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

June 1, 2022 updated by: Aprea Therapeutics

Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies

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.

Study Overview

Status

Completed

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

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • 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
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Center
    • Minnesota
      • 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
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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.
Drug: APR-246 (eprenetapopt) + Pembrolizumab
APR-246 D1-4 + Pembrolizumab D3
Experimental: Expansion 1
Patients with advanced gastric cancer.
Drug: APR-246 (eprenetapopt) + Pembrolizumab
APR-246 D1-4 + Pembrolizumab D3
Experimental: Expansion 2
Patients with advanced urothelial/bladder cancer.
Drug: APR-246 (eprenetapopt) + Pembrolizumab
APR-246 D1-4 + Pembrolizumab D3
Experimental: Expansion 3
Patients with advanced NSCLC.
Drug: APR-246 (eprenetapopt) + Pembrolizumab
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

This is where you will find people and organizations involved with this study.

Sponsor

Aprea Therapeutics

Investigators

  • Study Director: Joachim Gullbo, MD, Theradex Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 25, 2020

Primary Completion (Actual)

April 30, 2022

Study Completion (Actual)

April 30, 2022

Study Registration Dates

First Submitted

May 7, 2020

First Submitted That Met QC Criteria

May 11, 2020

First Posted (Actual)

May 12, 2020

Study Record Updates

Last Update Posted (Actual)

June 3, 2022

Last Update Submitted That Met QC Criteria

June 1, 2022

Last Verified

June 1, 2022

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

Yes

Studies a U.S. FDA-regulated device product

No

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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