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 biopsy or liquid biopsy. Ifdeemed appropriate by the investigator, determination on a pleural cell block isalso 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 RETselective inhibitors and no prior systemic anti-cancer treatment. Patients whohave been treated with neo-adjuvant or adjuvant chemotherapy may be included ifit 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 fusionand 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 andanticonvulsant for at least 7 days or

• asymptomatic brain metastases already treated with local therapy and beclinically stable on steroids and anticonvulsant for at least 7 days beforestudy 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 selectiveinhibitors;

• NSCLC patients with RET gene fusion and without prior exposure to RET selectiveinhibitors

• patients with advanced solid tumors that harbour RET gene abnormalities (otherthan NSCLC patients with primary RET gene fusions) and has failed all theavailable 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 andanticonvulsant for at least 7 days or

• asymptomatic brain metastases already treated with local therapy and beclinically stable on steroids and anticonvulsant for at least 7 days beforestudy 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 firstdose of study drug

• Major surgery (excluding placement of vascular access) within 4 weeks prior to thefirst dose of study drug or planned major surgery during the course of studytreatment.

• Whole Brain Radiotherapy within 14 days or other palliative radiotherapy within 7days prior to the first dose of study drug, or persisting side effects of suchtherapy, in the opinion of the Investigator.

• Clinically significant, uncontrolled, cardiovascular disease including myocardialinfarction 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) classIII-IV, and severe uncontrolled arterial hypertension, according to theInvestigator's opinion.

• QT interval corrected using Fridericia's formula (QTcF) >470 msec; personal orfamily 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 ofstudy drug or strong CYP3A4 inducers within 3 weeks prior to the first dose of studydrug.

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

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