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

NCT04683250 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HM06-19-26
• Study Type: interventional
• Target: 244
• Locations: 3 countries
• Sites: 21

Brief Summary

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

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

Outcome Measures

Primary Outcomes (3)

• Phase 1 (dose-escalation): Maximum Tolerated Dose (MTD)

  Incidence rate and category of dose limiting toxicities (DLTs)

  At the end of Cycle 1 (each cycle is 21 days)

• Phase 1 (dose-expansion): Recommended Phase 2 dose (RP2D)

  At the end of Cycle 1 (each cycle is 21 days), and at the end of every subsequent cycle (each cycle is 21 days) for approximately 10 months (or earlier if patient discontinues the study)

• Phase 2: Objective Response Rate (ORR) by independent central review

  Proportion of patients with confirmed complete response (CR) and or partial response (PR) according to RECIST 1.1 as assessed by independent central review

  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.

Secondary Outcomes (41)

• Phase 1 (dose expansion): Objective Response Rate (ORR) by independent central review

  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

• Phase 2: ORR by Investigator

  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

• Phase 2: Disease Control Rate (DCR)

  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

• Phase 2: Time to Tumor Response (TTR)

  From date of randomization until the date of first documentation of objective tumor response, assessed up to an average of 2 years.

• Phase 2: Progression Free Survival (PFS)

  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.

Study Arms (2)

TAS0953/HM06 Phase 1

EXPERIMENTAL

Dose escalation and dose expansion until recommended Phase 2 dose determined

Drug: TAS0953/HM06

TAS0953/HM06 Phase 2

EXPERIMENTAL

Treatment phase at recommended Phase 2 dose in three different populations

Drug: TAS0953/HM06

Interventions

TAS0953/HM06 DRUG

Phase 1: oral, starting dose 20mg twice a day, until recommended phase 2 dose, continuous daily dosing, cycles lasting 21 days

TAS0953/HM06 Phase 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• 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

You may not qualify if:

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

Sponsors & Collaborators

• Taiho Pharmaceutical Co., Ltd.: lead
• Linical Co., Ltd.: collaborator

Study Sites (21)

Chao Family Comprehensive Cancer Center

Orange, California, 92868-3298, United States

TERMINATED

Stanford Cancer Center

Stanford, California, 94305-5826, United States

TERMINATED

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

TERMINATED

Henry Ford Hospital

Detroit, Michigan, 48202, United States

TERMINATED

START Midwest - Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49546, United States

TERMINATED

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

TERMINATED

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

TERMINATED

The Sarah Cannon Research Institute/Tennessee Oncology

Nashville, Tennessee, 37203, United States

TERMINATED

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030-4009, United States

TERMINATED

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

RECRUITING

Tohoku University Hospital

Sendai, Miyagi, Japan

RECRUITING

Okayama University Hospital

Okayama, Okayama-ken, Japan

RECRUITING

Kansai Medical University Hospital

Hirakata-shi, Osaka, Japan

RECRUITING

Osaka International Cancer Institute

Osaka, Osaka, Japan

RECRUITING

Shizuoka Cancer Center

Shizuoka, Shizuoka, Japan

RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

RECRUITING

National Hospital Organization Kyushu Cancer Center

Fukuoka, Japan

RECRUITING

Kanagawa Cancer Center

Kanagawa, Japan

RECRUITING

Kurashiki Central Hospital

Okayama, Japan

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Central Study Contacts

Kazuo Koba

CONTACT

+08 8010113399; k-koba@taiho.co.jp

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation phase followed by a dose expansion phase (Phase 1), then followed by a Phase 2 at the recommended dose

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: December 24, 2020
• Study Start: December 16, 2020
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2031
• Last Updated: March 3, 2026

Record last verified: 2026-02

Locations

US (9); JP (11); KR (1)