Clinical trial NCT06257264: A Study to Examine the Safety of Different Doses of BG-68501 Given to Participants With Advanced-Stage Tumors
Official title: A Phase 1a/1b Study of BG-68501, a Selective CDK2 Inhibitor, in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Small Cell Lung Cancer
Ovarian Cancer
Gastric Cancer
Hormone-receptor-positive Breast Cancer
Hormone Receptor Positive HER-2 Negative Breast Cancer
Advanced Solid Tumor
Endometrial Cancer
Prostate Cancer
TNBC - Triple-Negative Breast Cancer
GastroEsophageal Cancer
Bladder Cancer
Keywords: breast cancer
small cell lung cancer
ovarian cancer
gastric cancer
cdk2 inhibitor
BG-68501
HR+ HER2- breast cancer
endometrial cancer
prostate cancer
BGB-43395
bladder cancer
urothelial cancer
gastroesophageal cancer
cdk4 inhibitor
fulvestrant
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-02-13
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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 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. 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 outcomes:
measure: Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; approximately 6-12 months
measure: Part 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-68501
timeFrame: Up to approximately 24 months
measure: Part 1: Recommended dose(s) for Expansion (RDFE) of BG-68501 monotherapy in participants with solid tumors
timeFrame: Up to approximately 24 months
measure: Part 1: RDFE of BG-68501 in combination with fulvestrant and BGB-43395 in participants with HR+/HER2- BC
timeFrame: Up to approximately 24 months
measure: Part 2: Objective Response Rate (ORR)
timeFrame: Up to approximately 20 months
Secondary outcomes:
measure: Part 1: ORR
timeFrame: Up to approximately 20 months
measure: Part 2: Number of participants with AEs and SAEs
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; approximately 6-12 months
measure: Parts 1 and 2: Duration of Response (DOR)
timeFrame: Up to approximately 20 months
measure: Parts 1 and 2: Time to Response (TTR)
timeFrame: Up to approximately 20 months
measure: Parts 1 and 2: Disease Control Rate (DCR)
timeFrame: Up to approximately 20 months
measure: Parts 1 and 2: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 20 months
measure: Part 1: Maximum observed plasma concentration (Cmax) for BG-68501 and BGB-43395
timeFrame: 2 times in the first 2 months
measure: Part 1: Observed plasma trough concentration (Ctrough) for BG-68501 and BGB-43395
timeFrame: 5 times in the first 2 months
measure: Part 1: Area under the concentration-time curve (AUC) for BG-68501 and BGB-43395
timeFrame: 2 times in the first 2 months
measure: Part 1: Half-life (t1/2) for BG-68501 and BGB-43395
timeFrame: 2 times in the first 2 months
measure: Part 2: Plasma concentrations for BG-68501 and BGB-43395
timeFrame: 5 times in approximately 3 months
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Hoag Memorial Presbyterian
state: California
city: Lake Mary
country: United States
facility: Florida Cancer Specialists and Research Institute
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: East Brunswick
country: United States
facility: Titan Health Partners Llc Dba Astera Cancer Care
state: New Jersey
city: Sioux Falls
country: United States
facility: Avera Cancer Institue
state: South Dakota
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Darlinghurst
country: Australia
facility: Saint Vincents Hospital Sydney
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Genesiscare North Shore
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Cancer Research South Australia
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Shenyang
country: China
facility: Shengjing Hospital Affiliated of China Medical University
state: Liaoning
city: Xian
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
state: Shaanxi
city: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
state: Sichuan
city: Haifa
country: Israel
facility: Rambam Health Care Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: BundangGu SeongnamSi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: IlsandongGu GoyangSi
country: Korea, Republic of
facility: National Cancer Center (Korea)
state: Gyeonggi-do
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Chisinau
country: Moldova, Republic of
facility: The Institute of Oncology, Arensia Exploratory Medicine
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: