This is a dose escalation and dose expansion study to compare how well BGB-43395, a selective cyclin-dependent kinase 4 (CDK4) inhibitor, works as monotherapy or in combination with fulvestrant, letrozole, or elacestrant in participants with hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) breast cancer (BC) and other advanced solid tumors. The main purpose of this study is to explore the recommended dosing for BGB-43395.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Phase 1a (Dose Escalation): Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors associated with dependency on CDK4, including HR+ breast cancer, ovarian cancer, endometrial cancer, non-small cell lung cancer, and others. For combination with elacestrant, participants must have received at least 1 prior line of treatment for advanced/metastatic disease including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting.
Phase 1a Safety Expansion: For combination with fulvestrant in regions where approved and available, participants with HR+ breast cancer must have received at least 1 prior line of treatment including endocrine therapy and a CDK4/6 inhibitor. For combination with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease.
Phase 1b: Participants with HR+/HER2- breast cancer.
Phase 1b: For combination with fulvestrant, participants with HR+/HER2- breast cancer enrolled in regions where CDK4/6 inhibitors are approved and available must have received 1-2 lines of therapy for advanced/metastatic disease including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy for advanced disease. Prior cytotoxic treatment is prohibited. For combination cohorts with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease.
Disqualifiers
Known leptomeningeal disease or uncontrolled, untreated brain metastases.
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, or carcinoma in situ of the cervix or breast).
Uncontrolled diabetes.
Infection requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 28 days before the first dose of study drug(s), or symptomatic COVID-19 infection.
Trial design
Design model
Sequential
Treatments tested in this trial
BGB-43395
Drug
Planned doses administered orally.
Fulvestrant
Drug
Standard dose administered via intramuscular injection.
Letrozole
Drug
Standard dose administered orally as a tablet.
Elacestrant
Drug
Standard dose administered orally as a tablet.
Anti-Diarrheal Agent
Drug
Administered orally as a tablet.
Treatment groups
399 Participants
are divided into 5 treatment groups
Group A: Dose EscalationExperimental treatment 4 interventions
Group B: Safety ExpansionExperimental treatment 3 interventions
Group C: Dose Expansion Cohort 1Experimental treatment 2 interventions
Group D: Dose Expansion Cohort 2Experimental treatment 2 interventions
Group E: Dose Expansion Cohort 3Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.
Time frame
Up to approximately 60 months
2
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395
MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate of 28%. MAD is defined as the highest dose administered if MTD is not reached.
Time frame
Up to approximately 60 months
3
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395
RDFE of BGB-43395 alone or in combination with fulvestrant, letrozole, or elacestrant will be determined based upon the MTD or MAD.
Time frame
Up to approximately 60 months
4
Phase 1b: Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have confirmed complete response (CR) or partial response (PR) assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame
Up to approximately 60 months
Secondary outcomes
1
Phase 1a: ORR
ORR is defined as the percentage of participants who have confirmed CR or PR assessed by the investigator using RECIST v1.1.
Time frame
Up to approximately 60 months
2
Phase 1a and 1b: Duration of Response (DOR)
DOR is defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.
Time frame
Up to approximately 60 months
3
Phase 1a and 1b: Time to Response (TTR)
TTR is defined as the time from the date of the first dose of study drugs to the date of the first determination of objective response by the investigator using RECIST v1.1.
Time frame
Up to approximately 60 months
4
Phase 1b: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease assessed by the investigator using RECIST v1.1.
Time frame
Up to approximately 60 months
Other outcomes
Sponsors and contacts
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