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

BeOne Medicines

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Bevacizumab; Drug: Tislelizumab; Drug: BG-C9074

Study type: Interventional

Funder types: Industry

Identifiers

NCT06233942

BG-C9074-101

Details and patient eligibility

About

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.

Enrollment: 308 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

308 participants in 7 patient groups

Phase 1a: Part A (Monotherapy Dose Escalation)

Experimental group

Description:

BG-C9074 monotherapy dose escalation

Treatment:

Drug: BG-C9074

Phase 1a: Part B (Monotherapy Safety Expansion)

Experimental group

Description:

BG-C9074 dose levels that have been determined to be safe and tolerable in Part A will be investigated.

Treatment:

Drug: BG-C9074

Phase 1a: Part C (Combination Therapy Dose Escalation)

Experimental group

Description:

BG-C9074 plus tislelizumab combination at the recommended dose for expansion (RDFE).

Treatment:

Drug: BG-C9074

Drug: Tislelizumab

Phase 1a: Part D (Japan Cohort)

Experimental group

Description:

A separate cohort in Japan will evaluate the safety of BG-C9074 monotherapy in Japanese participants with select solid tumors

Treatment:

Drug: BG-C9074

Phase 1b: Monotherapy Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: BG-C9074

Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus tislelizumab)

Experimental group

Description:

This arm will assess BG-C9074 plus tislelizumab as first-line therapy in select solid tumors after completion of the dose escalation phase.

Treatment:

Drug: BG-C9074

Drug: Tislelizumab

Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus bevacizumab)

Experimental group

Description:

This arm will assess BG-C9074 plus bevacizumab in select solid tumors participants after establishing the recommended monotherapy dose and schedule.

Treatment:

Drug: BG-C9074

Drug: Bevacizumab