Breast CancerSmall Cell Lung CancerOvarian CancerGastric CancerHormone-receptor-positive Breast CancerHormone Receptor Positive HER-2 Negative Breast CancerAdvanced Solid TumorEndometrial CancerProstate CancerTNBC - Triple-Negative Breast CancerGastroEsophageal CancerBladder Cancer
Fulvestrant: Standard dose administered via intramuscular injection.
BGB-43395: Planned doses administered orally.
Study summary
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).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Part 1 (Dose Escalation) Inclusion Criteria:
* Monotherapy Cohorts: Participants with histologically or cytologically confirmed advanced or metastatic solid tumors potentially associated with CDK2 dependency including HR+/HER2- breast cancer, platinum refractory or resistant serous ovarian cancer (PROC), endometrial cancer, and others. Prior available standard-of-care systemic therapies for advanced or metastatic disease are required. The requirements for enrollment into a food effect evaluation cohort are the same as the monotherapy cohorts with the exception that participants with gastric cancer and gastroesophageal adenocarcinoma are excluded.
* Combination Cohorts (BG-68501 with fulvestrant with or without BGB-43395): Enrollment is restricted to only participants with HR+/HER2- BC. In regions where approved and available, participants must have received one or more lines of treatment for advanced/metastatic disease as well as prior endocrine therapy and a CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting. If applicable, the requirements for enrollment into a food effect evaluation cohort are the same as the combination cohorts.
Part 1 (Safety Expansion) and Part 2 (Dose Expansion) Inclusion Criteria:
* Participants with advanced, non-resectable, or metastatic HR+/HER2- BC or PROC, including fallopian tube or primary peritoneal cancer.
* PROC participants must have received:
* ≥ 1 line of platinum-containing chemotherapy for advanced disease.
* ≤ 4 prior therapeutic regimens in the advanced/metastatic setting.
* HR+/HER2- BC:
* Participants enrolled in regions where CDK4/6 inhibitors are approved and available must have received ≥ 1 line of therapy including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy or ADC treatments for advanced disease.
General Inclusion Criteria:
* Female participants with advanced or metastatic HR+/HER2- BC will be required to have ovarian function suppression using gonadotropin hormone-releasing hormone (GnRH) agonists (such as goserelin) or be postmenopausal.
* Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
* Adequate organ function.
* For dose escalation, participants with advanced solid tumors other than HR+/HER2- BC must have measurable disease per RECIST 1.1. Participants with HR+/HER2- BC with bone-only disease are eligible for dose escalation only. For safety expansion and dose expansion, all participants must have ≥1 measurable lesion per RECIST v 1.1.
General Exclusion Criteria:
* For all cohorts: Prior therapy selectively targeting CDK2 inhibition.
* For triple combination cohorts: Prior therapy targeting CDK2 or selectively targeting CDK4. Prior CDK4/6 inhibitor therapy is permitted and required in local regions where it is approved and available.
* Known leptomeningeal disease or uncontrolled, untreated brain metastasis. Participants with a history of treated central nervous system (CNS) metastases may be eligible if they meet additional criteria.
* Any malignancy ≤ 3 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, treated papillary thyroid carcinoma, or carcinoma in situ of the cervix or breast).
* Uncontrolled diabetes.
* Infection requiring systemic antibacterial, antifungal, or antiviral therapy antiviral therapy ≤ 28 days before the first dose of study drug(s), or symptomatic COVID-19 infection.
* Active hepatitis B infection or active hepatitis C infection.
* Any major surgical procedure ≤ 28 days before the first dose of study treatment(s).
* Prior allogeneic stem cell transplantation, or organ transplantation.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Primary outcome measure(s)
Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) — From the first dose of study drug(s) to 30 days after the last dose; approximately 6-12 months Number of participants with treatment-emergent AEs and SAEs.
Part 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-68501 — Up to approximately 24 months 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.
Part 1: Recommended dose(s) for Expansion (RDFE) of BG-68501 monotherapy in participants with solid tumors — Up to approximately 24 months RDFE of BG-68501 alone will be determined based upon the MTD or MAD.
Part 1: RDFE of BG-68501 in combination with fulvestrant and BGB-43395 in participants with HR+/HER2- BC — Up to approximately 24 months RDFE of BG-68501 in combination with fulvestrant and BGB-43395 will be determined based upon the MTD or MAD.
Part 2: Objective Response Rate (ORR) — Up to approximately 20 months 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.
Trial sites (24)
Facility
City
Region
Status
Hoag Memorial Presbyterian
Newport Beach
California
Florida Cancer Specialists and Research Institute
Lake Mary
Florida
Washington University School of Medicine
St Louis
Missouri
Titan Health Partners Llc Dba Astera Cancer Care
East Brunswick
New Jersey
Avera Cancer Institute
Sioux Falls
South Dakota
Mary Crowley Cancer Research
Dallas
Texas
Blacktown Cancer and Haematology Centre
Blacktown
New South Wales
Saint Vincents Hospital Sydney
Darlinghurst
New South Wales
Nepean Hospital
Kingswood
New South Wales
Genesiscare North Shore
St Leonards
New South Wales
Princess Alexandra Hospital
Woolloongabba
Queensland
Cancer Research South Australia
Adelaide
South Australia
Monash Health
Clayton
Victoria
Cancer Hospital Chinese Academy of Medical Sciences
Beijing
Beijing Municipality
Beijing Cancer Hospital
Beijing
Beijing Municipality
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
Guangzhou
Guangdong
Harbin Medical University Cancer Hospital
Harbin
Heilongjiang
Hunan Cancer Hospital
Changsha
Hunan
Shengjing Hospital of China Medical Universityhuaxiang Branch
Shenyang
Liaoning
The First Affiliated Hospital of Xian Jiaotong University
Xi'an
Shaanxi
Rambam Health Care Center
Haifa
Israel
Shaare Zedek Medical Center
Jerusalem
Israel
The Institute of Oncology, Arensia Exploratory Medicine
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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