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

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: BGB-24714; Drug: Paclitaxel; Drug: Docetaxel; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Frenchs Forest, New South Wales, Australia, NSW 2086
      • Northern Beaches Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, QLD 4101
      • Icon Cancer Centre South Brisbane
    • Woolloongabba, Queensland, Australia, QLD 4102
      • Princess Alexandra Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, VIC 3084
      • Austin Health
    • Melbourne, Victoria, Australia, VIC 3000
      • Peter MacCallum Cancer Centre
    • St Albans, Victoria, Australia, VIC 3021
      • Sunshine Hospital
• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Chongqing Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Shandong
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
• South Korea
  • Gyeonggi-do
    • IlsandongGu GoyangSi, Gyeonggi-do, South Korea, 10408
      • National Cancer Center (Korea)
  • Incheon Gwang'yeogsi
    • NamdongGu, Incheon Gwang'yeogsi, South Korea, 21565
      • Gachon University Gil Medical Center
  • Seoul Teugbyeolsi
    • GangnamGu, Seoul Teugbyeolsi, South Korea, 06351
      • Samsung Medical Center
    • SeodaemunGu, Seoul Teugbyeolsi, South Korea, 03722
      • Severance Hospital Yonsei University Health System
    • SongpaGu, Seoul Teugbyeolsi, South Korea, 05505
      • Asan Medical Center
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234-2165
      • Banner MD Anderson Cancer Center
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialist (Scri) Sarasota
    • St. Petersburg, Florida, United States, 33705-1449
      • SCRI Florida Cancer Specialists North
    • West Palm Beach, Florida, United States, 33401-3406
      • Scri Florida Cancer Specialist East
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201-2013
      • Barbara Ann Karmanos Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-1915
      • Hackensack University Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232-1309
      • Upmc Hillman Cancer Center(Univ of Pittsburgh)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105-2108
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57104-4663
      • Sanford Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, Pllc Nashville
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Dallas, Texas, United States, 75390-7208
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030-4000
      • The University of Texas Md Anderson Cancer Center (Department Gi Medical Oncology)
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • Intermountain Healthcare
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Virginia
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Chinese participants 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a: Dose Escalation Part A; Participants will receive escalating doses of BGB-24714 as monotherapy	Drug: BGB-24714; administered orally
Experimental: Phase 1a: Dose Escalation Part D; Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation	Drug: BGB-24714; administered orally; Drug: Paclitaxel; administered intravenously; Drug: Carboplatin; administered intravenously
Experimental: Phase 1a: Dose Escalation Part C; Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation	Drug: BGB-24714; administered orally; Drug: Paclitaxel; administered intravenously; Drug: Carboplatin; administered intravenously
Experimental: Phase 1a: Dose Escalation Part B; Participants will receive increasing dose levels of BGB-24714 in combination with paclitaxel	Drug: BGB-24714; administered orally; Drug: Paclitaxel; administered intravenously
Experimental: Phase 1b: Dose Expansion; BGB 24714 will be administered in combination with paclitaxel or docetaxel in participants with selected solid tumors.	Drug: BGB-24714; administered orally; Drug: Paclitaxel; administered intravenously; Drug: Docetaxel; administered intravenously
Experimental: Phase 1a: Dose Escalation Part A-CN; Participants will receive escalating doses of BGB-24714 as monotherapy in Chinese participants	Drug: BGB-24714; administered orally
Experimental: Phase 1a: Dose Escalation Part E; Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation in Chinese participants	Drug: BGB-24714; administered orally; Drug: Paclitaxel; administered intravenously; Drug: Carboplatin; administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Dose Expansion: Number of participants with adverse events	Number of participants with AEs and SAEs	approximately 2 Years
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
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
Maximum Observed Plasma Concentration (Cmax) of BGB-24714 and its metabolite		Up to 48 hours postdose
Time to Maximum Plasma Concentration (Tmax) of BGB-24714 and its metabolite		Up to 48 hours postdose
Terminal Half-life (t1/2) of BGB-24714 and its metabolite		Up to 48 hours postdose
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
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
Apparent Clearance (CL/F) of BGB-24714		Up to 48 hours postdose
Apparent Volume Of Distribution (Vz/F) of BGB-24714		Up to 48 hours postdose
Concentration at steady state (Cmax,ss) of BGB-24714 and its metabolite		Up to 48 hours postdose
Time to Maximum Plasma Concentration at steady state (Tmax,ss) of BGB-24714 and its metabolite		Up to 48 hours postdose
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
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
Plasma Concentrations of BGB-24714 and its metabolite		approximately 2 Years
Rough Concentration At Steady State (Ctrough,ss) of BGB-24714 and its metabolite		Up to 48 hours postdose

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2022
• Primary Completion (Actual): July 25, 2025
• Study Completion (Actual): July 25, 2025

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Solid tumors; Advanced Solid Tumors; Metastatic Solid Tumors
• Additional Relevant MeSH Terms: Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; Carboplatin; Paclitaxel
• Other Study ID Numbers: BGB-24714-101; CTR20232532 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No