## Protocol Section
### Identification Module
**NCT ID:** NCT06427941

**Brief Title:** A Phase 1 Study of BGB-B2033, Alone or in Combination With Tislelizumab, 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 BGB-B2033, Alone or in Combination With Tislelizumab, in Participants With Selected Advanced or Metastatic Solid Tumors

#### Organization Study ID Info
**ID:** BGB-B2033-101
#### Organization
**Class:** INDUSTRY
**Full Name:** BeiGene
### Status Module
#### Completion Date
**Date:** 2026-10-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-10-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-23

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-20
**Study First Submit QC Date:** 2024-05-20
### 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 study is a first-in-human (FIH) Phase 1 study of BGB-B2033 to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of the BGB-B2033 in participants with advanced or metastatic hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP)-producing gastric cancer (GC), extragonadal yolk sac tumors, non-dysgerminomas, or glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC). The study will also identify the recommended Phase 2 dose (RP2D) of BGB-B2033 alone and in combination with tislelizumab for subsequent proof-of-concept studies. BGB-B2033 will be administered by intravenous infusion. The Phase 1 study will be conducted in 2 parts: Part A (Monotherapy Dose Escalation and Safety Expansion) and Part B (Combination Dose Escalation and Safety Expansion).

### Conditions Module

**Conditions:**

- Metastatic Hepatocellular Carcinoma

- Advanced Hepatocellular Carcinoma

- Alpha-fetoprotein (AFP)-Producing Gastric Cancer

- Extragonadal Yolk Sac Tumors

- Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer

- Metastatic Solid Tumor

**Keywords:**

- HCC

- GC

- GPC-3

- GPC3-positive squamous non-small cell lung cancer

- NSCLC

- BGB-B2033

- tislelizumab

- metastatic hepatocellular carcinoma

- Advanced Hepatocellular Carcinoma

- alpha-fetoprotein (AFP)-producing gastric cancer

- extragonadal yolk sac tumors

- Squamous Non-small-cell Lung Cancer

- Non-dysgerminomas squamous non-small cell lung cancer

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 140

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Ascending dose levels of BGB-B2033 monotherapy will be sequentially enrolled to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and initial anti-tumor effects

**Intervention Names:**

- Drug: BGB-B2033

**Label:** Part A (Monotherapy Dose Escalation and Safety Expansion)

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Cohorts of BGB-B2033 in combination with tislelizumab will be sequentially enrolled to evaluate the safety, tolerability, PK, pharmacodynamics, and initial anti-tumor effects of this combination

**Intervention Names:**

- Drug: BGB-B2033

- Drug: Tislelizumab

**Label:** Part B (Combination Dose Escalation and Safety Expansion)

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Part A (Monotherapy Dose Escalation and Safety Expansion)

- Part B (Combination Dose Escalation and Safety Expansion)

**Description:** Administered by intravenous infusion

**Name:** BGB-B2033

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Part B (Combination Dose Escalation and Safety 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/American Society for Transplantation and Cellular Therapy \[ASTCT\] for cytokine release syndrome \[CRS\] and immune effector cell-associated neurotoxicity syndrome \[ICANS\]), timing, seriousness, and relationship to study therapy; assessment of adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria;

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

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

**Description:** The MTD or MAD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to a target toxicity rate of 30% or the highest dose administered, respectively.

**Measure:** Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033

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

**Description:** The RP2D(s) will be determined based on a biologically effective dose by taking the totality of available preclinical and clinical data, including safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity, into consideration

**Measure:** Recommended Phase 2 dose (RP2D) of BGB-B2033 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 Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

**Measure:** Overall Response Rate (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.

**Measure:** Progression Free Survival (PFS)

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

**Measure:** Serum concentration of BGB-B2033

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

**Measure:** Number of participants with anti-drug antibodies (ADAs) to BGB-B2033

**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. Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place, whichever is older).
3. Participants with any of the following unresectable locally advanced or metastatic tumor types:

   1. HCC
   2. Histologically confirmed AFP-producing GC (serum AFP \> 20 ng/mL or tumor tissue AFP positive by a validated IHC assay according to local testing criteria)
   3. Histologically confirmed germ cell tumor including extragonadal yolk sac tumors located in mediastinum, vagina, brain, and retroperitoneum, etc) and non-dysgerminomas
   4. Histologically confirmed GPC3-positive squamous NSCLC
4. ≥ 1 evaluable lesion for dose escalation and ≥ 1 measurable lesion for safety expansion, per RECIST v1.1
5. ECOG Performance Status score ≤ 1

Exclusion Criteria:

1. Prior therapy targeting glypican-3 (GPC3) or the T-cell costimulatory receptor 4-1BB (also known as CD137)
2. Active leptomeningeal disease or uncontrolled, untreated brain metastasis
3. Active autoimmune diseases or history of autoimmune diseases that may relapse
4. Any malignancy ≤ 2 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
5. Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug(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 - Ancestors

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000012142

- Term: Respiratory Tract Neoplasms

- ID: D000013899

- Term: Thoracic Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000002283

- Term: Carcinoma, Bronchogenic

- ID: D000001984

- Term: Bronchial Neoplasms

- ID: D000000230

- Term: Adenocarcinoma

- ID: D000008113

- Term: Liver Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000008107

- Term: Liver Diseases

- ID: D000005770

- Term: Gastrointestinal Neoplasms

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000013272

- Term: Stomach Diseases

- ID: D000008649

- Term: Mesonephroma

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M5546

- Name: Carcinoma, Non-Small-Cell Lung

- Relevance: HIGH

- As Found: Non-Small Cell Lung Cancer

- ID: M16064

- Name: Stomach Neoplasms

- Relevance: HIGH

- As Found: Gastric Cancer

- ID: M5534

- Name: Carcinoma

- Relevance: HIGH

- As Found: Carcinoma

- ID: M11172

- Name: Lung Neoplasms

- Relevance: HIGH

- As Found: Lung Cancer

- ID: M9613

- Name: Carcinoma, Hepatocellular

- Relevance: HIGH

- As Found: Hepatocellular Carcinoma

- ID: M20386

- Name: Endodermal Sinus Tumor

- Relevance: HIGH

- As Found: Yolk sac tumor

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M14979

- Name: Respiratory Tract Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16658

- Name: Thoracic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5540

- