## Protocol Section
### Identification Module
**NCT ID:** NCT06422520

**Brief Title:** Phase 1 First-in-Human Study of BGB-C354 Alone and in Combination With Tislelizumab in Participants With Advanced Solid Tumors

**Official Title:** A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of BGB-C354, an Antibody-Drug Conjugate Targeting B7H3, Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

#### Organization Study ID Info
**ID:** BGB-C354-101
#### Organization
**Class:** INDUSTRY
**Full Name:** BeiGene
#### Secondary ID Infos
**ID:** 2024-513280-11-00
**Type:** CTIS
### Status Module
#### Completion Date
**Date:** 2026-11-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-21

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-11-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-24

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-21
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-15
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** BeiGene

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This is a first-in-human, Phase 1a/1b study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BGB-C354 alone and in combination with tislelizumab in participants with advanced solid tumors.

Study details include:

* The study will be conducted in 2 phases: Phase 1a (Monotherapy Dose Escalation and Safety Expansion) and Phase 1b (Dose Expansion).
* The visit frequency will be approximately every 21 days during study treatment, and higher frequencies may be considered based on emerging data. The maximum treatment duration will be up to 2 years.
* The study duration is estimated to be approximately 5 years.

### Conditions Module

**Conditions:**

- Advanced Solid Tumor

**Keywords:**

- BGB-C354

- Tislelizumab

- First-in-human

- Advanced solid tumor

- Anti-PD-1 Monoclonal Antibody

- B7H3

- antibody drug conjugate

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 62

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** BGB-C354 monotherapy doses at sequentially increasing levels.

**Intervention Names:**

- Drug: BGB-C354

**Label:** Phase 1a: Part A (Monotherapy Dose Escalation)

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants will enroll at safe dose levels recommended by the Safety Monitoring Committee (SMC) for further evaluation.

**Intervention Names:**

- Drug: BGB-C354

**Label:** Phase 1a: Part B (Safety Expansion)

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** The dose expansion phase begins after determining the recommended dose for expansion (RDFE) and schedule from Phase 1a, exploring at least 2 dose levels for optimization.

**Intervention Names:**

- Drug: BGB-C354

**Label:** Phase 1b: Part C (Monotherapy Expansion)

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** BGB-C354 and tislelizumab will start at the RDFE-1 level set by the SMC using Phase 1a data, or at a dose level lower than the highest tolerable level established in Part A.

**Intervention Names:**

- Drug: BGB-C354

- Drug: Tislelizumab

**Label:** Phase 1b: Part D (Combination Therapy Expansion)

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Phase 1a: Part A (Monotherapy Dose Escalation)

- Phase 1a: Part B (Safety Expansion)

- Phase 1b: Part C (Monotherapy Expansion)

- Phase 1b: Part D (Combination Therapy Expansion)

**Description:** Administered by intravenous infusion

**Name:** BGB-C354

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Phase 1b: Part D (Combination Therapy Expansion)

**Description:** Administered by intravenous infusion

**Name:** Tislelizumab

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0\]), timing, seriousness, and relationship to study drug(s); physical examinations; electrocardiograms (ECGs); and laboratory assessments as needed; and adverse events meeting protocol-defined dose-limitingtoxicity (DLT) criteria

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

**Time Frame:** Up to approximately 2 years

**Description:** Defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% or the highest dose administered, respectively

**Measure:** Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-C354

**Time Frame:** Up to approximately 2 years

**Description:** The potential RDFE(s) of BGB-C354 will be determined based on the MTD or MAD, taking into consideration the long-term tolerability, pharmacokinetics (PK), preliminary antitumor activity, and any other relevant data, as available

**Measure:** Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-C354

**Time Frame:** Up to approximately 2 years

**Description:** 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 Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

**Measure:** Phase 1b: Overall Response Rate (ORR)

**Time Frame:** Up to approximately 2 years

**Description:** The RP2D of BGB-C354 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.

**Measure:** Phase 1b: Recommended Phase 2 dose (RP2D) of BGB-C354 alone and in combination with tislelizumab

**Time Frame:** Up to approximately 2 years

#### Secondary Outcomes

**Description:** 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.

**Measure:** Phase 1a: ORR

**Time Frame:** Up to approximately 2 years

**Description:** 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.

**Measure:** Duration of Response (DOR)

**Time Frame:** Up to approximately 2 years

**Description:** DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease as determined from tumor assessments by the investigator using RECIST v1.1.

**Measure:** Disease Control Rate (DCR)

**Time Frame:** Up to approximately 2 years

**Description:** 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.determined from tumor assessments by the investigator using RECIST v1.1.

**Measure:** Phase 1b: Progression Free Survival (PFS)

**Time Frame:** Up to approximately 2 years

**Description:** Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0\]), timing, seriousness, and relationship to study drug(s); physical examinations; electrocardiograms (ECGs); and laboratory assessments as needed; and adverse events meeting protocol-defined dose-limitingtoxicity (DLT) criteria

**Measure:** Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events

**Time Frame:** Up to approximately 2 years

**Measure:** Maximum observed plasma concentration (Cmax) for BGB-C354

**Time Frame:** Up to approximately 2 years

**Measure:** Minimum observed plasma concentration (Cmin) for BGB-C354

**Time Frame:** Up to approximately 2 years

**Measure:** Time to maximum plasma concentration (Tmax) for BGB-C354

**Time Frame:** Up to approximately 2 years

**Measure:** Half-life (t1/2) for BGB-C354

**Time Frame:** Up to approximately 2 years

**Measure:** Area under the concentration-time curve (AUC) for BGB-C354

**Time Frame:** Up to approximately 2 years

**Measure:** Apparent clearance (CL/F) for BGB-C354

**Time Frame:** Up to approximately 2 years

**Measure:** Apparent volume of distribution (Vz/F) for BGB-C354

**Time Frame:** Up to approximately 2 years

**Measure:** Accumulation ratio for BGB-C354

**Time Frame:** Up to approximately 2 years

**Measure:** Number of participants with anti-drug antibodies (ADAs) to BGB-C354

**Time Frame:** Up to approximately 2 years

**Measure:** Serum concentration of BGB-C354

**Time Frame:** Up to approximately 2 years

### Eligibility Module

**Eligibility Criteria:** 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 of 0 or 1.
3. Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose cancer is not amenable to therapy with curative intent:
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 B7H3-targeted therapy.
2. For Part B and Phase 1b: Prior treatment with antibody drug conjugates (ADCs) with topoisomerase I inhibitor payload (for Phase 1b, unless otherwise specified for specific cohorts).
3. Participants with spinal cord compressions, active leptomeningeal disease or uncontrolled, or untreated brain metastasis
4. 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).
5. History of interstitial lung disease, ≥ Grade 2 noninfectious pneumonitis, oxygen saturation at rest \< 92%, or requirement for supplemental oxygen at baseline
6. Uncontrolled diabetes, or \> Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium levels despite standard medical management ≤ 14 days before the first dose of study drug(s).
7. 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** clinicaltrials@beigene.com

**Name:** Study Director

**Phone:** 1.877.828.5568

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** BeiGene

**Name:** Study Director

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** YES

## Derived Section

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

### Intervention Browse Module - Ancestors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ANeo

- Name: Antineoplastic Agents

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M4230

- Name: Antibodies, Monoclonal

- Relevance: LOW

- As Found: Unknown

- ID: M137899

- Name: Tislelizumab

- Relevance: HIGH

- As Found: Meet

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000707970

- Term: Tislelizumab

### Misc Info Module

- Version Holder: 2024-05-31
