HEC169096 in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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An Open, Multi-Center Phase I/II Clinical Study To Evaluate The Safety, Tolerability, Pharmacokinetic Characteristics And Effectiveness Of HEC169096 In Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors.

Detailed Description
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This is an open-label, multi-center Phase 1/2 study in participants with advanced solid tumors, including RET fusion-positive NSCLC, MTC, and other tumors with RET activation. Phase I of this study includes a dose-escalation phase and a dose-expansion phase , which will focus on exploring MTD and/or RP2D of HEC169096 in patients with advanced solid tumours; Phase II will assess the efficacy and safety of HEC169096 at the RP2D dose.

Official Title
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Phase 1/2 Study of the Highly-selective RET Inhibitor,HEC169096 in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: HEC169096


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase 1：Pathologically documented, definitively diagnosed non-resectable advanced solid tumor. Phase 2： All participants must have an oncogenic RET-rearrangement/fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor. Participants has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. Measurable or non-measurable disease as determined by RECIST 1.1; Adequate hematologic, hepatic and renal function; Life expectancy of at least 12 weeks; Negative pregnancy test (urine or serum) for female patients of childbearing potential; Participants agrees to provide tumor tissue (archived, if available or a fresh biopsy). Exclusion Criteria: Participant's cancer has a known primary driver alteration other than RET. Nitrosourea, anthracyclines and mitomycin chemotherapy within 6 weeks prior to study treatment; Chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks or 5 half-lives (whichever is longer) prior to study treatment; Those who have received more than 30% of bone marrow radiation or wide-range radiotherapy within 4 weeks before the first study drug treatment (the patients receiving palliative radiotherapy are within 2 weeks before receiving study drug treatment); Had received traditional Chinese medicine for anti-tumor within a week before receiving study drug treatment; Had received live vaccine within 4 weeks prior to study treatment; Had received any investigational agent from other clinical study within 4 weeks or 5 half-lives (whichever is longer) prior to study treatment or are currently participating in other clinical trials; Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment . Central nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms. Patients with other malignant tumors within 5 years before the first use of drugs Patients have a history of severe cardiovascular disease; Active hepatitis (Hepatitis B: HBsAg-positive and HBV-DNA ≥ 2000 IU/ mL or ≥ 10^4 cps/ mL; Hepatitis B: HCV antibody-positive and HCV-RNA positive), HIV antibody-positive. Patients with clinically active interstitial lung disease, active pneumonia, and radiation pneumonia requiring treatment; Poorly controlled pleural effusion, abdominal effusion, or pericardial effusion after intervention (such as drainage); Clinically significant active malabsorption syndrome or other diseases that may affect study drug administration and gastrointestinal absorption; Patients have been treated with any strong CYP3A inhibitors or inducers within 2 weeks prior to the first dose or PPIs in the first week before the first dose.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEC169096<br>Multiple doses of HEC169096 | Drug: HEC169096<br>* Multiple doses of HEC169096 during Phase 2；Oral dose of HEC169096 as determined during Phase 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: MTD and RP2D of HEC169096 | Determination of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of HEC169096 | Cycle 1 (28 days) of treatment for MTD and at the end of every 2 cycle for RP2D for approximately 12 months or earlier if participant terminates from the study | 
| Phase 2: Overall Response Rate | As assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) | through study completion, an average of 1 year |