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Purpose

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).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1 Part A: Dose Escalation and Safety Expansion (BG-68501 Monotherapy) 		Sequential cohorts of increasing dose levels of BG-68501 will be evaluated as monotherapy.
  • Drug: BG-68501
    Planned doses administered orally.
Experimental
Part 1 Part B: Dose Escalation (BG-68501 + Fulvestrant) 		Sequential cohorts of increasing dose levels of BG-68501 will be evaluated in combination with fulvestrant.
  • Drug: BG-68501
    Planned doses administered orally.
  • Drug: Fulvestrant
    Standard dose administered via intramuscular injection.
Experimental
Part 1 Part C: Dose Escalation and Safety Expansion (BG-68501 + Fulvestrant + BGB-43395) 		Sequential cohorts of increasing dose levels of BG-68501 will be evaluated in combination with fulvestrant and BGB-43395.
  • Drug: BG-68501
    Planned doses administered orally.
  • Drug: Fulvestrant
    Standard dose administered via intramuscular injection.
  • Drug: BGB-43395
    Planned doses administered orally.
Experimental
Part 1: Food Effect Evaluation 		Participants will receive BG-68501 at a dose level that is determined safe and tolerable to evaluate food effect. Food effect may also be evaluated for BG-68501 in combination with fulvestrant.
  • Drug: BG-68501
    Planned doses administered orally.
  • Drug: Fulvestrant
    Standard dose administered via intramuscular injection.
Experimental
Part 2: Dose Expansion 		The RFDE for BG-68501 (as monotherapy and in combination with fulvestrant and BGB-43395) from Part 1 will be evaluated in selected tumor cohorts.
  • Drug: BG-68501
    Planned doses administered orally.
  • Drug: Fulvestrant
    Standard dose administered via intramuscular injection.
  • Drug: BGB-43395
    Planned doses administered orally.

Recruiting Locations

Hoag Memorial Presbyterian
Newport Beach, California 92663-4162

Washington University School of Medicine
St Louis, Missouri 63110-1010

Titan Health Partners Llc Dba Astera Cancer Care
East Brunswick, New Jersey 08816-4096

Avera Cancer Institute
Sioux Falls, South Dakota 57105-2108

Mary Crowley Cancer Research
Dallas, Texas 75230

More Details

Status
Recruiting
Sponsor
BeiGene

Study Contact

Study Director
1.877.828.5568
clinicaltrials@beigene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.