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Bladder CancerPhase 1/2NCT04383938

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

A Phase 1/2 study testing APR-246 (eprenetapopt) + Pembrolizumab in people with Bladder Cancer and Gastric Cancer, run by Aprea Therapeutics at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APR-246 (eprenetapopt) + Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
8 sitesUnited States
Study dates
25 Jun 2020to 30 Apr 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Center

    Boston, Massachusetts, 02115

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Vanderbilt University

    Nashville, Tennessee, 37235

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55902

  • Washington University

    St Louis, Missouri, 63130

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
APR-246 (eprenetapopt) + Pembrolizumab
Keywords
Pembrolizumab, APR-246, Aprea, eprenetapopt
Medical subject headings
Urinary Bladder Neoplasms, Stomach Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APR-246 (eprenetapopt) + PembrolizumabDrug

    APR-246 D1-4 + Pembrolizumab D3

Study groups in NCT04383938
Study groupRoleWhat they receive
Safety Lead In-Phase 1 Dose Level 1ExperimentalAPR-246 4.5g/d with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced non-CNS primary tumors
Receives: Drug: APR-246 (eprenetapopt) + Pembrolizumab
Expansion 1- Gastric CancerExperimentalAPR-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
Receives: Drug: APR-246 (eprenetapopt) + Pembrolizumab
Expansion 2- Bladder CancerExperimentalAPR-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
Receives: Drug: APR-246 (eprenetapopt) + Pembrolizumab
Expansion 3 -NSCLCExperimentalAPR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced NSCLC.
Receives: Drug: APR-246 (eprenetapopt) + Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To Evaluate the Safety of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumors.

    To determine the Frequency of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) related to APR-246 in combination with pembrolizumab.

    Measured: Through study completion, approximately 1 year

  2. To Confirm the Recommended Phase 2 Dose (RP2D) for APR-246 in Combination With Pembrolizumab

    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

    Measured: Through safety lead in period, during cycle 1 (approximately 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2020
  2. Study start25 Jun 2020
  3. Primary completion30 Apr 2022
  4. Study completion30 Apr 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04383938
Sponsor's protocol ID
A20-11195
Status last verified
May 2025
First submitted
7 May 2020
Last updated
13 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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

    PubMed 36084396

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing APR-246 (eprenetapopt) + Pembrolizumab in people with Bladder Cancer and Gastric Cancer, run by Aprea Therapeutics at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To Evaluate the Safety of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumors. (time frame: Through study completion, approximately 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04383938, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2025; AzTrials last refreshed its copy on 6 Nov 2026.

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