- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04383938
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a phase 1/2, open-label, study to determine the safety and preliminary efficacy of APR-246 (eprenetapopt) in combination with pembrolizumab in subjects with solid tumor malignancies. In the safety lead-in part of study (phase 1), the safety and the recommended phase 2 dose (RP2D) of APR-246 will be investigated.
In the expansion part of the study (phase 2), both safety and efficacy for the combination therapy will be investigated in the 3 cohorts.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Arizona
-
Phoenix, Arizona, United States, 85054
- Mayo Clinic
-
-
Florida
-
Jacksonville, Florida, United States, 32224
- Mayo Clinic
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, United States, 02115
- Dana Farber Cancer Center
-
-
Minnesota
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Rochester, Minnesota, United States, 55902
- Mayo Clinic
-
-
Missouri
-
Saint Louis, Missouri, United States, 63130
- Washington University
-
-
Tennessee
-
Nashville, Tennessee, United States, 37235
- Vanderbilt University
-
-
Texas
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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:
- At least 1 lesion of ≥10 mm in the longest diameter (LD) for a non-lymph node or ≥15 mm in the short-axis diameter for a lymph node that is serially measurable according to RECIST 1.1.
- Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation must show subsequent evidence of substantial size increase (ex. 20% increase in LD) to be deemed a target lesion.
- Negative serum or urine pregnancy test prior to study treatment initiation in female subjects of childbearing potential.
- Women of childbearing potential and men with female partners of childbearing potential must be willing to use an effective form of contraception
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Safety Lead In
Patients with advanced solid tumors.
Up to 3 dose levels evaluated.
|
APR-246 D1-4 + Pembrolizumab D3
|
Experimental: Expansion 1
Patients with advanced gastric cancer.
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APR-246 D1-4 + Pembrolizumab D3
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Experimental: Expansion 2
Patients with advanced urothelial/bladder cancer.
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APR-246 D1-4 + Pembrolizumab D3
|
Experimental: Expansion 3
Patients with advanced NSCLC.
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APR-246 D1-4 + Pembrolizumab D3
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To evaluate the safety and tolerability of APR-246 in combination with pembrolizumab in subjects with solid tumors.
Time Frame: Through study completion, approximately 1 year
|
To determine the occurrence of dose limiting toxicities (DLTs), classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events 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 maximum tolerated dose (MTD) for APR-246 in combination with pembrolizumab
Time Frame: Through safety lead in period, approximately 6 months
|
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, approximately 6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Joachim Gullbo, MD, Theradex Oncology
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- A20-11195
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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