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A Study of TAK-981 Given With Pembrolizumab in Participants With Select Advanced or Metastatic Solid Tumors

Phase 1
Recruiting
Conditions
Advanced or Metastatic Solid Tumors
Registration Number
JPRN-jRCT2031210417
Lead Sponsor
akayama Ippei
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
231
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 non-small cell lung cancer (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. For the Phase1b Japan-specific Lead-in, non-squamous NSCLC that has progressed to no more than 1 prior systemic immune CPI/anti-PD-(1/L1)-containing 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. For the Phase1b Japan-specific Lead-in, CPI-naive cervical cancer (squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix) patients for whom prior standard first-line treatment for recurrent or Stage IVB cervical cancer has failed.
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-naive 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.
For the Phase1b Japan-specific Lead-in, MSS-CRC patients who have no standard therapeutic option with a proven clinical benefit, are intolerant, or have refused them.
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 kin

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 adverse events (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 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 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 (eg, 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.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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