A Study to Evaluate the Safety, Tolerability, and Antitumor Activity of TAK-981 Plus Pembrolizumab in Patients With Select Advanced or Metastatic Solid Tumors
- Conditions
- Advanced or Metastatic Solid TumorsMedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004325-23-LT
- Lead Sponsor
- Takeda Development Center Americas, Inc. (TDC Americas)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 231
1.Adult male or female patients aged 18 years or older.
2.Be willing and able to provide written informed consent for the study.
3.Have a histologically or cytologically documented, advanced (metastatic and/or unresectable) cancer as listed below that is incurable:
• A: Non-squamous NSCLC.
• B: Cervical cancer.
• C: MSS-CRC.
• D: Cutaneous melanoma.
• E: Squamous NSCLC.
Note: For further details, please refer to protocol.
4.Have 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.
5.Patients in Phase 2 expansion cohorts must have a PD-L1 result in tumor tissue obtained from an FDA-approved PD-L1 test.
6.Willing to consent to mandatory pre-treatment fresh tumor biopsy for Phase 2.
7.Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
8.Demonstrate adequate organ function as described below:
A.Platelet count =75.0 × 109/L.
B.Absolute neutrophil count (ANC) =1.0 × 109/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 × upper limit of normal (ULN), <5.0 times the ULN if liver enzyme elevations are due to liver metastases; bilirubin =1.5 × ULN. Patients with Gilbert's syndrome may have a bilirubin level >1.5 × ULN, per discussion between the investigator and the medical monitor.
9.Left ventricular ejection fraction (LVEF) =40%; as measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
10.Have recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela.
11.Women of childbearing potential must have a negative serum/urine pregnancy test within 72 hours prior to receiving the first dose of study medication.
12.Female patients must meet 1 of the following:
A.Postmenopausal for at least 1 year before the screening visit, or
B.Surgically sterile, or
C.If they are of childbearing potential, agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception at the same time, from the time of signing of the ICF through 6 months after the last dose of study, or
D.Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
13.Male patients, even if surgically sterilized (ie, status postvasectomy) must agree to 1 of the following:
A.Agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or
B.Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
14.Must be willing and able to comply with clinic visits and procedures outlined in the study protocol.
1. Received treatment with systemic anticancer treatments or investigational products within 14 days before the first dose of study drug or 5 half-lives, whichever is shorter.
2. 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). Patients 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.
3. 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 patient is not on active anticancer therapy.
4. Major surgery =14 days from the first dose of study drug and not recovered fully from any complications from surgery.
5. Prior treatment with TAK-981.
6. Hypersensitivity to TAK-981, pembrolizumab, or any component of the drug product.
7. Baseline prolongation of the QT interval corrected using Fridericia’s formula (QTcF) (eg, repeated demonstration of QTcF interval >480 ms, history of congenital long QT syndrome, or torsades de pointes).
8. History of immune-related AEs related to treatment with immune CPIs that required treatment discontinuation.
9. Receiving or requires the continued use of medications that are known to be strong or moderate inhibitors and inducers of CYP3A4/5 and strong P-glycoprotein (Pgp) inhibitors. To participate in this study, such patients should discontinue use of such agents for at least 2 weeks (1 week for CYP3A4/5 and Pgp inhibitors) before receiving a dose of TAK-981.
10. Receipt of any live vaccine within 4 weeks of initiation of study treatment.
11. 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 (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) ) for endocrinopathies are are not considered prohibited forms of systemic treatment of an autoimmune disease.
12. History of noninfectious pneumonitis that required steroids or a history of interstitial lung disease.
13. Has evidence of active, noninfectious pneumonitis.
14. History of allogeneic tissue or solid organ transplant.
15. Has active infection requiring systemic therapy.
16. Known history of HIV infection or any other relevant congenital or acquired immunodeficiency.
17. Known hepatitis B virus surface antigen seropositive or detectable hepatitis C infection viral load.
18. 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 (eg, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
19. Psychiatric illness/social circumstances that would limit compliance w
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method