A Study of TAK-186 (Also Known as MVC-101) in Adults With Advanced or Metastatic Cancer

NCT 04844073

Brief Summary

Inclusion Criteria:

• Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status of ≤ 1
• Ability to provide informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. and documentation of informed consent before initiation of any study-related tests or procedures that are not part of standard of care for the participant’s disease. Participants must also be willing and able to comply with study procedures, including the acquisition of specified research specimens.
• Life expectancy ≥ 12 weeks
• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria and documented by Computed tomography (CT) and/or magnetic resonance imagingtests that create detailed images of areas inside the body (MRI). The definitions for measurable lesions are the same whether conventional and modified RECIST criteria are applied. Cutaneous or subcutaneousunder the skin lesions must be measurable by calipers. Lesions to be used as measurable disease for the purpose of response assessment must either a) not reside in a field that has been subjected to prior radiotherapy, or b) have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and before study enrollment or c) have been radiated at least 6 months before study enrollment.
  • Tumor Histology Types:
• Participants with pathologically proven, unresectable, locally advanced or metastatic solid tumors that based on literature reports are considered to express EGFR. During cohort expansion, participants with locally advanced or metastatic solid tumors expressing EGFR including advanced or metastatic NSCLC, CRC, and HNSCC are eligible for enrollment.* Tumors During Cohort Expansion:
• Participants with pathologically proven, unresectable, locally advanced or metastatic solid tumors that based on literature reports are considered to express EGFR are eligible for enrollment:
  • NSCLC: locally advanced or metastatic NSCLC that has progressed during or following treatment with platinum-based chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells, a checkpoint inhibitor (unless known to be PD-L1 negative), or targeted therapymedication that targets specific molecular features of cancer cells (for participants with a known actionable mutation).
  • CRC: locally advanced or metastatic CRC that has progressed after systemic therapies, including irinotecan, oxaliplatin, an anti-EGFR inhibitor (if K-RAS or N-RAS is WT), a checkpoint inhibitor (if MSI-H), and a VEGF inhibitor (if locally approved and accessible as a standard-of-care).
  • HNSCC: HNSCC that has progressed during or following treatment with a checkpoint inhibitor (unless ineligible, e.g, PD-L1 negative) and platinum-based chemotherapy (unless ineligible for or intolerant to platinum-based chemotherapy) with or without cetuximab for metastatic or recurrent disease.
    1. Participants with salivary gland tumors will not be considered as having HNSCC.
    2. Participants who refuse surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence for potentially curable disease where the surgery or radiotherapy could result in severe morbidity are eligible. The reason for the refusal will be captured in the electronic case report form (eCRFs).
       • Archival Tissuea group of cells that work together to perform a function:
• Participants must allow acquisition of existing formalin-fixed paraffin-embedded (FFPE) archival tumor sample, either a block or unstained slides. Participants who provide fresh pretreatment biopsyremoval of a section of tissue to analyse for cancer cells samples will not be required to submit archival tumor samples.
  • Tumor Biopsy:• Participants must be willing to consent to mandatory pretreatment (during screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening) and on-treatment fresh tumor biopsies for cohort expansion phase and backfill in dosethe amount of medication taken escalation. Once the target number of biopsies have been collected, additional paired pretreatment and on-treatment biopsies will not be required; sample collection will be optional after this time point. For fresh tumor biopsies, the lesion must be accessible (those occurring outside the brain or those that are accessible by an interventional or endoscopic procedure) for a low-risk biopsy procedure that does not place the participant at an unjustifiable riskthe possibility that something bad will happen in the opinion of the investigator. Participants who have an archived biopsy specimena sample for investigating (e.g. blood, stools, urine, sputum etc.) available that was obtained up to 90 days prior to treatment initiation and have received no other treatment from the time of biopsy until the start of treatment with TAK-186, may submit that archived specimen in lieu of a pretreatment biopsy upon agreement from the sponsor.
  • Laboratory Features:
• Acceptable laboratory parameters as follows:
  1. Albumin ≥ 3.0 g/dL
  2. Platelet count ≥ 75 × 103/μL
  3. Hemoglobin ≥ 9.0 g/dL
  4. Absolute neutrophil count ≥ 1.0 × 103/μL
  5. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN); for participants with hepatic metastases, ALT/AST ≤ 5 × ULN
  6. Total bilirubin ≤ 1.5 × ULN, except participants with Gilbert’s syndrome, who may enroll if the conjugated bilirubin is within normal limits.
  7. Creatinine clearance of ≥ 30 mL/minute using Cockcroft-Gault equation.
     • Reproductive Features:
• WOCBP must have a negative serum pregnancy test performed within 72 hours before the initiation of study drug administration. WOCBP must use 1 form of highly effective method and 1 additional effective (barrier) method of contraception at the same time throughout the study, starting at screening through 90 days after the last dose of TAK-186. Contraception methods may be considered highly effective if they can achieve a failure rate of less than 1% per year when used consistently and correctly.
• Male participants with partners of childbearing potential must use barrier contraception during the entire study treatment period through 120 days after the last dose of study drug and must not donate sperm during this period. In addition, male participants should also have their partners use contraception (as documented for female participants) for the same period of time.* Previous Checkpoint Inhibitor Therapy:
• Participants who have previously received an immune checkpoint before enrollment must have checkpoint inhibitor immune-related toxicity resolved to either Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells ≤ 1 or baseline
• Symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet the following criteria at the time of enrollment:
  1. No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroidsa type of anti-inflammatory medication that is used to treat inflammation ≥ 10 mg prednisone per day or equivalent).
  2. No concurrent leptomeningeal disease or spinal cord compression.