BGB-3245 for Solid Cancer

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

110 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BGB-3245 to see if it can help patients with advanced or treatment-resistant cancers by stopping the cancer cells from growing.

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.

What data supports the idea that BGB-3245 for Solid Cancer is an effective drug?

The available research does not provide specific data on the effectiveness of BGB-3245 for Solid Cancer. Instead, it discusses other drugs like brivanib and pemigatinib, which are used for similar conditions. These drugs target specific pathways in cancer cells, showing promise in treating advanced solid tumors. However, without direct data on BGB-3245, we can't compare its effectiveness to these alternatives. ^{1 2 3 4 5}

What data supports the effectiveness of the drug BGB-3245 for solid cancer?

The research on similar drugs like pemigatinib, which targets FGFR (a protein involved in cell growth), shows promise in treating certain cancers by blocking these growth signals. This suggests that BGB-3245, which may have similar targets, could potentially be effective in treating solid cancers. ^{1 2 3 4 5}

What safety data is available for BGB-3245 (Brimarafenib) in treating solid cancer?

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 their safety profiles, such as brivanib, pemigatinib, and OBI-3424, but not BGB-3245. ^{1 2 4 6 7}

Is the drug BGB-3245 a promising treatment for solid cancer?

The information provided does not directly mention BGB-3245 or its effects on solid cancer. Therefore, based on the given data, we cannot determine if BGB-3245 is a promising treatment for solid cancer. ^{8 9 10 11 12}

Research Team

Brandon Beagle, MD

Principal Investigator

BeiGene

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. England 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. [2022]

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

Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. [2021]

4. England 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Brivanib: a review of development. [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. [2022]

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

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Blocking interaction between SHP2 and PD-1 denotes a novel opportunity for developing PD-1 inhibitors. [2022]

9. United States 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer. [2021]

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

A multi-institutional phase 2 trial of regorafenib in refractory advanced biliary tract cancer. [2021]