Advanced Solid Tumor
Conditions
Brief summary
The purpose of this study is to assess the safety and effectiveness of APR-1051 through the performance of a Phase 1, open-label, safety, PK, and preliminary efficacy study of oral APR-1051 in patients with advanced solid tumors.
Interventions
DRUGAPR-1051
WEE1 Inhibitor
Sponsors
Aprea Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Diagnosis of advanced/metastatic solid tumor * Measurable or evaluable disease per RECIST version 1.1 (radiographic disease progression per PCWG3 criteria for patients with mCRPC) * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 or Karnofsky Performance Status (KPS) ≥ 70% * Patients must have recovered to Grade 1 or baseline levels from toxicity or adverse events related to prior treatment for their cancer, excluding Grade ≤ 2 neuropathy, alopecia, or skin pigmentation * Adequate bone marrow and organ function * Women of child-bearing potential (WOCBP) or men of child-fathering potential must agree to use adequate contraception prior to study entry
Exclusion criteria
* Patient has had prior systemic anti-cancer therapy (cytotoxic chemotherapy, immunotherapy, targeted therapy) within 3 weeks (6 weeks in cases of mitomycin C, nitrosourea, lomustine) or at least 5 half-lives (whichever is shorter, but no less than 2 weeks) prior to Day 1 * Prior radiation therapy at the target lesion unless there is evidence of disease progression. If patient has had prior radiation therapy for disease progression, see Exclusion Criterion 1 for allowed interval between radiotherapy and Day 1 and recovery of AEs * Treatment with any investigational agent administered within 30 days or 5 half-lives, whichever is shorter, before the first dose of APR-1051 * Major surgery within 21 days prior to Day 1 * Concomitant treatment with other anti-cancer therapy, including chemotherapy, immunotherapy, biological therapy, radiation therapy (except palliative local radiation therapy), or other novel anti-cancer agents. Note: endocrine therapy for breast and prostate cancer is allowed along with agents to treat or prevent skeletal related events (zoledronic acid, pamidronate, denosumab) * Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related adverse events | Day 1 to 28, each cycle is 28 days | * Part 1 dose escalation: Incidence of adverse Events (AE), serious AEs (SAE), treatment-related AEs, AEs that would qualify as a dose-limiting toxicity (DLT), changes in clinical laboratory values, vital signs, ECG, ECHO * Part 1 dose escalation: Severity of adverse Events (AE), serious AEs (SAE), treatment-related AEs, and changes in clinical laboratory values, vital signs, ECG, ECHO according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 |
| Recommended dose of APR-1051 | Day 1 to 28, each cycle is 28 days | •Part 1 dose escalation: Recommended Phase 2 Dose (RP2D) of APR-1051 monotherapy \[Time frame: Day 1 through to start of dose expansion phase\]. The RP2D of will be determined based on review of safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Cmax/Cmin of APR-1051 | Day 1 to 112 | Plasma concentration of APR-1051: maximum (Cmax), minimum (Cmin) |
| Pharmacokinetics: Tmax of APR-1051 | Day 1 to 112 | Time to peak plasma concentration of APR-1051 (Tmax) |
| Pharmacokinetics: AUC of APR-1051 | Day 1 to 112 | Area under plasma versus time curve (AUC) of APR-1051 max) |
| Pharmacokinetics: t1/2 of APR-1051 | Day 1 to 112 | Half-life of APR-1051 (t1/2) |
Countries
United States
Contacts
CONTACTSenior Medical Advisor
Outcome results
None listed