Study Investigating BGB-24714 as Monotherapy and With Combination Therapies in Participants With Solid Tumors

Solid Tumor, Adult Clinical Trial

Official title:

A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of Second Mitochondrial-derived Activator of Caspases Mimetic BGB-24714 as Monotherapy and With Combination Therapies in Patients With Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05381909
• Other study ID #: BGB-24714-101
• Secondary ID: CTR20232532
• Status: Recruiting
• Phase: Phase 1
• Start date: July 6, 2022
• Est. completion date: November 2026

Study information

• Verified date: March 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: 1-877-828-5568
• Email: ClinicalTrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to understand how safe and well-tolerated a drug called BGB-24714 is when used alone, or in combination with chemotherapy or radiation therapy, for people with advanced or spreading solid tumors. The main objective is to identify the highest tolerable dose or the highest administered dose of BGB-24714. Additionally, the study aims to identify the most suitable doses for further investigation in larger groups of participants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 229
• Est. completion date: November 2026
• Est. primary completion date: October 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Eligibility Criteria :

1. Participants must sign a written informed consent form (ICF); and agree to comply with study requirement

2. Phase 1a (Dose Escalation):

Part A, A-CN, and B: Participants with histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumor previously treated with standard systemic therapy or for whom treatment is not available or not tolerated Note: Only participants in mainland China will be eligible for Part A-CN. Part C: Participant has histologically or cytologically confirmed, locally advanced, unresectable Stage III Non-small cell lung cancer (NSCLC) suitable for definitive chemoradiotherapy (CRT) Part D: Participant with locally advanced, histologically confirmed inoperable esophageal squamous cell carcinoma (ESCC) suitable for definitive CRT Phase 1b (Dose Expansion): Participants with histologically or cytologically confirmed solid tumors of selected types previously treated with standard therapy.

3. Participants must be able to provide formalin-fixed paraffin embedded (FFPE) tumor tissue sample.

4. Phase 1a Part A, A-CN, B and Phase 1b: = 1 measurable lesion per Response evaluation criteria in solid tumors (RECIST) v1.1

5. Eastern Cooperative Oncology Group (ECOG) Performance Status = 1

Key Exclusion Criteria:

1. Active leptomeningeal disease or uncontrolled, untreated brain metastasis.

2. Any malignancy = 3 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent

3. Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication = 14 days before the first dose of study drug(s).

4. Clinically significant infection requiring systemic therapy = 14 days before the first dose of study drug(s).

5. Prior exposure to agents with second mitochondria-derived activator of caspases (SMAC) mimetics, or other Inhibitors of apoptosis proteins (IAPs) antagonists. NOTE: Other protocol defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

Drug:
• BGB-24714
administered orally
• Paclitaxel
administered intravenously
• Carboplatin
administered intravenously
• Docetaxel
administered intravenously

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Austin Health	Heidelberg	Victoria
Australia	Icon Cancer Care South Brisbane	South Brisbane	Queensland
China	Hunan Cancer Hospital	Changsha	Hunan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Shandong Cancer Hospital	Jinan	Shandong
China	Shandong Provincial Hospital	Jinan	Shandong
China	Henan Cancer Hospital	Zhengzhou	Henan
Korea, Republic of	National Cancer Center	Goyangsi	Gyeonggido
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Incheon Gwang'yeogsi
Korea, Republic of	Seoul National University Bundang Hospital	Seongnamsi	Gyeonggido
Korea, Republic of	Asan Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul	Seoul Teugbyeolsi
Korea, Republic of	The Catholic University of Korea, St Vincents Hospital	Suwonsi	Gyeonggido
New Zealand	Auckland City Hospital	Auckland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Texas Md Anderson Cancer Center (Department Gi Medical Oncology)	Houston	Texas
United States	Tennessee Oncology, Pllc Nashville	Nashville	Tennessee
United States	Florida Cancer Specialist (Scri) Sarasota	Sarasota	Florida
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia,  China,  Korea, Republic of,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: Number of participants with adverse events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs ), and experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria.	approximately 6 months
Primary	Dose Escalation: Maximum tolerated dose (MTD) of BGB-24714 as monotherapy, in combination with chemotherapy, and in combination with concurrent chemoradiotherapy (cCRT)		approximately 6 months
Primary	Dose Escalation: Recommended Doses for Expansion (RDFE) of BGB-24714 as monotherapy, in combination with chemotherapy, and in combination with concurrent chemoradiotherapy (cCRT)	Recommended dose based upon the MTD or MAD, as well as the long-term tolerability, pharmacokinetics, efficacy, and any other relevant data as available	approximately 6 months
Primary	Dose Expansion: Objective response rate (ORR)	ORR is defined as the percentage of participants with partial or complete response, as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	approximately 2 Years
Secondary	Dose Escalation: Objective response rate (ORR)	ORR is defined as the percentage of participants with partial or complete response, as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	approximately 2 Years
Secondary	Dose Expansion: Progression-free Survival (PFS)	PFS is defined as the time from the date of the first dose of study drug to the date of first documentation of disease progression as determined by the investigator using RECIST v1.1 or death, whichever occurs first	approximately 2 Years
Secondary	Dose Expansion: Number of participants with adverse events	Number of participants with AEs and SAEs	approximately 2 Years
Secondary	Duration of Response (DOR)	DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	approximately 2 Years
Secondary	Disease Control Rate (DCR)	DCR is defined as the percentage of participants whose best overall response is complete response, partial response, or stable disease, as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	approximately 2 Years
Secondary	Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants who have complete response, partial response, and stable disease, as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	approximately 2 Years
Secondary	Plasma Concentrations of BGB-24714 and its metabolite		approximately 2 Years
Secondary	Maximum Observed Plasma Concentration (Cmax) of BGB-24714 and its metabolite		Up to 48 hours postdose
Secondary	Time to Maximum Plasma Concentration (Tmax) of BGB-24714 and its metabolite		Up to 48 hours postdose
Secondary	Terminal Half-life (t1/2) of BGB-24714 and its metabolite		Up to 48 hours postdose
Secondary	Area Under the Plasma Concentration Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-24714 and its metabolite		Up to 48 hours postdose
Secondary	Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) of BGB-24714 and its metabolite		Up to 48 hours postdose
Secondary	Apparent Clearance (CL/F) of BGB-24714		Up to 48 hours postdose
Secondary	Apparent Volume Of Distribution (Vz/F) of BGB-24714		Up to 48 hours postdose
Secondary	Concentration at steady state (Cmax,ss) of BGB-24714 and its metabolite		Up to 48 hours postdose
Secondary	Time to Maximum Plasma Concentration at steady state (Tmax,ss) of BGB-24714 and its metabolite		Up to 48 hours postdose
Secondary	Area Under the Plasma Concentration Time Curve from Time 0 to the Last Quantifiable Concentration at Steady State (AUClast,ss) of BGB-24714 and its metabolite		Up to 48 hours postdose
Secondary	Rough Concentration At Steady State (Ctrough,ss) of BGB-24714 and its metabolite		Up to 48 hours postdose