Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: MapKure, LLC
No Placebo Group
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.
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.
12345What 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.
12467Eligibility 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.
+4 more
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.
+4 more
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Phase 1b, Group 1: Dose ExpansionExperimental Treatment1 Intervention
BGB-3245 administered orally (PO)
Group II: Phase 1a: Dose EscalationExperimental Treatment1 Intervention
BGB-3245 administered orally (PO)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MD AndersonHouston, TX
Cedars Sinai Medical CenterBeverly Hills, CA
Memorial Sloan Kettering Cancer CenterNew York, NY
Massachusetts General HospitalBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
MapKure, LLCLead Sponsor
References
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]This study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of brivanib in patients with advanced/metastatic solid tumors.
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]The phase I/II FIGHT-101 study (NCT02393248) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of pemigatinib, a potent and selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor, as monotherapy or in combination therapy, for refractory advanced malignancies, with and without fibroblast growth factor (FGF) and receptor (FGFR) gene alterations.
Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. [2021]Aberrant activation of FGFR has been linked to the pathogenesis of many tumor types. Selective inhibition of FGFR has emerged as a promising approach for cancer treatment. Herein, we describe the discovery of compound 38 (INCB054828, pemigatinib), a highly potent and selective inhibitor of FGFR1, FGFR2, and FGFR3 with excellent physiochemical properties and pharmacokinetic profiles. Pemigatinib has received accelerated approval from the U.S. Food and Drug Administration for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement. Additional clinical trials are ongoing to evaluate pemigatinib in patients with FGFR alterations.
Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, and clinical activity of OBI-3424 in patients with advanced or metastatic solid tumors. [2023]Report of a Phase 1 dose-escalation study of OBI-3424 monotherapy in patients with advanced solid tumors (NCT03592264).
Brivanib: a review of development. [2013]The development of new agents in oncology has focused on disrupting key pathways in oncogenesis. Both malignant angiogenesis and peptide growth factor signaling have been studied extensively and have been validated for cancer treatment. While antibody-directed therapeutics offer increased specificity, small-molecule tyrosine kinase inhibitors often have the ability to hit multiple targets. Brivanib alaninate (BMS582664) is an oral, potent selective inhibitor of both the FGF and VEGF family of receptors. It is a first-in-class FGF/VEGF inhibitor now in late-phase clinical trials. Besides its antiangiogenic activity from blocking VEGF receptor 1-3, its ability to disrupt FGF receptors 1-3 has been suggested to add additional antiangiogenic activity, overcome resistance from VEGF blockade, and block FGF-dependent tumor proliferation. In this review, we will discuss the preclinical science driving brivanib's development and the clinical data generated to date.
A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. [2022]To provide an updated review of adverse events associated with sunitinib, pazopanib, bevacizumab, temsirolimus, axitinib, everolimus and sorafenib and their management.
Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]There have been unique adverse events reported with targeted blockade of programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA4), including immune mediated toxicities. Recently, there have been reports of hepatitis B reactivation (HBVr) occurring with PD-1/PD-L1 inhibitors, which may result in treatment delays, interruptions, or discontinuation. This retrospective literature review and analysis of the Food and Drug Administration's (FDA) Adverse Events Reporting System (FAERS) queried reported cases of "Hepatitis B reactivation" reported with the PD-1/PD-L1 inhibitors "Pembrolizumab," "Atezolizumab," "Nivolumab," "Durvalumab," "Avelumab," and "Ipilimumab" from initial FDA approval to June 30, 2020. Disproportionality signal analysis was determined by calculating a reporting odds ratio (ROR) and 95% confidence intervals (CI). The ROR was considered significant when the lower and upper limits of the 95% CI were >1 and confirmed by the Fisher exact test (P
Blocking interaction between SHP2 and PD-1 denotes a novel opportunity for developing PD-1 inhibitors. [2022]Small molecular PD-1 inhibitors are lacking in current immuno-oncology clinic. PD-1/PD-L1 antibody inhibitors currently approved for clinical usage block interaction between PD-L1 and PD-1 to enhance cytotoxicity of CD8+ cytotoxic T lymphocyte (CTL). Whether other steps along the PD-1 signaling pathway can be targeted remains to be determined. Here, we report that methylene blue (MB), an FDA-approved chemical for treating methemoglobinemia, potently inhibits PD-1 signaling. MB enhances the cytotoxicity, activation, cell proliferation, and cytokine-secreting activity of CTL inhibited by PD-1. Mechanistically, MB blocks interaction between Y248-phosphorylated immunoreceptor tyrosine-based switch motif (ITSM) of human PD-1 and SHP2. MB enables activated CTL to shrink PD-L1 expressing tumor allografts and autochthonous lung cancers in a transgenic mouse model. MB also effectively counteracts the PD-1 signaling on human T cells isolated from peripheral blood of healthy donors. Thus, we identify an FDA-approved chemical capable of potently inhibiting the function of PD-1. Equally important, our work sheds light on a novel strategy to develop inhibitors targeting PD-1 signaling axis.
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]Biliary cancers overexpress epidermal growth factor receptor (EGFR), and angiogenesis has been correlated with poor outcome. Erlotinib, an EGFR tyrosine kinase inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor have each been shown to have activity in biliary cancer. The primary objective of this study was to evaluate the response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included overall survival (OS), time to progression (TTP), VEGF levels, and molecular studies of EGFR and k-ras.
Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial. [2022]Regorafenib has shown substantial clinical activity in patients with advanced biliary tract cancers (BTCs). Preclinical data suggested that this drug modulates antitumour immunity and is synergistic with immune checkpoint inhibition.
Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer. [2021]To assess further the tolerability and preliminary antitumor activity of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer.
A multi-institutional phase 2 trial of regorafenib in refractory advanced biliary tract cancer. [2021]Regorafenib is an oral multikinase inhibitor targeting angiogenesis, oncogenesis, and cancer proliferation/metastasis. This study evaluated the efficacy of regorafenib in refractory biliary tract cancer (BTC) in a multi-institutional phase 2 study.