Clinical Trials /

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

NCT04683250

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities
  • Official Title: Phase I/II Study of the Selective RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities

Clinical Trial IDs

  • ORG STUDY ID: HM06-19-26
  • NCT ID: NCT04683250

Conditions

  • RET-altered Non Small Cell Lung Cancer
  • RET-altered Solid Tumors

Interventions

DrugSynonymsArms
TAS0953/HM06TAS0953/HM06 Phase 1
TAS0953/HM06TAS0953/HM06 Phase 2

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.

Trial Arms

NameTypeDescriptionInterventions
TAS0953/HM06 Phase 1ExperimentalDose escalation and dose expansion until recommended Phase 2 dose determined
  • TAS0953/HM06
TAS0953/HM06 Phase 2ExperimentalTreatment phase at recommended Phase 2 dose in three different populations
  • TAS0953/HM06

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1 (dose-escalation): Maximum Tolerated Dose (MTD)
Time Frame:At the end of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:Incidence rate and category of dose limiting toxicities (DLTs)

Secondary Outcome Measures

Measure:Phase 1 (dose expansion): Objective Response Rate (ORR) by IDMC
Time Frame:Approximately every 6 weeks for 6 months, then every 9 weeks during treatment, 7 days after the last dose, and every 3 months after the last dose (up to an average of 2 years) in patients without progressive disease
Safety Issue:
Description:Proportion of patients with confirmed complete response (CR) and or partial response (PR) according to RECIST 1.1 as assessed by IDMC
Measure:Phase 2: ORR by Investigator
Time Frame:Approximately every 6 weeks for 6 months, then every 9 weeks during treatment, 7 days after the last dose, and every 3 months after the last dose (up to an average of 2 years) in patients without progressive disease
Safety Issue:
Description:Proportion of patients with confirmed complete response (CR) and or partial response (PR) according to RECIST 1.1 as assessed by Investigator
Measure:Phase 2: Disease Control Rate (DCR)
Time Frame:Approximately every 6 weeks for 6 months, then every 9 weeks during treatment, 7 days after the last dose, and every 3 months after the last dose (up to an average of 2 years) in patients without progressive disease
Safety Issue:
Description:Proportion of patients with confirmed complete response (CR), partial response (PR) and Stable Disease according to RECIST 1.1 as assessed by Investigator
Measure:Phase 2: Time to Tumor Response (TTR)
Time Frame:From date of randomization until the date of first documentation of objective tumor response, assessed up to an average of 2 years.
Safety Issue:
Description:Time from first dose to first documentation of objective tumor response (CR or PR)
Measure:Phase 2: Progression Free Survival (PFS)
Time Frame:From date of randomization until the date of first documented progression or death due to any cause, whichever occurs first, assessed up to an average of 2 years.
Safety Issue:
Description:Time from first dose to first documentation of objective disease progression or to death due to any cause, whichever occurs first
Measure:Phase 2: Time to Progression (TTP)
Time Frame:From date of randomization until the date of first documented progression, assessed up to an average of 2 years
Safety Issue:
Description:Time from first dose to objective tumor progression
Measure:Phase 2: Duration of Response (DOR)
Time Frame:From first documentation of objective tumor response (CR or PR) until the date of first documented progression or death due to any causes, whichever occurs first, assessed up to an average of 2 years
Safety Issue:
Description:Time from first documentation of tumor response (CR + PR) to disease progression or death due any cause whichever occurs first
Measure:Phase 2: Overall Survival (OS)
Time Frame:From date of randomization until the date of death due to any cause, assessed up to an average of 2 years
Safety Issue:
Description:Time from first dose to date of death due to any cause
Measure:Phase 2: Central Nervous System (CNS) ORR (C-ORR)
Time Frame:Approximately every 6 weeks for 6 months, then every 9 weeks during treatment, 7 days after the last dose, and every 3 months after the last dose (up to an average of 2 years) in patients without progressive disease
Safety Issue:
Description:Rate of confirmed CR and PR relative to patients with brain lesions at study entry
Measure:Phase 2: Central Nervous System DOR (C-DOR)
Time Frame:From first documentation of objective tumor response (CR or PR) until the date of first documented progression or death due to any causes, whichever occurs first, assessed up to an average of 2 years
Safety Issue:
