Recruiting
Phase 1/2
Study of RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities
Condition(s) studied
RET-altered Non Small Cell Lung CancerRET-altered Solid Tumors
Investigational drug(s) / intervention(s)
TAS0953/HM06TAS0953/HM06
TAS0953/HM06: Phase 1: oral, starting dose 20mg twice a day, until recommended phase 2 dose, continuous daily dosing, cycles lasting 21 days
TAS0953/HM06: Phase 2: oral, recommended dose twice a day, continuous daily dosing, cycles lasting 21 days
Study 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.
Eligibility
Ages Eligible for Study:
\- Adult patient (The definition of adulthood shall comply with the regulatory requirements of each region)
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. If deemed appropriate by the investigator, determination on a pleural cell block or cell pellet is also 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 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
* 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.
Primary outcome measure(s)
- Phase 1 (dose-escalation): Maximum Tolerated Dose (MTD) — At the end of Cycle 1 (each cycle is 21 days)
Incidence rate and category of dose limiting toxicities (DLTs)
- 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 — 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.
Proportion of patients with confirmed complete response (CR) and or partial response (PR) according to RECIST 1.1 as assessed by independent central review
Trial sites (29)
| Facility | City | Region | Status |
| Chao Family Comprehensive Cancer Center |
Orange |
California |
Terminated |
| Stanford Cancer Center |
Stanford |
California |
Terminated |
| Massachusetts General Hospital |
Boston |
Massachusetts |
Terminated |
| Henry Ford Hospital |
Detroit |
Michigan |
Terminated |
| START Midwest - Cancer & Hematology Centers of Western Michigan |
Grand Rapids |
Michigan |
Terminated |
| Laura and Isaac Perlmutter Cancer Center at NYU Langone Health |
New York |
New York |
Terminated |
| Memorial Sloan Kettering Cancer Center |
New York |
New York |
Terminated |
| The Sarah Cannon Research Institute/Tennessee Oncology |
Nashville |
Tennessee |
Terminated |
| The University of Texas M. D. Anderson Cancer Center |
Houston |
Texas |
Terminated |
| Cabrini Hospital |
Malvern |
Australia |
Recruiting |
| Linear Clinical Research |
Nedlands |
Australia |
Recruiting |
| GenesisCare North Shore |
Saint Leonards |
Australia |
Recruiting |
| National Cancer Center Hospital East |
Kashiwa-shi |
Chiba |
Recruiting |
| Tohoku University Hospital |
Sendai |
Miyagi |
Recruiting |
| Okayama University Hospital |
Okayama |
Okayama-ken |
Recruiting |
| Kansai Medical University Hospital |
Hirakata-shi |
Osaka |
Recruiting |
| Osaka International Cancer Institute |
Osaka |
Osaka |
Recruiting |
| Shizuoka Cancer Center |
Shizuoka |
Shizuoka |
Recruiting |
| National Cancer Center Hospital |
Chuo-ku |
Tokyo |
Recruiting |
| The Cancer Institute Hospital of JFCR |
Koto-ku |
Tokyo |
Recruiting |
| Aichi Cancer Center |
Aichi |
Japan |
Recruiting |
| National Hospital Organization Kyushu Cancer Center |
Fukuoka |
Japan |
Recruiting |
| Kanagawa Cancer Center |
Kanagawa |
Japan |
Recruiting |
| Kurashiki Central Hospital |
Okayama |
Japan |
Recruiting |
| Kindai University Hospital |
Osaka |
Japan |
Recruiting |
| Seoul National University Bundang Hospital |
Seongnam |
South Korea |
Recruiting |
| Samsung Medical Center |
Seoul |
South Korea |
Recruiting |
| Seoul National University Hospital |
Seoul |
South Korea |
Recruiting |
| Severance Hospital |
Seoul |
South Korea |
Recruiting |
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