chemotherapy regimen. C. CPI-naïve microsatellite stable-colorectal cancer (MSS-CRC) participants for whom prior standard first-line treatment has failed and who have progressed on no more than 3 chemotherapy regimens. Note: Participants must have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens if indicated. D. Unresectable Stage III or Stage IV cutaneous melanoma that has not received prior therapy in the metastatic setting. Note: Participants with acral melanoma are not eligible. Participants who have presented with disease relapse after ≥6 months of the last dose of CPI or BRAF-mitogen-activated protein kinase kinase (MEK) inhibitor in the adjuvant setting are eligible. E. Squamous NSCLC for which prior standard first-line treatment containing an anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed. Participant must have not received more than 1 prior systemic therapy and must not have presented with disease progression during the first 6 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy. F. Squamous or nonsquamous NSCLC for which prior standard first-line treatment containing an anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed within 6 months from the initiation of the CPI. Participants must not have received more than 1 prior systemic therapy in the metastatic setting. Note: Participants with driver mutations are not eligible. 2. Has at least 1 radiologically measurable lesion based on RECIST, Version 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 3. Has a performance status of 0 or 1 on the Eastern Cooperative Group Oncology (ECOG) Performance Scale. 4. Has left ventricular ejection fraction (LVEF) ≥40%; as measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan. 5. Has recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela. Note: Has a neuropathy ≤Grade 2, any grade alopecia, or autoimmune endocrinopathies with stable replacement therapy are permitted. 6. Demonstrate adequate organ function as described below: A. Platelet count ≥75.0 × 10\^9/L. B. Absolute neutrophil count (ANC) ≥1.0 × 10\^9/L. C. Hemoglobin ≥85 g/L (red blood cell \[RBC\] transfusion allowed ≥14 days before assessment). D. Calculated creatinine clearance ≥30 mL/min using the Cockcroft-Gault formula. E. Aspartate aminotransferase (AST, GOT) and alanine aminotransferase (ALT, GPT) ≤3.0 times the upper limit of normal (ULN), \<5.0 times the ULN if liver enzyme elevations are due to liver metastases; bilirubin ≤1.5 times the ULN. Participants with Gilbert's syndrome may have a bilirubin level \>1.5 times the ULN, per discussion between the investigator and the medical monitor. Exclusion Criteria: 1. History of uncontrolled brain metastasis (evidence of progression by imaging over a period of 4 weeks and/or neurologic symptoms that have not returned to baseline). Participant with treated brain metastases are allowed provided they are radiologically stable, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. Note: For asymptomatic participants, screening brain imaging is not required. 2. Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy. 3. Major surgery ≤14 days from the first dose of study drug and not recovered fully from any complications from surgery. 4. History of immune-related AEs related to treatment with immune CPIs that required treatment discontinuation. 5. Receiving or requires the continued use of medications that are known to be strong or moderate inhibitors and inducers of cytochrome P-450 (CYP) 3A4/5 and strong P-glycoprotein (Pgp) inhibitors. 6. Baseline prolongation of the QT interval corrected using Fridericia's formula (QTcF) (e.g., repeated demonstration of QTcF interval \>480 milliseconds (ms), history of congenital long QT syndrome, or torsades de pointes). 7. Has a history of autoimmune disease requiring systemic immunosuppressive therapy with daily doses of prednisone \>10 mg/day or equivalent doses, or any other form of immunosuppressive therapy. Hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for thyroid, adrenal or pituitary insufficiency) for endocrinopathies are not considered prohibited forms of systemic treatment of an autoimmune disease. 8. Has a history of noninfectious pneumonitis that required steroids or a history of interstitial lung disease. 9. Has an evidence of active, non-infectious pneumonitis. 10. Has a history of allogeneic tissue or solid organ transplant. 11. Has an active infection requiring systemic therapy. 12. Has a known history of human immunodeficiency virus (HIV) infection or any other relevant congenital or acquired immunodeficiency. 13. Has a known hepatitis B virus surface antigen seropositive or detectable hepatitis C infection viral load. Note: Participants who have positive hepatitis B core antibody or hepatitis B surface antigen antibody can be enrolled but must have an undetectable hepatitis B viral load. 14. History of any of the following ≤6 months before first dose: congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias \>Grade 2, pulmonary embolism or symptomatic cerebrovascular events, or any other serious cardiac condition (e.g., pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed. 15. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or has compromised ability to provide written informed consent.