Description:Time from documentation of intracranial tumor response to disease progression or death due to any cause whichever occurs first
Measure:Phase 2: Time to CNS progression
Time Frame:From date of randomization until the date of first documented progression, assessed up to an average of 2 years
Safety Issue:
Description:Time from the first dose to the first radiological evidence of CNS disease progression
Measure:Phase 1 (dose-escalation): Area under the plasma concentration versus time curve from time 0 to 12 hours (AUC0-12)
Time Frame:Day -1 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): AUC0-24
Time Frame:Day -1 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): AUC0-infinity
Time Frame:Day -1 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): AUC0-12 at steady state
Time Frame:Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Maximum drug concentration (Cmax)
Time Frame:Day -1 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Trough drug concentration at 12 hours (Ctrough)
Time Frame:Day -1 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Time to maximum plasma concentration (tmax)
Time Frame:Day -1 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Terminal half-life (t1/2)
Time Frame:Day -1 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Accumulation factor based on Cmax (Rmax)
Time Frame:Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Accumulation factor based on Ctrough (Rmin)
Time Frame:Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Terminal rate constant (lambda_z)
Time Frame:Day -1 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Volume of Distribution (Vz/F)
Time Frame:Day -1 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Systemic clearance (CL/F)
Time Frame:Day -1 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Amount excreted in 0-24 hour urine (Ae0-24)
Time Frame:Day -1 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-escalation): Renal Clearance (CL_R)
Time Frame:Day -1 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-expansion): AUC0-12 at steady state
Time Frame:Day 8 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-expansion): Maximum drug concentration (Cmax)
Time Frame:Day 8 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-expansion): Trough drug concentration at 12 hours (Ctrough)
Time Frame:Day 8 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-expansion): Time to maximum plasma concentration (tmax)
Time Frame:Day 8 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-expansion): Terminal rate constant (lambda_z)
Time Frame:Day 8 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1 (dose-expansion): Terminal half-life (t1/2)
Time Frame:Day 8 and Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 2 Population PK: Typical value of absorption rate constant (Ka)
Time Frame:Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 2 Population PK: Typical value of CL/F
Time Frame:Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 2 Population PK: Typical value of volume of distribution (V/F)
Time Frame:Day 15 of Cycle 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Phase 1: Incidence of abnormal electrocardiograms (ECG QT interval). QT will be corrected for heart rate (QTc) using Fridericia's formula (QTcF).
Time Frame:On Day 1, Day 8 (only in dose escalation), Day 15 in cycle 1, Day 1 of any subsequent cycles (each cycle is 21 days) during treatment, for approximately 10 months (or earlier if the patient discontinues from the study), and 7 days after last dose
Safety Issue:
Description:
Measure:Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
Time Frame:From the time of informed consent, for approximately 10 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Safety Issue:
Description:
Measure:Phase 1: Incidence of serious adverse events (SAEs)
Time Frame:From the time of informed consent, for approximately 10 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Safety Issue:
Description:
Measure:Phase 2: Incidence of abnormal electrocardiograms (ECG QT interval). QT will be corrected for heart rate (QTc) using Fridericia's formula (QTcF).
Time Frame:On Day 1 and Day 15 in cycle 1, Day 1 of any subsequent cycles (each cycle is 21 days) during treatment, for approximately 2 years (or earlier if the patient discontinues from the study), and 7 days after last dose
Safety Issue:
Description:
Measure:Phase 2: Incidence of treatment-emergent adverse events (TEAEs)
Time Frame:From the time of informed consent for approximately 2 years (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Safety Issue:
Description:
Measure:Phase 2: Incidence of serious adverse events (SAEs)
Time Frame:From the time of informed consent for approximately 2 years (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Helsinn Healthcare SA

Last Updated

December 24, 2020