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Phase 1/2 Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04383938
Recruitment Status : Completed
First Posted : May 12, 2020
Last Update Posted : June 3, 2022
Sponsor:
Information provided by (Responsible Party):
Aprea Therapeutics

Tracking Information
First Submitted Date  ICMJE May 7, 2020
First Posted Date  ICMJE May 12, 2020
Last Update Posted Date June 3, 2022
Actual Study Start Date  ICMJE June 25, 2020
Actual Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2020)
  • 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.
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1/2 Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies
Official Title  ICMJE Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Bladder Cancer
  • Gastric Cancer
  • Non Small Cell Lung Cancer
  • NSCLC
  • Urothelial Carcinoma
  • Advanced Solid Tumor
Intervention  ICMJE Drug: APR-246 (eprenetapopt) + Pembrolizumab
APR-246 D1-4 + Pembrolizumab D3
Study Arms  ICMJE
  • Experimental: Safety Lead In
    Patients with advanced solid tumors. Up to 3 dose levels evaluated.
    Intervention: Drug: APR-246 (eprenetapopt) + Pembrolizumab
  • Experimental: Expansion 1
    Patients with advanced gastric cancer.
    Intervention: Drug: APR-246 (eprenetapopt) + Pembrolizumab
  • Experimental: Expansion 2
    Patients with advanced urothelial/bladder cancer.
    Intervention: Drug: APR-246 (eprenetapopt) + Pembrolizumab
  • Experimental: Expansion 3
    Patients with advanced NSCLC.
    Intervention: Drug: APR-246 (eprenetapopt) + Pembrolizumab
Publications * 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 Sep 6;7(5):100573. doi: 10.1016/j.esmoop.2022.100573. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 18, 2022)
37
Original Estimated Enrollment  ICMJE
 (submitted: May 11, 2020)
118
Actual Study Completion Date  ICMJE April 30, 2022
Actual Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed informed consent form (ICF) and ability to comply with protocol requirements.
  2. Known tumor TP53 mutation status from recent or archival sample.
  3. Histologically and/or cytologically confirmed solid tumor malignancy

    1. 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
    2. 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
    3. 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.
    4. Expansion 3- Confirmed diagnosis of advanced non-small cell lung cancer (NSCLC) previously treated with anti-PD-1 or anti-PD-L1 therapy.
  4. Adequate organ function

    1. Creatinine clearance > 30 mL/min
    2. 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
    3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 × ULN, unless due to involvement by the underlying malignancy.
  5. Projected life expectancy of ≥ 12 weeks.
  6. Age ≥ 18 years at the time of signing the ICF.
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  8. In the expansion portion, measurable disease meeting the following criteria:

    1. 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.
    2. 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.
  9. Negative serum or urine pregnancy test prior to study treatment initiation in female subjects of childbearing potential.
  10. Women of childbearing potential and men with female partners of childbearing potential must be willing to use an effective form of contraception

Exclusion Criteria:

  1. Known history of untreated human immunodeficiency virus (HIV)/HIV with a detectable viral load or active hepatitis B or active hepatitis C infection.
  2. Cardiac abnormalities
  3. Concomitant malignancies or previous malignancies with less than a 1-year disease-free interval at the time of signing consent.
  4. Pregnancy or lactation.
  5. Active uncontrolled systemic infection.
  6. 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.
  7. Known history of active tuberculosis.
  8. Current (non-infectious) pneumonitis, or a history of pneumonitis that required steroids.
  9. A live vaccine administered within 30 days of the first dose of study treatment.
  10. Receipt of any investigational product within 14 days or 5 half-lives prior to study treatment initiation, whichever is shortest.
  11. Prior intolerance to pembrolizumab or other anti-PD-1/PD-L1 agents.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04383938
Other Study ID Numbers  ICMJE A20-11195
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Aprea Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Aprea Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Joachim Gullbo, MD Theradex Oncology
PRS Account Aprea Therapeutics
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP