This study is a first-in-human (FIH), Phase 1a/1b study of BG-68501, a cyclin-dependent kinase-2 inhibitor (CDK2i), to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-68501 in participants with advanced, nonresectable, or metastatic solid tumors as monotherapy and in combination with fulvestrant with or without BGB-43395, a selective CDK4 inhibitor, in adults with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC). The study will also identify a recommended dose for expansion (RDFE) for BG-68501 as monotherapy and in combination for subsequent disease directed studies. The study will be conducted in 2 parts: Part 1 (dose escalation and safety expansion, including evaluation of food effect) and Part 2 (dose expansion).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
258
Planned doses administered orally.
Standard dose administered via intramuscular injection.
Planned doses administered orally.
Hoag Memorial Presbyterian
Newport Beach, California, United States
RECRUITINGFlorida Cancer Specialists and Research Institute
Lake Mary, Florida, United States
RECRUITINGWashington University School of Medicine
St Louis, Missouri, United States
RECRUITINGTitan Health Partners Llc Dba Astera Cancer Care
East Brunswick, New Jersey, United States
Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with treatment-emergent AEs and SAEs.
Time frame: From the first dose of study drug(s) to 30 days after the last dose; approximately 6-12 months
Part 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-68501
MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached.
Time frame: Up to approximately 24 months
Part 1: Recommended dose(s) for Expansion (RDFE) of BG-68501 monotherapy in participants with solid tumors
RDFE of BG-68501 alone will be determined based upon the MTD or MAD.
Time frame: Up to approximately 24 months
Part 1: RDFE of BG-68501 in combination with fulvestrant and BGB-43395 in participants with HR+/HER2- BC
RDFE of BG-68501 in combination with fulvestrant and BGB-43395 will be determined based upon the MTD or MAD.
Time frame: Up to approximately 24 months
Part 2: Objective Response Rate (ORR)
ORR is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). CR and PR that is confirmed by repeat assessments, as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: Up to approximately 20 months
Part 1: ORR
ORR is defined as the percentage of participants with best overall response of CR or PR. CR and PR that is confirmed by repeat assessments, as assessed by the investigator using RECIST v1.1.
Time frame: Up to approximately 20 months
Part 2: Number of participants with AEs and SAEs
Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.
Time frame: From the first dose of study drug(s) to 30 days after the last dose; approximately 6-12 months
Parts 1 and 2: Duration of Response (DOR)
DOR is defined as the time from the first confirmed objective response by the investigator using RECIST v1.1 until the first documentation of disease progression after treatment initiation or death, whichever comes first.
Time frame: Up to approximately 20 months
Parts 1 and 2: Time to Response (TTR)
TTR is defined as the time from the treatment initiation to the first determination of overall response by the investigator using RECIST v1.1.
Time frame: Up to approximately 20 months
Parts 1 and 2: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with the best overall response, of a CR, PR, and stable disease assessed by the investigator using RECIST v1.1.
Time frame: Up to approximately 20 months
Parts 1 and 2: Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks assessed by the investigator using RECIST v1.1.
Time frame: Up to approximately 20 months
Part 1: Maximum observed plasma concentration (Cmax) for BG-68501 and BGB-43395
Time frame: 2 times in the first 2 months
Part 1: Observed plasma trough concentration (Ctrough) for BG-68501 and BGB-43395
Time frame: 5 times in the first 2 months
Part 1: Area under the concentration-time curve (AUC) for BG-68501 and BGB-43395
Time frame: 2 times in the first 2 months
Part 1: Half-life (t1/2) for BG-68501 and BGB-43395
Time frame: 2 times in the first 2 months
Part 2: Plasma concentrations for BG-68501 and BGB-43395
Time frame: 5 times in approximately 3 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Avera Cancer Institute
Sioux Falls, South Dakota, United States
RECRUITINGMary Crowley Cancer Research
Dallas, Texas, United States
RECRUITINGBlacktown Cancer and Haematology Centre
Blacktown, New South Wales, Australia
RECRUITINGSaint Vincents Hospital Sydney
Darlinghurst, New South Wales, Australia
RECRUITINGNepean Hospital
Kingswood, New South Wales, Australia
RECRUITINGGenesiscare North Shore
St Leonards, New South Wales, Australia
RECRUITING...and 14 more locations