A Phase I/II Study to Evaluate the Safety, Pharmacokinetics and Efficacy of PRJ1-3024 in Subjects With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Monotherapy Escalation 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
PRJ1-3024 is provided as capsules and is administered orally once a day.
|
| Experimental: Monotherapy Exploration of the recommended dose 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
PRJ1-3024 is provided as capsules and is administered orally once a day.
|
Outcome Measures
Primary Outcome Measures
- Incidence of dose-limiting toxicity (DLT) events during the DLT monitoring period [Day 1 to Day 21]
Safety listings and pharmacokinetic listings will be used for evaluation
Secondary Outcome Measures
- Incidence of adverse events (AEs) [24 months]
Characterized by type, seriousness, relationship to study treatment, timing, and severity.
- Pharmacokinetic parameter# Accumulation ratio [24 months]
to estimate the accumulation of PRJ1-3024 from time 0 to the time of last quantifiable concentration after multiple administration
- Objective response rate (ORR) [24 months]
estimated by the proportion of subjects having a complete response (CR) or partial response (PR) with use of RECIST v1.1 criteria.
- Duration of response (DOR) [24 months]
defined as time from the first occurrence of a documented objective response to the time of relapse or death from any cause.
- Pharmacokinetic parameter#AUC0-last# [24 months]
Area under the concentration-time curve AUC from time 0 to the time of the last quantifiable concentration
- Pharmacokinetic parameter#Maximum observed concentration (Cmax) [24 months]
assessed as time from time 0 to the time of the last quantifiable concentration
Eligibility Criteria
Criteria
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Key Inclusion Criteria:
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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.
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Male or non-pregnant, non-lactating female subjects age ≥18 years.
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ECOG Performance Status 0~1.
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Has at least 1 measurable lesion as defined by RECIST 1.1 criteria .
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Life expectancy of >3 months, in the opinion of the Investigator.
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Able to take oral medications and willing to record daily adherence to investigational product.
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Adequate hematologic parameters unless clearly due to the disease under study.
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Adequate renal and hepatic function
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Able to understand and willing to sign a written informed consent form.
Key Exclusion Criteria:
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History of another malignancy
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Known symptomatic brain metastases requiring >10 mg/day of prednisolone.
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Significant cardiovascular disease.
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Known active HBV, HCV, AIDS-related illness.
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Has received a live vaccine within 30 days.
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History of active autoimmune disorders, or ongoing immunosuppressive therapy or ongoing .
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Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to < Grade 2.
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Receiving concurrent anti-cancer therapy, investigational product, strong inhibitors or inducers of cytochrome P450 3A (CYP3A) .
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Prior treatment with hematopoietic progenitor kinase 1 (HPK1) inhibitors.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The first affiliated hospital of Zhengzhou University | Zhengzhou | Henan | China | |
| 2 | West China Hospital of Sichuan University | Chengdu | Sichuan | China | |
| 3 | Cancer hospital of the University of Chinese Academy of Sciences | Hangzhou | Zhejiang | China | |
| 4 | Beijing Cancer Hospital | Beijing | China | 100142 | |
| 5 | The Fifth Medical Center of PLA General Hospital | Beijing | China |
Sponsors and Collaborators
- Zhuhai Yufan Biotechnologies Co., Ltd
Investigators
- Study Director: Hui ouyang, Dr., VP
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRJ1-3024-001
- CXHL2101725