Phase 1/2 Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies
Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies
1 other identifier
interventional
40
1 country
8
Brief Summary
A phase 1/2, open-label, study to determine the safety and preliminary efficacy of APR-246 in combination with pembrolizumab in subjects with solid tumor malignancies. The study will include a safety lead-in portion followed by a phase 2 expansion portion in specific disease groups.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2020
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 7, 2020
CompletedFirst Posted
Study publicly available on registry
May 12, 2020
CompletedStudy Start
First participant enrolled
June 25, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2022
CompletedResults Posted
Study results publicly available
May 13, 2025
CompletedMay 13, 2025
May 1, 2025
1.8 years
May 7, 2020
February 27, 2024
May 12, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To Evaluate the Safety of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumors.
To determine the Frequency of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) related to APR-246 in combination with pembrolizumab.
Through study completion, approximately 1 year
To Confirm the Recommended Phase 2 Dose (RP2D) for APR-246 in Combination With Pembrolizumab
To determine the dose of APR-246 to be selected for the expansion phase based on the occurence of dose limiting toxicities (DLTs) experienced during the safety assessment period
Through safety lead in period, during cycle 1 (approximately 21 days)
Study Arms (4)
Safety Lead In-Phase 1 Dose Level 1
EXPERIMENTALAPR-246 4.5g/d with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced non-CNS primary tumors
Expansion 1- Gastric Cancer
EXPERIMENTALAPR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced gastric or GEJ tumors
Expansion 2- Bladder Cancer
EXPERIMENTALAPR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced bladder or urothelial tumors
Expansion 3 -NSCLC
EXPERIMENTALAPR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced NSCLC.
Interventions
APR-246 D1-4 + Pembrolizumab D3
Eligibility Criteria
You may qualify if:
- Signed informed consent form (ICF) and ability to comply with protocol requirements.
- Known tumor TP53 mutation status from recent or archival sample.
- Histologically and/or cytologically confirmed solid tumor malignancy
- Safety lead in- Advanced non-central nervous system (CNS) primary tumors that have progressed after first line treatment, who are intolerant to first line treatment, or who are unable to receive first line treatment, and for whom pembrolizumab, or pembrolizumab-based therapy is considered appropriate
- Expansion 1- Patients with a confirmed diagnosis of advanced gastric or gastroesophageal junction (GEJ) tumors that have progressed after first line treatment, who are intolerant to first line treatment, or who are unable to receive first line treatment
- Expansion 2- Patients with a confirmed diagnosis of advanced bladder/urothelial tumors that have progressed after first line treatment, or who are intolerant to first line treatment, or who are unable to receive first line treatment with cisplatin-based chemotherapy.
- Expansion 3- Confirmed diagnosis of advanced non-small cell lung cancer (NSCLC) previously treated with anti-PD-1 or anti-PD-L1 therapy.
- Adequate organ function
- Creatinine clearance \> 30 mL/min
- Total serum bilirubin \< 1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome, tumor involvement, hemolysis or considered an effect of regular blood transfusions
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 × ULN, unless due to involvement by the underlying malignancy.
- Projected life expectancy of ≥ 12 weeks.
- Age ≥ 18 years at the time of signing the ICF.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- In the expansion portion, measurable disease meeting the following criteria:
- +4 more criteria
You may not qualify if:
- Known history of untreated human immunodeficiency virus (HIV)/HIV with a detectable viral load or active hepatitis B or active hepatitis C infection.
- Cardiac abnormalities
- Concomitant malignancies or previous malignancies with less than a 1-year disease-free interval at the time of signing consent.
- Pregnancy or lactation.
- Active uncontrolled systemic infection.
- An autoimmune condition requiring ≥ 10 mg (or equivalent corticosteroid) prednisone daily, or any other systemic immunosuppressive treatment within 28 days of first dose of study therapy.
- Known history of active tuberculosis.
- Current (non-infectious) pneumonitis, or a history of pneumonitis that required steroids.
- A live vaccine administered within 30 days of the first dose of study treatment.
- Receipt of any investigational product within 14 days or 5 half-lives prior to study treatment initiation, whichever is shortest.
- Prior intolerance to pembrolizumab or other anti-PD-1/PD-L1 agents.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
Mayo Clinic
Phoenix, Arizona, 85054, United States
Mayo Clinic
Jacksonville, Florida, 32224, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Center
Boston, Massachusetts, 02115, United States
Mayo Clinic
Rochester, Minnesota, 55902, United States
Washington University
St Louis, Missouri, 63130, United States
Vanderbilt University
Nashville, Tennessee, 37235, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Park H, Shapiro GI, Gao X, Mahipal A, Starr J, Furqan M, Singh P, Ahrorov A, Gandhi L, Ghosh A, Hickman D, Gallacher PD, Wennborg A, Attar EC, Awad MM, Das S, Dumbrava EE. Phase Ib study of eprenetapopt (APR-246) in combination with pembrolizumab in patients with advanced or metastatic solid tumors. ESMO Open. 2022 Oct;7(5):100573. doi: 10.1016/j.esmoop.2022.100573. Epub 2022 Sep 7.
PMID: 36084396DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Medical Advisor
- Organization
- Aprea Therapeutics
Study Officials
- STUDY DIRECTOR
Joachim Gullbo, MD
Theradex Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 7, 2020
First Posted
May 12, 2020
Study Start
June 25, 2020
Primary Completion
April 30, 2022
Study Completion
April 30, 2022
Last Updated
May 13, 2025
Results First Posted
May 13, 2025
Record last verified: 2025-05