A Phase I/II Study to Evaluate the Safety, Pharmacokinetics and Efficacy of PRJ1-3024 in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a multicenter, open-label study to assess the safety and preliminary efficacy and to determine the maximum tolerated dose (MTD) or maximum administration dose (MAD) and recommended Phase 2 doses (RP2D) of PRJ1-3024 in subjects with relapsed/refractory solid tumors. The study consists of two parts, one is a 3+3 dose escalation study and another is a pharmaceutical extension of RP2D.

Detailed Description
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Using dose escalation, the study will evaluate the safety, tolerability, PK, and pharmacodynamics of PRJ1-3024 and will determine the maximum tolerated dose in subjects with advanced solid tumors. Participants with advanced solid tumor will receive PRJ1-3024 daily as an oral therapy and test the impact of of PRJ1-3024 on tumors. This study will find the safe and tolerable recommended dose in subjects with advanced solid tumors in a open-label, 3+3 dose escalation study and use the RP2D to assess the preliminary efficacy of PRJ1-3024 in a long-term extension study.

Official Title
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A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Prime Efficacy of PRJ1-3024 in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor, Advanced Solid Malignancies

Intervention / Treatment
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* Drug: PRJ1-3024


Participation Criteria
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Eligibility Criteria
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- Key Inclusion Criteria: Histologically or cytologically confirmed locally advanced (unresectable) or metastatic r/r solid tumors for which no standard therapy is available or for whom standard therapy is considered unsuitable or intolerable. Male or non-pregnant, non-lactating female subjects age ≥18 years. ECOG Performance Status 0 1. Has at least 1 measurable lesion as defined by RECIST 1.1 criteria . Life expectancy of >3 months, in the opinion of the Investigator. Able to take oral medications and willing to record daily adherence to investigational product. Adequate hematologic parameters unless clearly due to the disease under study. Adequate renal and hepatic function Able to understand and willing to sign a written informed consent form. Key Exclusion Criteria: History of another malignancy Known symptomatic brain metastases requiring >10 mg/day of prednisolone. Significant cardiovascular disease. Known active HBV, HCV, AIDS-related illness. Has received a live vaccine within 30 days. History of active autoimmune disorders, or ongoing immunosuppressive therapy or ongoing . Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to < Grade 2. Receiving concurrent anti-cancer therapy, investigational product, strong inhibitors or inducers of cytochrome P450 3A (CYP3A) . Prior treatment with hematopoietic progenitor kinase 1 (HPK1) inhibitors.

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1 is a Phase 1, open label, 3+3 dose escalation study to determine the safety and preliminary efficacy of PRJ1-3024. Upon completing Phase 1 and depending on data obtained, dose expansion may proceed in Phase 2 to confirm the tolerability and efficacy of the RP2D of PRJ1-3024 .
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy Escalation<br>3+3 Dose escalation arm with PRJ1-3024 which will begin with 2 subjects treated at the lowest planned dose level. PRJ1-3024 is administered orally once daily. The starting dose is 80mg/day. | Drug: PRJ1-3024<br>* PRJ1-3024 is provided as capsules and is administered orally once a day.<br>|
| Experimental: Monotherapy Exploration of the recommended dose<br>Upon completing Phase 1 and depending on data obtained, dose expansion may proceed in Phase 2 with several cohorts enrolled to confirm the tolerability of the RP2D of PRJ1-3024 (determined in Phase 1). PRJ1-3024 is administered orally once daily. The starting dose is determined by clinical effecacy data from Phase 1, and treatment may continue for up to 2 years as long as the subject experiences clinical benefit in the opinion of the Investigator and shows no signs or symptoms of unequivocal progression of disease. | Drug: PRJ1-3024<br>* PRJ1-3024 is provided as capsules and is administered orally once a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity (DLT) events during the DLT monitoring period | Safety listings and pharmacokinetic listings will be used for evaluation | Day 1 to Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | Characterized by type, seriousness, relationship to study treatment, timing, and severity. | 24 months | 
| Pharmacokinetic parameter# Accumulation ratio | to estimate the accumulation of PRJ1-3024 from time 0 to the time of last quantifiable concentration after multiple administration | 24 months | 
| Objective response rate (ORR) | estimated by the proportion of subjects having a complete response (CR) or partial response (PR) with use of RECIST v1.1 criteria. | 24 months | 
| Duration of response (DOR) | defined as time from the first occurrence of a documented objective response to the time of relapse or death from any cause. | 24 months | 
| Pharmacokinetic parameter#AUC0-last# | Area under the concentration-time curve AUC from time 0 to the time of the last quantifiable concentration | 24 months | 
| Pharmacokinetic parameter#Maximum observed concentration (Cmax) | assessed as time from time 0 to the time of the last quantifiable concentration | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Maximum tolerated dose, Recommended Phase 2 dose, Dose Escalation, Hematopoietic progenitor kinase 1, PRJ1-3024