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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04383938
Recruitment Status : Recruiting
First Posted : May 12, 2020
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Aprea Therapeutics

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.

Condition or disease Intervention/treatment Phase
Bladder Cancer Gastric Cancer Non Small Cell Lung Cancer NSCLC Urothelial Carcinoma Advanced Solid Tumor Drug: APR-246 (eprenetapopt) + Pembrolizumab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies
Actual Study Start Date : June 25, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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.

  2. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04383938


Contacts
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Contact: Eyal Attar, MD +1 617 804 6947 info@aprea.com

Locations
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United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63130
Sponsors and Collaborators
Aprea Therapeutics
Investigators
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Study Director: Joachim Gullbo, MD Theradex Oncology
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Responsible Party: Aprea Therapeutics
ClinicalTrials.gov Identifier: NCT04383938    
Other Study ID Numbers: A20-11195
First Posted: May 12, 2020    Key Record Dates
Last Update Posted: July 1, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aprea Therapeutics:
Pembrolizumab
APR-246
Aprea
eprenetapopt
Additional relevant MeSH terms:
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Carcinoma, Transitional Cell
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents