Study Investigating BGB-24714 as Monotherapy and in Combination With Chemotherapy in Participants With Advanced or Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT05381909
• Recruitment Status: Recruiting
• First Posted: May 19, 2022
• Last Update Posted: February 8, 2023
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: May 16, 2022
• First Posted Date: May 19, 2022
• Last Update Posted Date: February 8, 2023
• Actual Study Start Date: July 6, 2022
• Estimated Primary Completion Date: July 26, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 16, 2022)

• Dose Escalation: Number of participants with adverse events (AEs) [ Time Frame: approximately 6 months ]
  Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs ), and experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria.
• Dose Escalation: Maximum tolerated dose (MTD) of BGB-24714 as monotherapy and in combination with chemotherapy [ Time Frame: approximately 6 months ]
  The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate.
• Dose Escalation: Recommended Phase 2 dose (RP2D) of BGB-24714 as monotherapy and in combination with chemotherapy [ Time Frame: approximately 6 months ]
  Recommended dose based upon the MTD, as well as the long-term tolerability, pharmacokinetics, efficacy, and any other relevant data as available
• Dose Expansion: Objective response rate (ORR) [ Time Frame: approximately 2 Years ]
  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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 16, 2022)

• Dose Escalation: Objective response rate (ORR) [ Time Frame: approximately 2 Years ]
  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)
• Dose Expansion: Progression-free Survival (PFS) [ Time Frame: approximately 2 Years ]
  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
• Dose Expansion: Number of participants with adverse events [ Time Frame: approximately 2 Years ]
  Number of participants with AEs and SAEs
• Duration of Response (DOR) [ Time Frame: approximately 2 Years ]
  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)
• Disease Control Rate (DCR) [ Time Frame: approximately 2 Years ]
  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)
• Plasma concentration of BGB-24714 [ Time Frame: approximately 2 Years ]
• Plasma Concentrations of BGB-24714 metabolite [ Time Frame: approximately 2 Years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Investigating BGB-24714 as Monotherapy and in Combination With Chemotherapy in Participants With Advanced or Metastatic 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 in Combination With Chemotherapy in Patients With Advanced or Metastatic Solid Tumors
• Brief Summary: This is an open-label, multicenter, and non-randomized Phase 1a/1b clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BGB-24714 as monotherapy and in combination with chemotherapy in participants with advanced or metastatic solid tumors.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor, Adult

Intervention

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

Study Arms

• Experimental: Phase 1a: Dose Escalation Part A
  Participants will receive escalating doses of BGB-24714 as monotherapy
  Intervention: Drug: BGB-24714
• Experimental: Phase 1a: Dose Escalation Part B
  Participants will receive increasing dose levels of BGB-24714 in combination with chemotherapy
  Interventions:

  • Drug: BGB-24714
  • Drug: Paclitaxel
• Experimental: Phase 1b: (Dose Expansion)
  Participants will receive the recommended phase 2 dose (RP2D) of BGB-24714 monotherapy or in combination with chemotherapy as determined from Phase 1a
  Interventions:

  • Drug: BGB-24714
  • Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 16, 2022): 244
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 22, 2025
• Estimated Primary Completion Date: July 26, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Eligibility Criteria:

1. Patient must sign a written informed consent form (ICF); and agree to comply with study requirement.
2. Phase 1a (Dose Escalation): Patients 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.
3. Patients must be able to provide an archived formalin-fixed paraffin embedded (FFPE) tumor tissue sample. If archival tissue is not available, fresh tumor biopsy is mandatory.
4. ≥ 1 measurable lesion per RECIST v1.1
5. ECOG Performance Status ≤ 1
6. Patient with adequate organ function

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. Any major surgical procedure ≤ 28 days before the first dose of study drug(s).
6. Prior exposure to agents with Smac mimetics, or other IAP antagonists.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BeiGene; 1-877-828-5568; ClinicalTrials@beigene.com

• Listed Location Countries: Australia, New Zealand, United States

Administrative Information

• NCT Number: NCT05381909
• Other Study ID Numbers: BGB-24714-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: BeiGene
• Original Responsible Party: Same as current
• Current Study Sponsor: BeiGene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: BeiGene
• Verification Date: February 2023