Study of APR-1051 in Patients With Advanced Solid Tumors

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

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 Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: APR-1051

• Study Type: Interventional
• Enrollment (Estimated): 79
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Crystal L Miller, RN BSN; Phone Number: 1-617-463-9385; Email: crystal.miller@aprea.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APR-1051; 3+3 Dose Escalation Design	Drug: APR-1051; WEE1 Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related adverse events	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	Day 1 to 28, each cycle is 28 days
Recommended dose of APR-1051	•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	Day 1 to 28, each cycle is 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Cmax/Cmin of APR-1051	Plasma concentration of APR-1051: maximum (Cmax), minimum (Cmin)	Day 1 to 112
Pharmacokinetics: Tmax of APR-1051	Time to peak plasma concentration of APR-1051 (Tmax)	Day 1 to 112
Pharmacokinetics: AUC of APR-1051	Area under plasma versus time curve (AUC) of APR-1051 max)	Day 1 to 112
Pharmacokinetics: t1/2 of APR-1051	Half-life of APR-1051 (t1/2)	Day 1 to 112

Collaborators and Investigators

• Sponsor: Aprea Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: January 18, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Estimated): February 15, 2024

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: APR-1051-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No