Phase 1a/1b First-in-Human Study of BG-C9074 Alone and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors

Phase 1RecruitingNCT06233942

BeOne Medicines308 enrolled

Overview

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 other anticancer therapies in patients with advanced solid tumors.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

308

Conditions

Advanced Solid Tumor

Interventions

BG-C9074DRUG

administered by intravenous infusion

TislelizumabDRUG

administered by intravenous infusion

BevacizumabDRUG

administered by intravenous infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 previously received standard systemic therapy and whose cancer is not amenable to therapy with curative intent, and for whom further treatment is not available or not tolerated. Enrollment will be limited to participants with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer, cholangiocarcinoma (CCA), endometrial cancer, squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), or ovarian cancer. Enrollment in the Japan cohort will be limited to participants with HR+/HER2- breast cancer, TNBC, endometrial cancer, or ovarian cancer. 4. ≥ 1 measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) 5. Able to provide an archived tumor tissue sample. 6. Adequate bone marrow and 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 B7 homolog 4 (B7H4)-targeting antibody-drug conjugate (ADC) or an ADC with a topoisomerase 1 inhibitor (TOP1i) payload. 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 (including intermittent use) 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.

Locations (37)

Outcomes

Primary Outcomes

Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number of participants with AEs and SAEs (as graded by the National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] Version \[v\] 5.0),, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity criteria.

Time frame: 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

Time frame: 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

Time frame: Approximately 18 months

Phase 1b: Overall Response Rate (ORR) as monotherapy and in combination with tislelizumab

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.

Time frame: Approximately 3 years

Phase 1b: Recommended Phase 2 dose (RP2D) of BG-C9074 as monotherapy and in combination with bevacizumab or tislelizumab

The RP2D of BG-C9074 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.

Time frame: Approximately 30 months

Secondary Outcomes

Central Contacts

Study Director

CONTACT

1.877.828.5568 clinicaltrials@beonemed.com

Data from ClinicalTrials.gov

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Usc Norris Comprehensive Cancer Center (Nccc)

Los Angeles, California, United States

RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, United States

RECRUITING

Florida Cancer Specialist Research Institute Lake Nona

Orlando, Florida, United States

RECRUITING

Sidney Kimmel Comprehensive Cancer At Johns Hopkins

Baltimore, Maryland, United States

RECRUITING

James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

RECRUITING

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, Australia

RECRUITING

Macquarie University

North Ryde, New South Wales, Australia

RECRUITING

Cancer Care Wollongong

Wollongong, New South Wales, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

RECRUITING

Monash Health

Clayton, Victoria, Australia

RECRUITING

...and 27 more locations

Phase 1a: ORR as monotherapy and in combination with tislelizumab

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.

Time frame: Approximately 3 years

Phase 1b: ORR as monotherapy and in combination with bevacizumab or tislelizumab

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.

Time frame: Approximately 3 years

Phase 1b: ORR per B7-H4 (B7 homolog 4) protein expression

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 and evaluated according to the amount of B7-H4 (B7 homolog 4) protein expressed in their tumors

Time frame: Approximately 3 years

Duration of Response (DOR)

Duration of response (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

Time frame: Approximately 3 years

Duration of Response (DOR) per B7-H4 protein expression

Time frame: 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, as assessed by the investigator

Time frame: Approximately 3 years

Disease Control Rate (DCR) per B7-H4 protein expression

DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease, as assessed by the investigator, and evaluated according to the amount of B7-H4 protein expressed in the tumors

Time frame: 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.

Time frame: Approximately 3 years

Clinical Benefit Rate (CBR) per B7-H4 protein expression

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 investigato, and evaluated according to the amount of B7-H4 protein expressed in the tumors

Time frame: Approximately 3 years

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.

Time frame: 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), and laboratory assessments.

Time frame: Approximately 3 years

Maximum observed plasma concentration (Cmax) for BG-C9074

Time frame: Twice in the first four months

Minimum observed plasma concentration (Cmin) for BG-C9074

Time frame: Approximately 3 years

Time to reach maximum observed plasma concentration (Tmax) for BG-C9074

Time frame: Twice in the first four months

Half-life (t1/2) for BG-C9074

Time frame: Twice in the first four months

Area under the concentration-time curve (AUC) for BG-C9074

Time frame: Twice in the first four months

Apparent clearance (CL/F) for BG-C9074

Time frame: Twice in the first four months

Apparent volume of distribution (Vz/F) for BG-C9074

Time frame: Twice in the first four months

Accumulation ratio for BG-C9074

Time frame: Twice in the first four months

Plasma concentrations for BG-C9074

Time frame: Approximately 3 years

Phase 1a: Number of participants with anti-drug antibodies (ADAs) to BG-C9074 and tislelizumab

Time frame: Approximately 3 years

Phase 1b: Number of participants with anti-drug antibodies (ADAs) to BG-C9074

Time frame: Approximately 3 years

Serum concentration of BG-C0974

Time frame: Approximately 3 years

Serum concentration of Tislelizumab

Time frame: Approximately 3 years