BGB-3245 for Solid Cancer

No longer recruiting at 13 trial locations

Overseen By MapKure

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MapKure, LLC

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: Severe disease, Cardiac disease, CNS metastases, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BGB-3245 (Brimarafenib) for individuals with advanced solid tumors that haven't responded to other treatments. The goal is to assess the safety and effectiveness of BGB-3245 in shrinking tumors. Participants should have a solid tumor with specific genetic changes, such as certain BRAF or NRAS mutations, and must have experienced cancer growth despite previous treatments. Those with measurable tumors who haven't had recent cancer treatments might be suitable for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking any systemic anticancer therapies, including chemotherapy, immunotherapy, and biologic therapy, before starting the study. Specifically, you must stop systemic chemotherapy 4-6 weeks before, and biologic therapy 5 times the half-life of the agent or ≤4 weeks before the first dose. Other medications are not specified, so consult with the trial team for more details.

Will I have to stop taking my current medications?

The trial requires that you stop taking any cancer therapy, including chemotherapy, immunotherapy, or other systemic anticancer treatments, before starting the study. You must not have received systemic chemotherapy within 4 to 6 weeks, or other treatments within a period of 5 times the half-life of the agent or 4 weeks, whichever is shorter, before the first dose.

Is there any evidence suggesting that BGB-3245 is likely to be safe for humans?

Research shows that BGB-3245 may help treat solid tumors with a specific mutation. In earlier studies, it showed promising results in fighting tumors. Importantly, BGB-3245 demonstrated a manageable safety profile, with most side effects being mild and treatable. Although detailed safety information is limited, its testing in early human trials ensures close monitoring of safety. Participants typically experience mild to moderate side effects, which are common in early trials. For safety concerns, consider discussing them with the trial coordinators or your doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about BGB-3245 because it targets cancers in a unique way. Unlike standard treatments for solid tumors, which often involve chemotherapy or radiation, BGB-3245 is a small molecule inhibitor that specifically targets the MAPK pathway—a key driver in many cancers. This targeted approach could mean fewer side effects and more effective treatment for patients whose cancers are driven by this pathway. Plus, it's administered orally, which is convenient compared to some treatments that require hospital visits for infusions.

What evidence suggests that BGB-3245 might be an effective treatment for solid cancer?

Research has shown that BGB-3245, the investigational treatment in this trial, may help shrink solid tumors with specific genetic changes in the MAPK pathway. In early human trials, 79% of patients experienced positive effects from this experimental treatment. It also maintains a manageable safety profile, crucial for those with advanced or difficult-to-treat cancers. Although these results are preliminary, they suggest that BGB-3245 could be effective for certain types of solid tumors. ^{2 5 6 7 8}

Who Is on the Research Team?

Brandon Beagle, MD

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have worsened after treatment or lack treatment options. They must have specific mutations in the BRAF, NRAS, or KRAS genes and can't be undergoing cancer therapy at the start. Those with certain medical conditions like HIV or active hepatitis, gastrointestinal issues affecting drug absorption, or symptomatic brain metastases are excluded.

Inclusion Criteria

My advanced cancer has worsened after treatment or I can't tolerate available treatments.

I have skin cancer with an NRAS mutation and agree to provide fresh tissue samples.

My skin cancer has an NRAS mutation.

Exclusion Criteria

I haven't had chemotherapy with nitrosourea or mitomycin C in the last 6 weeks.

I do not have any major health conditions that would make it unsafe for me to take the study drug.

I don't have symptoms from brain or spinal cancer spread, but if present, they're stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

BGB-3245 administered orally to determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 Dose (RP2D)

30 days

Dose Expansion

BGB-3245 administered orally to evaluate Objective Response Rate (ORR) in participants

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BGB-3245

Trial Overview The study tests BGB-3245's safety and effectiveness against advanced solid tumors with particular genetic mutations. It has two phases: Phase 1a includes various tumor types and mutations; Phase 1b focuses on four groups based on mutation type and cancer kind.

