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Brief Title: 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

INTRODUCTION

  • Org Study ID: A20-11195
  • Secondary ID: N/A
  • NTC ID: NCT04383938
  • Sponsor: 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.

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.

  • Overall Status
    Recruiting
  • Start Date
    June 25, 2020
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: To evaluate the safety and tolerability of APR-246 in combination with pembrolizumab in subjects with solid tumors.

Primary Outcome 1 - Timeframe: Through study completion, approximately 1 year

Primary Outcome 2 - Measure: To confirm the maximum tolerated dose (MTD) for APR-246 in combination with pembrolizumab

Primary Outcome 2 - Timeframe: Through safety lead in period, approximately 6 months

CONDITION

  • Bladder Cancer
  • Gastric Cancer
  • Non Small Cell Lung Cancer
  • NSCLC
  • Urothelial Carcinoma
  • Advanced Solid Tumor

ELIGIBILITY

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Joachim Gullbo, MD

Role: Study Director

Affiliation: Theradex Oncology

Overall Contact

Name: Joachim Gullbo, MD

Phone: +1 617 804 6947

Email: info@aprea.com

LOCATION

Facility Status Contact
Facility: Mayo Clinic
Phoenix, Arizona 85054
United States
Status: Recruiting Contact: N/A
Facility: Mayo Clinic
Jacksonville, Florida 32224
United States
Status: Recruiting Contact: N/A
Facility: Massachusetts General Hospital
Boston, Massachusetts 02114
United States
Status: Recruiting Contact: N/A
Facility: Dana Farber Cancer Center
Boston, Massachusetts 02115
United States
Status: Recruiting Contact: N/A
Facility: Mayo Clinic
Rochester, Minnesota 55902
United States
Status: Recruiting Contact: N/A
Facility: Washington University
Saint Louis, Missouri 63130
United States
Status: Recruiting Contact: N/A
Facility: Vanderbilt University
Nashville, Tennessee 37235
United States
Status: Recruiting Contact: N/A
Facility: MD Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A