BGB-58067 for Solid Tumors

Recruiting at 55 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

237 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BGB-58067 (a PRMT5 inhibitor), to determine its safety and effectiveness in treating advanced solid tumors lacking the enzyme MTAP. The trial will evaluate the drug alone, with another experimental drug, BG-89894, and alongside standard cancer treatments. Individuals whose cancer has returned or worsened after standard treatments, or who cannot undergo standard treatments, might be suitable candidates, particularly if their tumors exhibit MTAP deficiency. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BGB-58067 is being tested for safety and effectiveness in treating advanced solid tumors. This trial marks its first use in humans, so information remains limited. In this early testing phase, safety is a primary focus. The treatment is typically administered in small doses to monitor reactions.

Researchers are studying the safety of BGB-58067, whether used alone, with BG-89894, or alongside standard care. The studies aim to assess how well patients tolerate the treatment. Although it is too early to determine its safety, the progression through trials suggests some confidence in its potential.

Participants in these studies will be closely monitored for side effects and will help establish the safest dose levels. This careful approach ensures that any risks are understood and managed as more information becomes available. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BGB-58067 because it offers a fresh approach to treating solid tumors. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, BGB-58067 is designed to target specific pathways involved in tumor growth, potentially leading to fewer side effects. Additionally, when combined with BG-89894 or standard therapy, it could enhance the overall effectiveness of treatment regimens. This precision in targeting makes BGB-58067 a promising candidate for improving outcomes in patients with solid tumors.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that BGB-58067 targets tumors with a specific deficiency by blocking a protein called PRMT5, which is linked to worse cancer outcomes. Early lab studies have shown promise, with BGB-58067 effectively stopping tumor growth. In this trial, participants may receive BGB-58067 as monotherapy or in combination with another drug, BG-89894. Initial tests suggest that the combination with BG-89894 may have even stronger anti-cancer effects, though more detailed results are still being gathered. Another arm of this trial will explore combining BGB-58067 with standard treatments, which might also improve effectiveness, but specific data remains limited. Overall, BGB-58067 has shown potential in lab settings, and researchers are eager to see its effects in people with advanced solid tumors. ^{2 4 5 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

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.

My doctor expects me to live for at least 3 more months.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Phase 1b: Dose Expansion and Optimization Experimental Treatment 3 Interventions

Recommended Dose(s) for Expansion (RDFE\[s\]) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy will be evaluated for selected indications and regimen(s) based on emerging data.

Group II: Phase 1a: BGB-58067 Monotherapy Dose Escalation and Safety Expansion Experimental Treatment 1 Intervention

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

Group III: Phase 1a: BGB-58067 + Standard of Care Combination Therapy Dose Escalation Experimental Treatment 2 Interventions

Sequential cohorts of increasing dose levels of BGB-58067 in combination with standard of care therapy will be evaluated.

Group IV: Phase 1a: BGB-58067 + BG-89894 Combination Therapy Dose Escalation Experimental Treatment 2 Interventions

Sequential cohorts of increasing dose levels of BGB-58067 in combination with BGB-89894 will be evaluated.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06589596

NCT06589596 | An Investigational Study of BGB-58067 As ... This new study will check how safe and helpful a potential anticancer drug called BGB-58067 is. This drug will be tested alone, in combination with BG-89894, ...

2. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT193/761416/Abstract-CT193-Trial-in-progress-A-first-in-human

A first-in-human phase 1a/b study of BGB-58067, an MTA ... Overexpression of PRMT5 is associated with poor clinical outcomes in a variety of cancers, including lung, colon, pancreas, and bladder cancer, ...

3. beonemedinfo.com beonemedinfo.com/CongressDocuments/VanTine_BGB-58067-101_AACR_Poster_2025.pdf

A first-in-human phase 1a/b study of BGB-58067, an MTA- ... PRMT5 inhibitor that selectively inhibits PRMT5 in tumors with MTAP deletion (Figure 1). – Preclinical evidence has shown the effectiveness of BGB‑58067 in ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2824%2903919-X/fulltext

First-in-human study of AMG 193, an MTA-cooperative ... Here, we report results of the completed monotherapy dose exploration evaluating AMG 193 in patients with MTAP-deleted solid tumors.

5. withpower.com withpower.com/trial/phase-1-neoplasms-9-2024-fa421

BGB-58067 for Solid Tumors This Phase 1 medical study run by BeiGene is evaluating whether BGB-58067 will have tolerable side effects & efficacy for patients with Solid Tumors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06589596

NCT06589596 | An Investigational Study of BGB-58067 As ... This new study will check how safe and helpful a potential anticancer drug called BGB-58067 is. This drug will be tested alone, in combination with BG-89894, ...

7. synapse.patsnap.com synapse.patsnap.com/drug/82d6fd190e4f46bdb93ae8fc9c456468

BGB-58067 - Drug Targets, Indications, Patents BeiGene is focused on growing its leadership in solid tumors with its PD-1 inhibitor TEVIMBRA ® (tislelizumab) and by advancing potential best-in-class ...