How Is the Trial Designed?

Group I: Phase 1b, Group 1: Dose Expansion Experimental Treatment 1 Intervention

BGB-3245 administered orally (PO)

Group II: Phase 1a: Dose Escalation Experimental Treatment 1 Intervention

BGB-3245 administered orally (PO)

Who Is Running the Clinical Trial?

MapKure, LLC

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

Brivanib, tested in a phase I study with 90 patients, showed a manageable toxicity profile at doses ranging from 180 to 800 mg, with the maximum tolerated dose identified as 800 mg per day.

The treatment demonstrated promising antiangiogenic and antitumor activity, with partial responses in some patients and significant decreases in tumor vascularity and permeability, supporting its potential for further investigation in phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors. Jonker, DJ., Rosen, LS., Sawyer, MB., et al.[2021]

In a pilot study involving 13 patients with advanced melanoma, breast cancer, and colon cancer, the drug PD-0325901 showed significant tolerability issues, particularly at doses of 15 mg twice daily or higher, leading to early termination of the study due to adverse effects like gait disturbance and memory impairment.

Despite the safety concerns, one patient achieved a complete response and five had stable disease, suggesting that PD-0325901 may have preliminary antitumor activity, warranting further investigation at lower doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer. Boasberg, PD., Redfern, CH., Daniels, GA., et al.[2021]

Methylene blue (MB), an FDA-approved drug, effectively inhibits PD-1 signaling, enhancing the activity of CD8+ cytotoxic T lymphocytes (CTL) against tumors.

In mouse models, MB not only boosts CTL function but also reduces the size of PD-L1 expressing tumors, suggesting it could be a promising new strategy for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blocking interaction between SHP2 and PD-1 denotes a novel opportunity for developing PD-1 inhibitors. Fan, Z., Tian, Y., Chen, Z., et al.[2022]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

In a study of 53 patients with advanced biliary cancers, the combination of erlotinib and bevacizumab demonstrated clinical activity, with 12% of patients achieving a partial response and 51% showing stable disease.

The treatment was generally well-tolerated, with the most common severe side effect being a rash, and median overall survival was 9.9 months, suggesting this combination could be a viable therapeutic option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study. Lubner, SJ., Mahoney, MR., Kolesar, JL., et al.[2022]

A review of seven targeted cancer therapies (sunitinib, pazopanib, bevacizumab, temsirolimus, axitinib, everolimus, and sorafenib) revealed that all these medications are associated with adverse events, highlighting the importance of monitoring patients closely.

Effective management strategies for these side effects can prevent them from becoming severe, which is crucial to maintaining the full efficacy of the treatments and avoiding unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. Alasker, A., Meskawi, M., Sun, M., et al.[2022]

Pemigatinib (compound 38) is a highly potent and selective inhibitor of FGFR1, FGFR2, and FGFR3, showing promise as a targeted cancer treatment due to its strong pharmacokinetic properties.

The U.S. FDA has granted accelerated approval for pemigatinib to treat adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma that has FGFR2 fusions or rearrangements, with ongoing trials to further assess its efficacy in patients with other FGFR alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. Wu, L., Zhang, C., He, C., et al.[2021]

In the phase I/II FIGHT-101 study involving 128 patients with advanced malignancies, pemigatinib demonstrated a manageable safety profile with no dose-limiting toxicities and a recommended phase II dose of 13.5 mg once daily.

The treatment showed preliminary efficacy, particularly in patients with FGFR fusions/rearrangements, achieving a 25% response rate, and prompting further studies in cholangiocarcinoma and other tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies. Subbiah, V., Iannotti, NO., Gutierrez, M., et al.[2022]

In a Phase 1 study involving patients with advanced solid tumors, OBI-3424 was administered at various doses, with the recommended Phase 2 dose (RP2D) established at 12 mg/m2 due to dose-limiting toxicities observed at higher doses.

