A Study to Examine the Safety of Different Doses of BG-68501 Given to Participants With Advanced-Stage Tumors

BeiGene

Status and phase: Enrolling; Phase 1

Conditions: Breast Cancer; TNBC - Triple-Negative Breast Cancer; Small Cell Lung Cancer; Hormone-receptor-positive Breast Cancer; Advanced Solid Tumor; Ovarian Cancer; Endometrial Cancer; Bladder Cancer; Gastric Cancer; Hormone Receptor Positive HER-2 Negative Breast Cancer; GastroEsophageal Cancer; Prostate Cancer

Treatments: Drug: BGB-43395; Drug: BG-68501; Drug: Fulvestrant

Study type: Interventional

Funder types: Industry

Identifiers

NCT06257264

CTR20243059 (Registry Identifier)

BG-68501-101

2024-517324-19-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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) and Part 2 (dose expansion).

Enrollment: 138 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.
• 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.

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.
• History of hepatitis B 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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138 participants in 4 patient groups

Part 1 Part A: Dose Escalation and Safety Expansion (BG-68501 Monotherapy)

Experimental group

Description:

Sequential cohorts of increasing dose levels of BG-68501 will be evaluated as monotherapy.

Treatment:

Drug: BG-68501

Part 1 Part B: Dose Escalation (BG-68501 + Fulvestrant)

Experimental group

Description:

Sequential cohorts of increasing dose levels of BG-68501 will be evaluated in combination with fulvestrant.

Treatment:

Drug: Fulvestrant

Drug: BG-68501

Part 1 Part C: Dose Escalation and Safety Expansion (BG-68501 + Fulvestrant + BGB-43395)

Experimental group

Description:

Sequential cohorts of increasing dose levels of BG-68501 will be evaluated in combination with fulvestrant and BGB-43395.

Treatment:

Drug: Fulvestrant

Drug: BG-68501

Drug: BGB-43395

Part 2: Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: Fulvestrant

Drug: BG-68501

Drug: BGB-43395