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

NCT ID: NCT04383938

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-25
• Study Completion Date: 2022-04-30

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Safety Lead In-Phase 1 Dose Level 1

APR-246 4.5g/d with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced non-CNS primary tumors

Group Type: EXPERIMENTAL

APR-246 (eprenetapopt) + Pembrolizumab

Intervention Type: DRUG

APR-246 D1-4 + Pembrolizumab D3

Expansion 1- Gastric Cancer

APR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced gastric or GEJ tumors

Group Type: EXPERIMENTAL

APR-246 (eprenetapopt) + Pembrolizumab

Intervention Type: DRUG

APR-246 D1-4 + Pembrolizumab D3

Expansion 2- Bladder Cancer

APR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced bladder or urothelial tumors

Group Type: EXPERIMENTAL

APR-246 (eprenetapopt) + Pembrolizumab

Intervention Type: DRUG

APR-246 D1-4 + Pembrolizumab D3

Expansion 3 -NSCLC

APR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced NSCLC.

Group Type: EXPERIMENTAL

APR-246 (eprenetapopt) + Pembrolizumab

Intervention Type: DRUG

APR-246 D1-4 + Pembrolizumab D3

Interventions

APR-246 (eprenetapopt) + Pembrolizumab

APR-246 D1-4 + Pembrolizumab D3

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aprea Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joachim Gullbo, MD

Role: STUDY_DIRECTOR

Theradex Oncology

Locations

Mayo Clinic

Phoenix, Arizona, United States

Mayo Clinic

Jacksonville, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Center

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Vanderbilt University

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

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 Oct;7(5):100573. doi: 10.1016/j.esmoop.2022.100573. Epub 2022 Sep 7.

Reference Type: DERIVED

PMID: 36084396 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

A20-11195

Identifier Type: -

Identifier Source: org_study_id