The treatment was generally well tolerated, although 49% of patients experienced grade ≥3 adverse events, primarily anemia and thrombocytopenia, with one patient showing a partial response and 64% maintaining stable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, and clinical activity of OBI-3424 in patients with advanced or metastatic solid tumors. Tsimberidou, AM., Verschraegen, CF., Wesolowski, R., et al.[2023]

Brivanib alaninate is a first-in-class oral inhibitor that targets both FGF and VEGF receptors, showing promise in disrupting key pathways involved in cancer growth and angiogenesis.

Its dual action not only blocks VEGF receptors to prevent blood vessel formation but also targets FGF receptors, potentially overcoming resistance to VEGF therapies and inhibiting tumor growth, making it a strong candidate in late-phase clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brivanib: a review of development. Chou, T., Finn, RS.[2013]

In a phase 2 study involving 39 patients with refractory biliary tract cancer, regorafenib showed modest efficacy with a median overall survival of 5.4 months and a 6-month survival rate of 46.2%.

Despite its efficacy, regorafenib was associated with significant adverse events, as 71.8% of patients experienced grade 3/4 side effects, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-institutional phase 2 trial of regorafenib in refractory advanced biliary tract cancer. Kim, RD., Sanoff, HK., Poklepovic, AS., et al.[2021]

In a phase II trial involving 34 patients with advanced biliary tract cancers, the combination of regorafenib and avelumab showed antitumor activity, with a partial response in 13.8% of patients and stable disease in 37.9%.

The treatment was associated with manageable safety concerns, primarily hypertension and fatigue, and the presence of certain biomarkers like high levels of programmed cell death ligand 1 was linked to better outcomes, suggesting potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial. Cousin, S., Cantarel, C., Guegan, JP., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05580770

Mirdametinib + BGB-3245 in Advanced Solid Tumors A Phase 1/2a open-label, multicenter, dose escalation and expansion study of mirdametinib in combination with BGB-3245 in adult participants with ...

2. targetedonc.com targetedonc.com/view/bgb-3245-demonstrates-efficacy-in-solid-tumors-with-a-mutation-in-the-mapk-pathway

BGB-3245 Demonstrates Efficacy in Solid Tumors With a ... The investigational drug BGB-3245 showed encouraging anti-tumor activity with a manageable safety profile in a first-in-human phase 1a/1b trial.

3. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT031/725418/Abstract-CT031-A-first-in-human-phase-1a-1b-open

Abstract CT031: A first-in-human, phase 1a/1b, open-label ... Tmax was at ~2 h; BGB-3245 had a long terminal half-life and 7.4-fold average accumulation in exposure at steady-state. 79% of pts were efficacy ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04249843?tab=table

NCT04249843 | Study of Safety, Pharmacokinetics, and ... The study was terminated by the sponsor for reasons unrelated to safety. Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT04249843

Study of Safety, Pharmacokinetics, and Antitumor Activity ... "A Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors is ongoing; additional data from the dose expansion portion ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05580770

Mirdametinib + BGB-3245 in Advanced Solid Tumors A Phase 1/2a open-label, multicenter, dose escalation and expansion study of mirdametinib in combination with BGB-3245 in adult participants.

7. withpower.com withpower.com/trial/phase-1-neoplasms-1-2020-a81cd

BGB-3245 for Solid Cancer · Info for Participants The provided research does not contain specific safety data for BGB-3245 (Brimarafenib) in treating solid cancer. The studies mentioned focus on other drugs and ...

8. clinicaltrials.gov clinicaltrials.gov/ct2/show/record/NCT04249843

Study of Safety, Pharmacokinetics, and Antitumor Activity of ... The purpose of this study is to evaluate the safety, tolerability, and antitumor activity of BGB-3245 in participants with advanced or refractory solid tumors.