Study of BG-C9074 as Monotherapy and in Combination With Tislelizumab in Participants With Advanced Solid Tumors

Phase 1a/1b Study of BG-C9074, an Antibody Drug Conjugate Targeting B7H4, as Monotherapy and in Combination With Tislelizumab in Participants With Advanced Solid Tumors

This is a first-in-human, dose finding and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-C9074 alone and in combination with tislelizumab in participants with advanced solid tumors. Participants will receive study drug(s) until progressive disease, unacceptable toxicity, withdrawal of consent, death, or another discontinuation criterion is met, whichever occurs first. The maximum length of receiving study drug(s) for a participant is up to 2 years.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Tislelizumab; Drug: BG-C9074

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 1.877.828.5568; Email: clinicaltrials@beigene.com

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia, 2500
      • Recruiting
      • Cancer Care Wollongong
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
3. Participants with selected histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have been previously treated.
4. ≥ 1 measurable lesion per RECIST v1.1.
5. Able to provide an archived tumor tissue sample.
6. Adequate organ function.
7. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for ≥ 7 months after the last dose of study drug(s).
8. Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study treatment period and for ≥ 4 months after the last dose of study drug(s).

Exclusion Criteria:

1. Prior treatment with a B7H4-targeting antibody drug conjugates (ADC)
2. Active leptomeningeal disease or uncontrolled, untreated brain metastasis
3. Any malignancy ≤ 2 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).
4. History of interstitial lung disease, ≥ Grade 2 noninfectious pneumonitis, oxygen saturation at rest < 92%, or requirement for supplemental oxygen at baseline
5. Uncontrolled diabetes.
6. Infection (including tuberculosis infection) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before the first dose of study treatment(s).

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a: Part A (Monotherapy Dose Escalation); BG-C9074 monotherapy dose escalation	Drug: BG-C9074; administered by intravenous infusion
Experimental: Phase 1a: Part B (Monotherapy Safety Expansion); BG-C9074 dose levels that have been determined to be safe and tolerable in Part A will be investigated.	Drug: BG-C9074; administered by intravenous infusion
Experimental: Phase 1a: Part C (Combination Therapy Dose Escalation); BG-C9074 plus tislelizumab combination at the recommended dose for expansion (RDFE).	Drug: Tislelizumab; administered by intravenous infusion; Drug: BG-C9074; administered by intravenous infusion
Experimental: Phase 1b: Monotherapy Dose Expansion; The monotherapy dose expansion phase will begin once the BG-C9074 monotherapy RDFE and dosing schedule have been determined from Parts A and B in Phase 1a.	Drug: BG-C9074; administered by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 criteria.	Approximately 3 years
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C9074	defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 28% or the highest dose administered, respectively	Approximately 18 months
Phase 1a: Recommended Dose for Expansion (RDFE) of BG-C9074.	The potential RDFE(s) of BG-C9074 alone and in combination with tislelizumab will be determined based on the MTD or MAD, taking into consideration the long-term tolerability, PK, pharmacodynamics, preliminary antitumor activity, and any other relevant data, as available	Approximately 18 months
Phase 1b: Overall Response Rate (ORR)	ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) assessed by the investigator using RECIST v1.1.	Approximately 3 years
Phase 1b: Recommended Phase 2 dose (RP2D) of BG-C9074	The RP2D of BG-C9074 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.	Approximately 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Progression Free Survival (PFS)	PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first.	Approximately 3 years
Phase 1a: ORR	ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) assessed by the investigator using RECIST v1.1.	Approximately 3 years
Duration of Response (DOR)	DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.	Approximately 3 years
Disease Control Rate (DCR)	DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease.	Approximately 3 years
Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks as assessed by investigator.	Approximately 3 years
Phase 1b: Number of Participants with AEs and 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 criteria.	Approximately 3 years
Maximum observed plasma concentration (Cmax) for BG-C9074		Approximately 3 years
Minimum observed plasma concentration (Cmin) for BG-C9074		Approximately 3 years
Time to maximum plasma concentration (Tmax) for BG-C9074		Approximately 3 years
Half-life (t1/2) for BG-C9074		Approximately 3 years
Area under the concentration-time curve (AUC) for BG-C9074		Approximately 3 years
Apparent clearance (CL/F) for BG-C9074		Approximately 3 years
Apparent volume of distribution (Vz/F) for BG-C9074		Approximately 3 years
Accumulation ratio for BG-C9074		Approximately 3 years
Plasma concentrations for BG-C9074		Approximately 3 years
Number of participants with anti-drug antibodies (ADAs) to BG-C9074		Approximately 3 years
Serum concentration of BG-C0974		Approximately 3 years

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2024
• Primary Completion (Estimated): September 28, 2027
• Study Completion (Estimated): September 28, 2027

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Estimated): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; first-in-human; Tislelizumab; BG-C9074; B7H4
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: BG-C9074-101; 2023-509958-65-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No