Clinical trial NCT05381909: A Study of BGB-24714 as Monotherapy and With Combination Therapies in Participants With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor, Adult
Keywords: Solid tumors
Advanced Solid Tumors
Metastatic Solid Tumors
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2022-05-19
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose Escalation: Number of participants with adverse events (AEs)
timeFrame: approximately 6 months
measure: Dose Escalation: Maximum tolerated dose (MTD) of BGB-24714 as monotherapy, in combination with chemotherapy, and in combination with concurrent chemoradiotherapy (cCRT)
timeFrame: approximately 6 months
measure: Dose Escalation: Recommended Doses for Expansion (RDFE) of BGB-24714 as monotherapy, in combination with chemotherapy, and in combination with concurrent chemoradiotherapy (cCRT)
timeFrame: approximately 6 months
measure: Dose Expansion: Objective response rate (ORR)
timeFrame: approximately 2 Years
Secondary outcomes:
measure: Dose Escalation: Objective response rate (ORR)
timeFrame: approximately 2 Years
measure: Dose Expansion: Progression-free Survival (PFS)
timeFrame: approximately 2 Years
measure: Dose Expansion: Number of participants with adverse events
timeFrame: approximately 2 Years
measure: Duration of Response (DOR)
timeFrame: approximately 2 Years
measure: Disease Control Rate (DCR)
timeFrame: approximately 2 Years
measure: Clinical Benefit Rate (CBR)
timeFrame: approximately 2 Years
measure: Plasma Concentrations of BGB-24714 and its metabolite
timeFrame: approximately 2 Years
measure: Maximum Observed Plasma Concentration (Cmax) of BGB-24714 and its metabolite
timeFrame: Up to 48 hours postdose
measure: Time to Maximum Plasma Concentration (Tmax) of BGB-24714 and its metabolite
timeFrame: Up to 48 hours postdose
measure: Terminal Half-life (t1/2) of BGB-24714 and its metabolite
timeFrame: Up to 48 hours postdose
measure: Area Under the Plasma Concentration Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-24714 and its metabolite
timeFrame: Up to 48 hours postdose
measure: Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) of BGB-24714 and its metabolite
timeFrame: Up to 48 hours postdose
measure: Apparent Clearance (CL/F) of BGB-24714
timeFrame: Up to 48 hours postdose
measure: Apparent Volume Of Distribution (Vz/F) of BGB-24714
timeFrame: Up to 48 hours postdose
measure: Concentration at steady state (Cmax,ss) of BGB-24714 and its metabolite
timeFrame: Up to 48 hours postdose
measure: Time to Maximum Plasma Concentration at steady state (Tmax,ss) of BGB-24714 and its metabolite
timeFrame: Up to 48 hours postdose
measure: 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
timeFrame: Up to 48 hours postdose
measure: Rough Concentration At Steady State (Ctrough,ss) of BGB-24714 and its metabolite
timeFrame: Up to 48 hours postdose
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner Md Anderson Cancer Center
state: Arizona
city: Saint Petersburg
country: United States
facility: Scri Florida Cancer Specialists North
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialist (Scri) Sarasota
state: Florida
city: West Palm Beach
country: United States
facility: Scri Florida Cancer Specialist East
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Pittsburgh
country: United States
facility: Upmc Hillman Cancer Center(Univ of Pittsburgh)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera Cancer Institue
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Oncology, Pllc Nashville
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Md Anderson Cancer Center (Department Gi Medical Oncology)
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Healthcare
state: Utah
city: Fairfax
country: United States
facility: Next Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Frenchs Forest
country: Australia
facility: Northern Beaches Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Centre South Brisbane
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
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: PaldalGu SuwonSi
country: Korea, Republic of
facility: The Catholic University of Korea, St Vincents Hospital
state: Gyeonggi-do
city: NamdongGu
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Incheon Gwang'yeogsi
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: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
References: