Study of RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities

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 or liquid biopsy
• Documented progression of disease following existing therapies deemed by the Investigator to have demonstrated clinical benefit or unable to receive such therapies.
• 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:

• Locally advanced or metastatic non small cell lung cancer (NSCLC) patients with primary 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

Exclusion Criteria

Common exclusion criteria for Phase 1 and Phase 2

• Investigational agents or anticancer therapy within 5 half-lives prior to the first dose of study drug
• Major surgery (excluding placement of vascular access) within 4 weeks prior to the first dose of study drug or planned major surgery during the course of study treatment.
• Whole Brain Radiotherapy within 14 days or other palliative radiotherapy within 7 days prior to the first dose of study drug, or persisting side effects of such therapy, in the opinion of the Investigator.
• Clinically significant, uncontrolled, cardiovascular disease including myocardial infarction within 3 months prior to Day 1 of Cycle 1, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III-IV, and severe uncontrolled arterial hypertension, according to the Investigator's opinion.
• QT interval corrected using Fridericia's formula (QTcF) >470 msec; personal or family history of prolonged QT syndrome or history of Torsades de pointes (TdP). History of risk factors for TdP
• Treatment with strong CYP3A4 inhibitors within 1 week prior to the first dose of study drug or strong CYP3A4 inducers within 3 weeks prior to the first dose of study drug.

Phase I Dose-Expansion - and Phase II specific exclusion criteria:

• Presence of known EGFR, KRAS, ALK, HER2, ROS1, BRAF and METex14 activating mutations.