A Phase Ia/b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of PRMT5 Inhibitor BGB-58067 Alone and in Combination With Anticancer Agents in Patients With Advanced Solid Tumors
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Study Summary
To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency. To evaluate PRMT5 inhibitor in Patients with Non-small cell lung cancer and Solid Tumors
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 alone, in combination with BG-89894 (discontinued), in combination with standard of care therapy, and in combination with novel anticancer therapies in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.
The purpose of this study is to test how safe and helpful BGB-58067 is when given alone, in combination with standard of care therapy, and in combination with novel anticancer therapies in participants with advanced solid tumors and with MTAP deficiency. The main goals of this study are to ensure the treatments are safe by monitoring side effects and to understand how well patients respond to the treatment and whether their cancers shrink or disappear.
This study consists of dose escalation and dose expansion parts. During the dose escalation part, the study doctors will test different doses of the study drug(s) to find the recommended dose that people can take without having serious side effects. During the dose expansion part, the study doctors will test the study drug(s) in a larger number of people using the dose(s) identified from dose escalation.
- Participants must sign the Informed Consent Form and be capable of giving written informed consentEastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or Karnofsky Performance Scale (KPS) ≥ 70Life expectancy ≥ 3 monthsEvidence of homozygous loss of MTAP or lost MTAP expression in the tumor tissue; documented RAS mutation status or KRAS mutation is required for selected cohortsAble to provide tumor sample to meet the minimum tissue requirement for central MTAP deficiency testingParticipants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose diseases have progressed or recurred after receiving standard systemic therapy or radiotherapy, or for whom standard systemic therapy is not available or tolerated, or would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard treatment in the opinion of the investigator; participants with advanced, metastatic, or unresectable solid tumors who have not received prior systemic treatment or have received one cycle of standard-of-care therapies will be enrolled in selected cohortsAdequate organ function
- Prior treatment with any PRMT5 inhibitor or methionine adenosyltransferase 2a (MAT2A) inhibitorActive leptomeningeal disease or symptomatic spinal cord compressionUncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainageAny malignancy ≤ 2 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curativelySignificantly impaired pulmonary functionClinically significant infectionsSerologically active hepatitis B or C infectionKnown human immunodeficiency virus (HIV) infection. Participants with treated HIV infection may be included in Phase 1b if they meet certain criteriaHigh cardiovascular risk factorsQT interval corrected by Fridericia's method (QTcF) > 470 ms based on the screening triplicate 12-lead ECG records and/or a history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, or a family history of Long QT Syndrome)Toxicities (because of prior anticancer therapy) that have not recovered to baseline or stabilizedParticipants who are unable to swallow or with disease/procedure significantly affecting gastrointestinal functionFemale participants who are pregnant or are breastfeedingConcurrent participation in another therapeutic clinical study (participation in observational or noninterventional studies is allowed)
Clinical Study Information for Healthcare Providers
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