Alrizomadlin for Mesothelioma

Overseen By Deneise C Francis, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticoagulants, CYP3A4/3A5 inhibitors

Disqualifiers: Cardiovascular disease, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new drug, Alrizomadlin (also known as APG-115), for individuals with early-stage mesothelioma linked to a specific genetic condition called BAP1 Cancer Syndrome. Mesothelioma is a rare cancer often caused by asbestos exposure, but those with BAP1 mutations can develop it without such exposure. The trial seeks participants with BAP1 mutations and early-stage mesothelioma that does not yet require standard treatments like surgery or chemotherapy. Eligible participants can help researchers understand how the drug affects the cancer. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking certain medications like CYP3A4/3A5 inhibitors or inducers, P-glycoprotein inhibitors, or therapeutic anticoagulants within two weeks before starting the trial.

Is there any evidence suggesting that Alrizomadlin (APG-115) is likely to be safe for humans?

Research has shown that Alrizomadlin (APG-115) has been generally safe in earlier studies. In one study, 27 patients took a 150 mg dose, and nearly half experienced serious side effects. These side effects were severe but linked to the treatment. Importantly, earlier research also found that Alrizomadlin was usually well-tolerated and might help treat certain types of tumors.

This trial is in the middle phase, indicating some evidence of the drug's safety, but more research is needed for confirmation. This stage often examines how well people tolerate the treatment and what side effects might occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for mesothelioma?

Alrizomadlin is unique because it targets a specific protein called MDM2, which plays a role in the growth of mesothelioma tumors. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, Alrizomadlin aims to restore the function of a tumor-suppressor protein called p53 by inhibiting MDM2. Researchers are excited about this treatment because it offers a more targeted approach, potentially leading to fewer side effects and improved outcomes for patients with mesothelioma.

What evidence suggests that Alrizomadlin might be an effective treatment for mesothelioma?

Research has shown that Alrizomadlin, also known as APG-115, may help treat certain cancers. In earlier studies, it was effective against tumors with specific genetic features, such as MDM2 amplification and TP53 wild-type status. For patients with adenoid cystic carcinoma (ACC), Alrizomadlin stopped disease progression in some cases. Although researchers are still learning about its effects on mesothelioma, these early results suggest it might also work for similar conditions. This trial will evaluate Alrizomadlin's potential to manage early-stage mesothelioma in people with BAP1 Cancer Syndrome. ^{1 2 3 4 5}

Who Is on the Research Team?

David S Schrump, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage mesothelioma, a type of cancer that affects the lining of the lungs, and who have BAP1 Cancer Syndrome. Participants should carry specific genetic changes known as BAP1 mutations.

Inclusion Criteria

Nursing participants must discontinue nursing during the study

Willingness to co-enroll on other specified studies for data collection

Agreement to use effective contraception

Exclusion Criteria

QTcF interval > 470 ms

Positive Hepatitis A, B, or C serological test

Seropositive for human immunodeficiency virus (HIV) infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive APG-115 orally every other day for the first 13 days of a 21-day cycle, up to 16 cycles

48 weeks

Blood tests 2 times a week during the first 2 cycles, then weekly

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) for safety assessment

Extension

Participants with stable disease or disease regression may continue treatment for an additional 8 cycles

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alrizomadlin (APG-115)

Trial Overview The study is testing alrizomadlin (APG-115) to see if it can stabilize or improve mesothelioma in patients with BAP1 Cancer Syndrome. It's a phase II trial, which means they're looking at how well the drug works and checking its safety.

How Is the Trial Designed?

Group I: 1/ Arm 1 Experimental Treatment 1 Intervention

APG-115

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The MESOMARK assay for measuring soluble mesothelin-related peptides (SMRP) is a reliable and robust tool, showing high precision and stability, making it suitable for clinical use in detecting malignant pleural mesothelioma (MPM).

In a study of 500 cancer patients, including 88 with MPM, the assay revealed significantly elevated SMRP levels in MPM patients (7.5 nmol/L) compared to healthy individuals (1.5 nmol/L), indicating its potential as a biomarker for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MESOMARK: a potential test for malignant pleural mesothelioma. Beyer, HL., Geschwindt, RD., Glover, CL., et al.[2022]

A screening of 1170 FDA-approved drugs identified cephalomannine, ouabain, thonzonium bromide, and emetine as highly effective against malignant pleural mesothelioma (MPM) cell lines, showing significant cytotoxicity and inhibition of cell proliferation.

These drugs, except for alexidine, demonstrated the ability to activate caspases and inhibit clonogenic ability across multiple MPM cell lines, suggesting they could be promising candidates for repurposing in MPM treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Drug Screening Revealed Novel Potential Agents against Malignant Pleural Mesothelioma. Dell'Anno, I., Melani, A., Martin, SA., et al.[2023]

Malignant mesothelioma is a challenging cancer primarily caused by environmental factors like asbestos, and most patients are not suitable for surgery or radiation, leaving cytotoxic agents as the main treatment option.

Recent trials have shown that pemetrexed, when combined with cisplatin, can achieve a response rate of 14.1% and a 1-year survival rate of 47.8%, indicating potential efficacy in treating this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging insights into the biology and therapy of malignant mesothelioma. Vogelzang, NJ.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06654050

Study Details | NCT06654050 | Alrizomadlin (APG-115) in ... To determine stabilization or disease improvement rates in participants with early-stage mesotheliomas arising in the context of BAP1 Cancer Syndrome (BCS) ...

2. withpower.com withpower.com/trial/phase-2-early-stage-bap1-associated-malignancies-9-2024-57f42

Alrizomadlin for Mesothelioma · Info for Participants This trial is for individuals with early-stage mesothelioma, a type of cancer that affects the lining of the lungs, and who have BAP1 Cancer Syndrome.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06654050?utm_source=trialradar

Alrizomadlin (APG-115) in Subjects With BAP1 Cancer ... Background: Mesothelioma is a rare cancer typically caused by exposure to asbestos and related fibers. Most people with mesothelioma survive less than 5 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11452328/

A first-in-human phase I study of a novel MDM2/p53 ... Alrizomadlin demonstrated a promising antitumor effect in MDM2-amplified and TP53 wild-type tumors. •. Durable tumor remission and altered ...

5. synapse.patsnap.com synapse.patsnap.com/drug/300b4908d88a496abcea294fcf93dd5c

Alrizomadlin - Drug Targets, Indications, Patents In the monotherapy arm, 17 patients were efficacy-evaluable. The ORR was 16.7%, and the DCR was 100% in 12 patients with ACC. The DCR was 80% in 5 patients with ...