A Dose Escalation Study of MLN7243 (TAK-243) in Adult Participants With Advanced Solid Tumors
Condition: Advanced Malignant Solid Tumors
MeSH terms: Neoplasms
Intervention: MLN7243
Intervention description: Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.
Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.
Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to evaluate safety and tolerability (establish maximum tolerated
      dose [MTD], inform the recommended phase 2 dose [RP2D], and identify the dose-limiting
      toxicities [DLTs]) of MLN7243.
    

Eligibility criteria:

        Inclusion Criteria

        Each participant must meet all of the following inclusion criteria to be enrolled in the
        study:

          1. Male or female participants 18 years or older.

          2. Participants must have a histologically confirmed diagnosis of an advanced, metastatic
             malignant solid tumor and must have failed or exhausted standard therapies or for
             which no standard therapy is available.

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          4. Participants with adequate hematologic and organ function.

          5. All participants must have radiographically detectable tumors with measurable disease
             as defined by RECIST (version 1.1).

          6. Participants undergoing a biopsy procedure must have accessible lesions which are safe
             to biopsy.

          7. Recovered (that is, less than or equal to (<=) Grade 1 toxicity) from the reversible
             effects of prior antineoplastic therapy, except alopecia.

          8. Female participants who are postmenopausal for at least 1 year before the screening
             visit, surgically sterile, or agree to practice 2 effective methods of contraception,
             at the same time, from the time of signing the informed consent form through 4 months
             after the last dose of study drug, or agree to practice true abstinence.

             Male participants who agree to practice effective barrier contraception during the
             entire study treatment period through 4 months after the last dose of study drug or
             agree to practice true abstinence.

          9. Suitable venous access for the study-required blood sampling including PK sampling.

        Exclusion Criteria

        Participants meeting any of the following exclusion criteria are not to be enrolled in the
        study:

          1. Participants with clinically significant pre-existing cardiac impairment.

          2. Participants homozygous for the ABCG2 (BCRP) c.421C greater than (>) 1 A polymorphism
             will be excluded from the study until the safety of a minimum of the first 3 dose
             levels has been characterized and the sponsor confirms that such participants can be
             enrolled at doses that are at least 3-fold lower than the most recently determined
             safe and tolerable dose among at least 3 dose limiting toxicities (DLT)-evaluable
             non-homozygous participants.

          3. Participants with known active central nervous system (CNS) lesions are excluded.
             Systemic antineoplastic therapy or investigational agents within 21 days before the
             first dose of study drug.

          4. Radiotherapy within 14 days before the first dose of study drug is not allowed except
             for limited field radiotherapy for palliative bone pain.

          5. For participants where tumor biopsies are required or requested:

               -  Any known coagulation abnormalities that would contraindicate the tumor biopsy
                  procedure.

               -  Ongoing therapy with any anticoagulant or antiplatelet agents (example, aspirin,
                  clopidogrel [Plavix®], heparin, or warfarin).

          6. Major surgery within 28 days before the first dose of MLN7243.

          7. Life-threatening illness unrelated to cancer.

          8. Any evidence of active infection or antibiotic therapy within 14 days before the first
             dose of MLN7243.

          9. Known human immunodeficiency virus (HIV) positivity or AIDS-related illness, hepatitis
             B virus, and hepatitis C virus.

         10. Participants whose weight is less than (<) 40 kilogram (kg).

         11. History of uncontrolled sleep apnea syndrome and other conditions that could result in
             excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.

         12. Female participants who are lactating and breastfeeding or have a positive serum
             pregnancy test during the Screening period or a positive urine pregnancy test on Day 1
             before first dose of study drug.