Advanced Solid Malignancies, Advanced Solid Tumor
Conditions
Keywords
Maximum tolerated dose, Recommended Phase 2 dose, Dose Escalation, Hematopoietic progenitor kinase 1, PRJ1-3024
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.
Interventions
DRUGPRJ1-3024
PRJ1-3024 is provided as capsules and is administered orally once a day.
Sponsors
Zhuhai Yufan Biotechnologies Co., Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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 .
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Incidence of adverse events (AEs) | 24 months | Characterized by type, seriousness, relationship to study treatment, timing, and severity. |
| 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 |
| 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. |
Countries
China
Contacts
Primary ContactLiting Lai
Outcome results
None listed