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Conditions

The condition(s) this trial relates to.

cervical cancer colorectal cancer cutaneous melanoma metastatic malignant neoplasm non-small cell lung carcinoma non-small cell squamous lung carcinoma

As listed by the trial registrant

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

Advanced or metastatic solid tumors

Contacts and locations

Locations

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States
Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy

Bydgoszcz, 85-796, Poland
Centrum Terapii Wspolczesnej

Lodz, Łódź Voivodeship, 90-242, Poland
Cetus Hospital Dia Oncologia

Belo Horizonte, 30110-140, Brazil
Clinical Hospital Centre Osijek

Osijek, 31000, Croatia
Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States
Fundacao Pio XII Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-370, Brazil
General Hospital Pula

Pula, 52100, Croatia
Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States
HonorHealth

Scottsdale, Arizona, 85258, United States
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil
Hospital de Base Da Faculdade de Medicina de Sao Jose Do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil
Hospital de Clinicas de Porto Alegre (HCPA) - PPDS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, Kaunas County, LT-50161, Lithuania
Hospital of Lithuanian University of Health Sciences Kauno klinikos

Kaunas, Kaunas County, LT-50161, Lithuania
INCA Instituto Nacional de Cancer

Rio de Janeiro, 20230-230, Brazil
Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira

Rio de Janeiro, 20941-150, Brazil
Instituto de Oncologia Do Parana

Curitiba, Paraná, 80530-010, Brazil
Instytut Medyczny Santa Familia Sp. z o. o.

Lodz, 90-302, Poland
Kantonsspital Muensterlingen

Münsterlingen, Thurgau (de), 8596, Switzerland
Kantonsspital Winterthur

Winterthur, Zurich (de), 8400, Switzerland
Klinicki bolnicki centar Zagreb

Zagreb, City of Zagreb, 10000, Croatia
Med-Polonia Sp. z o.o.

Poznan, 60-569, Poland
Montefiore Einstein Cancer Center - BRANY - PPDS

The Bronx, New York, 10461, United States
Morristown Medical Center

Morristown, New Jersey, 07960, United States
National Cancer Center East

Kashiwa-Shi, Chiba, 277-0882, Japan
National Cancer Center Hospital

Chuo-Ku, Tokyo, 104-0045, Japan
National Cancer Institute

Vilnius, Vilnius County, LT-08660, Lithuania
ONCOSITE Centro de Pesquisa Clinica Em Oncologia

Ijuí, Rio Grande do Sul, 98700-000, Brazil
Pauls Stradins Clinical University Hospital

Riga, LV-1002, Latvia
Providence Cancer Institute, Franz Clinic

Portland, Oregon, 97213, United States
Riga East Clinical University Hospital Latvian Oncology Center

Riga, LV-1079, Latvia
START South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States
Specjalistyczna Praktyka Lekarska Slawomir Mandziuk

Lublin, 20-362, Poland
Stanford Cancer Institute (SCI)

Stanford, California, 94305, United States
Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China
The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Chuo-Ku, Tokyo, 104-0045, Japan
The Center for Cancer and Blood Disorders - PPDS

Bethesda, Maryland, 20817, United States
The First Affiliated Hospital, Zhejiang University School of Medicine - PPDS

Hangzhou, Zhejiang, 310003, China
UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15213, United States
Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, China
Universitaetsspital Bern - Inselspital

Bern, 3010, Switzerland
University Hospital Centre Split

Split, 21000, Croatia
University of California Irvine Medical Center

Orange, California, 92868, United States
University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States
University of Oklahoma Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States
University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States
University of Virginia Health System

Charlottesville, Virginia, 22908, United States
Uniwersyteckie Centrum Kliniczne-Ul. Smoluchowskiego 17

Gdansk, Pomeranian Voivodeship, 80-214, Poland
Virginia Cancer Specialists (Fairfax) - USOR

Fairfax, Virginia, 22031, United States
Warminsko-Mazurskie Centrum Chorob Pluc w Olsztynie

Olsztyn, 10-357, Poland
Yale Cancer Center

New Haven, Connecticut, 06520, United States

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