Purpose

Phase 1 and 2 trial to study the safety, pharmacokinetics, and efficacy of TAS0953/HM06 in patients with advanced solid tumors with RET gene abnormalities. Phase 1 aims to determine the Maximum Tolerated Dose (MTD) and identify the Recommended Phase 2 Dose (RP2D) to be used in phase 2.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Dose escalation phase followed by a dose expansion phase (Phase 1), then followed by a Phase 2 at the recommended dose
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
TAS0953/HM06 Phase 1
Dose escalation and dose expansion until recommended Phase 2 dose determined
  • Drug: TAS0953/HM06
    Phase 1: oral, starting dose 20mg twice a day, until recommended phase 2 dose, continuous daily dosing, cycles lasting 21 days
Experimental
TAS0953/HM06 Phase 2
Treatment phase at recommended Phase 2 dose in three different populations
  • Drug: TAS0953/HM06
    Phase 2: oral, recommended dose twice a day, continuous daily dosing, cycles lasting 21 days

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Justin Gainor, MD
617-724-4000

More Details

Status
Recruiting
Sponsor
Helsinn Healthcare SA

Study Contact

Michael Karl
+49 8709 943 761
Michael.Karl@iconplc.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.