BGB-58067 for Solid Tumors

Recruiting at 48 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must not be taking: PRMT5 inhibitors, MAT2A inhibitors

Disqualifiers: HIV, Hepatitis B/C, High cardiovascular risk, others

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

Compensation: Varies

Number of Visits: Unknown

92 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multicenter, first-in-human dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-58067 as monotherapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug BGB-58067 for solid tumors?

Research on PRMT5 inhibitors, similar to BGB-58067, shows promising results in treating various cancers. For example, PRMT5 inhibitors have shown tumor-suppressive effects in pancreatic, colorectal, and triple-negative breast cancers, and have led to partial responses in adenoid cystic carcinoma and a complete response in a specific type of brain cancer. ^{1 2 3 4 5}

How is the drug BGB-58067 different from other treatments for solid tumors?

BGB-58067 is a PRMT5 inhibitor, which is a new type of cancer treatment that targets an enzyme involved in cancer cell growth and survival. This drug is unique because it can potentially work alone or in combination with other therapies, especially in cancers with specific genetic mutations or deficiencies in DNA repair. ^{1 2 5 6 7}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for adults with advanced solid tumors that have lost MTAP expression, who've tried standard treatments without success or can't tolerate them. They must be able to consent, have a life expectancy of at least 3 months, and provide a tumor sample for testing.

Inclusion Criteria

I can provide a sample of my tumor for testing.

I can sign the consent form and understand what it means.

I am mostly active and can care for myself.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a: Dose Escalation and Safety Expansion

Sequential cohorts of increasing dose levels of BGB-58067 as monotherapy will be evaluated

Approximately 1.5 years

Phase 1b: Dose Expansion and Optimization

Recommended Dose(s) for Expansion (RDFE[s]) of BGB-58067 as monotherapy will be evaluated for selected indications based on emerging data

Approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BGB-58067

Trial Overview The study tests BGB-58067 as a solo treatment in people with specific advanced solid tumors lacking MTAP. It's an early-stage trial to check the drug's safety, how it affects the body, and its initial effectiveness against cancer.

Participant Groups

Group I: Phase 1b: Dose Expansion and Optimization Experimental Treatment 1 Intervention

Recommended Dose(s) for Expansion (RDFE\[s\]) of BGB-58067 as monotherapy will be evaluated for selected indications based on emerging data.

Group II: Phase 1a: Dose Escalation and Safety Expansion Experimental Treatment 1 Intervention

Sequential cohorts of increasing dose levels of BGB-58067 as monotherapy will be evaluated.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

In a Phase 1 study involving 90 patients with advanced solid tumors or non-Hodgkin lymphomas, JNJ-64619178, a PRMT5 inhibitor, showed manageable dose-dependent toxicity, with thrombocytopenia being the only dose-limiting side effect.

The drug demonstrated preliminary antitumor activity, particularly in patients with adenoid cystic carcinoma, achieving an objective response rate of 11.5% and a median progression-free survival of 19.1 months, suggesting potential for further development in this specific cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors. Vieito, M., Moreno, V., Spreafico, A., et al.[2023]

PRMT5 inhibitors, a new class of cancer treatments, have shown promising preliminary efficacy, including partial responses in adenoid cystic carcinoma and a durable complete response in glioblastoma multiforme with specific mutations.

These inhibitors demonstrate potential benefits both alone and in combination with other therapies, particularly for cancers with splicing mutations and DNA damage repair deficiencies, indicating a multifaceted approach to tumor suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors in Oncology Clinical Trials: A review. Feustel, K., Falchook, GS.[2022]

A novel PRMT5 inhibitor, compound 43g, demonstrated significant antitumor activity across various cancer cell lines and effectively reduced symmetric arginine dimethylation levels, which is linked to cancer progression.

Compound 43g selectively inhibited PRMT5 without affecting other protein arginine methyltransferase isoforms, suggesting a targeted approach that could minimize side effects in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of novel PRMT5 inhibitors bearing a methylpiperazinyl moiety. Bai, X., Zhai, Z., Zhao, X., et al.[2022]

PRMT5 is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), and its overexpression promotes cancer progression, making it a potential therapeutic target.

The newly discovered compound PR5-LL-CM01 effectively inhibits PRMT5 and shows greater anti-tumor efficacy than the existing PRMT5 inhibitor EPZ015666, suggesting it could be a promising candidate for future drug development against these challenging cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adapting AlphaLISA high throughput screen to discover a novel small-molecule inhibitor targeting protein arginine methyltransferase 5 in pancreatic and colorectal cancers. Prabhu, L., Wei, H., Chen, L., et al.[2022]

PRMT5 is differentially expressed and localized in triple-negative breast cancer (TNBC), with high levels correlating to poorer patient prognosis, indicating its potential as a therapeutic target.

Inhibition of PRMT5 using the small-molecule inhibitor EPZ015666 effectively reduces cell proliferation and tumor progression in TNBC models, suggesting that targeting PRMT5 could be a promising treatment strategy, especially in combination with EGFR inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein arginine methyltransferase 5: A novel therapeutic target for triple-negative breast cancers. Vinet, M., Suresh, S., Maire, V., et al.[2021]

A genome-wide CRISPR/Cas9 screen identified TP53 as a key sensitizer and MSI2 as a driver of resistance to the PRMT5 inhibitor GSK-591, suggesting that mutations in TP53 can predict resistance to this treatment.

Combining PRMT5 inhibition with either MSI2 or BCL-2 inhibition shows promise in reducing cell growth and promoting apoptosis in lymphoma, indicating a potential new therapeutic strategy for this cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma. Erazo, T., Evans, CM., Zakheim, D., et al.[2023]

PRMT5 is highly expressed in colorectal cancer (CRC) cells and tissues, and its down-regulation significantly suppresses CRC cell proliferation and progression through the cell cycle.

The mechanism by which PRMT5 promotes CRC growth and epithelial-mesenchymal transition (EMT) involves the activation of the EGFR/Akt/GSK3β signaling pathway, suggesting that targeting PRMT5 could be a promising therapeutic strategy for CRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRMT5 regulates colorectal cancer cell growth and EMT via EGFR/Akt/GSK3β signaling cascades. Yan, Y., Zhao, P., Wang, Z., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors in Oncology Clinical Trials: A review. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Discovery of novel PRMT5 inhibitors bearing a methylpiperazinyl moiety. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Adapting AlphaLISA high throughput screen to discover a novel small-molecule inhibitor targeting protein arginine methyltransferase 5 in pancreatic and colorectal cancers. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Protein arginine methyltransferase 5: A novel therapeutic target for triple-negative breast cancers. [2021]

6. England pubmed.ncbi.nlm.nih.gov

TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

PRMT5 regulates colorectal cancer cell growth and EMT via EGFR/Akt/GSK3β signaling cascades. [2021]