Alrizomadlin (APG-115) in Subjects With BAP1 Cancer Syndrome and Early-Stage Mesothelioma

Summary

Background:

Mesothelioma is a rare cancer typically caused by exposure to asbestos and related fibers. Most people with mesothelioma survive less than 5 years after diagnosis. About 3000 people in the United States die from this disease each year. People with inherited mutations in the BAP1 gene \[called BAP1 Cancer Syndrome (BCS)\] are more likely to develop mesothelioma and other cancers such as melanomas and renal cell carcinomas without asbestos exposure. Almost all people with BCS develop multiple cancers, of which mesothelioma is the most commonly observed.

Objective:

To test a study drug (APG-115) in participants with BAP1 Cancer Syndrome (BCS) and early-stage mesothelioma.

Eligibility:

People aged 18 years and older with germline BAP1 mutations and early-stage mesothelioma that does not yet need standard treatment are eligible for protocol enrollment. Participants will be required to also enroll in NIH protocols 20-C-0106 and 06-C-0014 which allow for pre- and post-treatment biopsies and bloodwork to be obtained for additional research studies.

Design:

Participants will be screened. They will have a physical exam with blood tests. Their medical records will be reviewed. They will have imaging scans and tests of their heart and lung functions. A procedure using a flexible tube with a camera and light will be inserted into the participant s chest and abdomen through a small cut to look at the tumors and to collect a tissue sample (biopsy).

APG-115 capsules are taken by mouth. Participants will take the drug at home every other day for the first 13 days of the 21-day treatment cycles.

On the first day of each cycle, researchers will call or email participants to check on their health.

Participants will have blood tests 2 times a week during the first 2 cycles; after that, the blood tests will be weekly. These blood tests can be done at a local medical facility or at the NIH Clinical Center.

Participants may continue treatment for up to 16 cycles.

Imaging scans, biopsy, and other tests will be repeated after 8 and 16 cycles.

Conditions

• Mesothelioma
• Malignant Mesothelioma (MM)
• Early-stage Mesothelioma
• Subclinical Mesothelioma
• BRCA1-Associated Protein-1 (BAP1) Mutations
• Early-stage BAP1-associated Malignancies

Interventions

DRUG

alrizomadlin

Alrizomadlin (APG-115) oral tablets (150 mg) taken every other day on Days 1, 3, 5, 7, 9, 11, and 13 of every cycle (1 cycle=21 days) for 8 cycles (i.e., Course 1). Individuals with stable or responding disease may receive an additional 8 cycles (i.e., Course 2). Maximum (total) of 2 treatment courses.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• David S Schrump, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-03-16

Primary Completion

2026-03-16

Completion

2026-03-16

FDA Drug

Yes

Countries

• United States

Study Locations