NCT06260514RecruitingPhase 1
A Phase 1, Open-Label, Multicenter, First-In-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of APR-1051 in Patients With Advanced Solid Tumors
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Aprea Therapeutics
- Enrollment
- 90
- Locations
- 6
- Primary Endpoint
- Treatment-related adverse events
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
APR-1051
Experimental
Dose Escalation based on BOIN Design
Intervention: APR-1051 (Drug)
Outcomes
Primary Outcomes
Treatment-related adverse events
Time Frame: 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
Time Frame: 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 Outcomes
- Pharmacokinetics: Tmax of APR-1051(Day 1 to 112)
- Pharmacokinetics: Cmax/Cmin of APR-1051(Day 1 to 112)
- Pharmacokinetics: AUC of APR-1051(Day 1 to 112)
- Pharmacokinetics: t1/2 of APR-1051(Day 1 to 112)
Investigators
Study Sites (6)
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Related News
Aprea Therapeutics Advances WEE1 and ATR Inhibitors in Clinical Trials- Aprea Therapeutics is progressing its Phase 1 ACESOT-1051 trial of APR-1051, a WEE1 inhibitor, showing promising tolerability in treating cancers with Cyclin E over-expression.
- The company's Phase 1/2a ABOYA-119 study is evaluating ATRN-119, an ATR inhibitor, for patients with DDR-related gene mutations, addressing a significant unmet medical need.
- Aprea Therapeutics reported $26.2 million in cash reserves, ensuring funding for at least the next twelve months, and appointed Dr. Philippe Pultar as a senior medical advisor.last yearAPR-1051 Shows Early Safety and Tolerability in Advanced Solid Tumors with Specific Gene Alterations- Preliminary data from the phase 1 ACESOT-1051 study indicates that APR-1051, an oral WEE1 inhibitor, is safe and well-tolerated in patients with advanced solid tumors.
- The study, involving three patients, showed no hematologic toxicity and only one possible treatment-related grade 1 adverse event at the assessed dose levels.
- APR-1051 has demonstrated anti-proliferative activity in cancer models, potentially offering an improved toxicity profile compared to other WEE1 inhibitors due to low off-target inhibition.
- The ACESOT-1051 trial is ongoing, evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of APR-1051 in patients with advanced solid tumors.last year