A Phase 1 Study of NOV1601(CHC2014) in Adult Subjects With Solid Organ Malignancies

Study Overview
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Brief Summary
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This study is a first-in-human (FIH) study which is required to understand the PK characteristics, MTD, and safety profile of NOV1601(CHC2014) in subjects with solid organ malignancies.

Detailed Description
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This is the first-in-human, Phase 1, open-label, multicenter, dose-escalation study to investigate the safety, tolerability, PK, and clinical activity of NOV1601(CHC2014) in subjects with solid organ malignancies. The primary goal of the study is to determine the RP2D of NOV1601(CHC2014) in adult subjects with solid organ malignancies. Dose escalation will follow a 3+3 design and will be based on prior cohort review. There will be 2 branches of the dosing schedule, once a day(QD) and twice daily(BID).

Official Title
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A Phase 1, Open-label, Dose-escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of NOV1601(CHC2014) in Adult Subjects With Solid Organ Malignancies

Conditions
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Phase 1, Solid Tumor, Adult

Intervention / Treatment
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* Drug: NOV1601(CHC2014)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria(partial): Pathological confirmation of malignancy and evidence of metastatic or surgically unresectable disease At least one evaluable or measurable lesion should be present and identified according to Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1 or Response Assessment in Neuro-Oncology(RANO) Relapse after or refractory to systemic drug therapy to malignancy, at least one regimen of cytotoxic chemotherapy, kinase inhibitors including tyrosine kinase inhibitors or immunotherapy which is considered as standard of care if there is no standard regimen recommended, then no experience of systemic drug therapy is acceptable Patients with primary central nervous system(CNS) tumors or metastasis, if they have been neurologically stable Symptoms should be under control by stable dose of glucocorticoids and analgesic drugs for symptom control at least 2 weeks prior to starting the treatment Stable dose of glucocorticoids and analgesic drugs for symptom control should be maintained throughout the study Subjects should be off from radiotherapy for at least 14 days prior to the start of study treatment(C1D1) without symptom aggravation Exclusion Criteria(partial): Prior high-dose chemotherapy requiring hematopoietic stem cell transplantation History or evidence of suspicious leptomeningeal disease Previous surgery of gastrectomy, gastrostomy or any medical condition which interferes with oral ingestion of capsule Indwelling percutaneous drainage of bile and chest tube Evidence of or suspicious symptomatic spinal cord compression, unless appropriately treated and neurologically stable off glucocorticoid for at least 2 weeks

Ages Eligible for Study
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Minimum Age: 19 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: NOV1601(CHC2014)<br>a highly selective pan-TRK(tropomyosin receptor kinase) inhibitor targeting tropomyosin receptor kinase A(TRKA), tropomyosin receptor kinase B(TRKB), and tropomyosin receptor kinase C(TRKC) | Drug: NOV1601(CHC2014)<br>* a highly selective pan-TRK(tropomyosin receptor kinase) inhibitor targeting tropomyosin receptor kinase A (TRKA), tropomyosin receptor kinase B(TRKB), and tropomyosin receptor kinase C(TRKC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the recommended Phase 2 dose(RP2D) or the maximum tolerated dose(MTD) of NOV1601 | MTD will be the RP2D, based on the pharmacokinetic(PK) profiles and safety profiles as assessed by the Safety Monitoring Committee (SMC). | Subjects will be treated and observed for dose-limiting toxicity(DLT) through the end of the first cycle (Days 1-28). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events(TEAE) and serious adverse events(SAE) | Each adverse event will be coded using the Medical Dictionary for Regulatory Activities(version 20.0) classification system. The severity of the toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. | Maximum 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tropomyosin receptor kinase, Solid organ malignancies