Clinical trial NCT05315167: A Phase I/II Study to Evaluate the Safety, Pharmacokinetics and Efficacy of PRJ1-3024 in Subjects with Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Advanced Solid Malignancies
Keywords: Maximum tolerated dose
Recommended Phase 2 dose
Dose Escalation
Hematopoietic progenitor kinase 1
PRJ1-3024
Lead sponsor: Zhuhai Yufan Biotechnologies Co., Ltd
Sponsor class: INDUSTRY
First posted: 2022-04-07
Enrollment: 267
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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 .
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: - 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.

Primary outcomes:
measure: Incidence of dose-limiting toxicity (DLT) events during the DLT monitoring period
timeFrame: Day 1 to Day 21
Secondary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: 24 months
measure: Pharmacokinetic parameter# Accumulation ratio
timeFrame: 24 months
measure: Objective response rate (ORR)
timeFrame: 24 months
measure: Duration of response (DOR)
timeFrame: 24 months
measure: Pharmacokinetic parameter#AUC0-last#
timeFrame: 24 months
measure: Pharmacokinetic parameter#Maximum observed concentration (Cmax)
timeFrame: 24 months
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: The first affiliated hospital of Zhengzhou University
state: Henan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Cancer hospital of the University of Chinese Academy of Sciences
state: Zhejiang
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: The Fifth Medical Center of PLA General Hospital
Study officials:
affiliation: VP
name: Hui ouyang, Dr.
role: STUDY_DIRECTOR
References: