MARGARET: Testing a new drug (called TAS0953/HM06) in people with advanced cancers that have RET gene changes, to find a safe dose and see how well it worksPhase I/II Study of the Selective RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities

Inclusion

Ages Eligible for Study:

- Adult patient (The definition of adulthood shall comply with the regulatory requirements of each region)

Inclusion Criteria:

Phase I - Common inclusion criteria for Dose-Escalation / Dose-Expansion:

• Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
• Available RET-gene abnormalities determined on tissue biopsy or liquid biopsy. If deemed appropriate by the investigator, determination on a pleural cell block or cell pellet is also acceptable.
• Adequate hematopoietic, hepatic and renal function

Phase I Dose-Escalation - Specific inclusion criteria:

• Advanced solid tumors
• Measurable and/or non-measurable disease as determined by RECIST 1.1
• If patient has brain and/or leptomeningeal metastases, (s)he should be asymptomatic.

Phase I Dose-Expansion - Specific inclusion criteria:

• Patient with RET gene fusion :

  • Cohort 1, 3: locally advanced or metastatic NSCLC patients naïve to RET selective inhibitors and no prior systemic anti-cancer treatment. Patients who have been treated with neo-adjuvant or adjuvant chemotherapy may be included if it has been completed at least 6 months prior to the first dose of the study.
  • Cohort 2, 4: locally advanced or metastatic NSCLC patients with RET gene fusion and prior exposure to RET selective inhibitors.
• Measurable disease as determined by RECIST 1.1

• If patient has brain and/or leptomeningeal metastases,(s)he should have:

  • asymptomatic untreated brain/leptomeningeal metastases off steroids and anticonvulsant for at least 7 days or
  • asymptomatic brain metastases already treated with local therapy and be clinically stable on steroids and anticonvulsant for at least 7 days before study drug administration.

Phase II :

• Available RET-gene abnormalities determined on tissue or liquid biopsy

• Locally advanced or metastatic:

  • NSCLC patients with primary RET gene fusion and prior exposure to RET selective inhibitors;
  • NSCLC patients with RET gene fusion and without prior exposure to RET selective inhibitors
  • patients with advanced solid tumors that harbour RET gene abnormalities (other than NSCLC patients with primary RET gene fusions) and has failed all the available therapeutic options
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
• Measurable disease as determined by RECIST 1.1

• If patient has brain and/or leptomeningeal metastases,(s)he should have:

  • asymptomatic untreated brain/leptomeningeal metastases off steroids and anticonvulsant for at least 7 days or
  • asymptomatic brain metastases already treated with local therapy and be clinically stable on steroids and anticonvulsant for at least 7 days before study drug administration.
• Adequate hematopoietic, hepatic and renal function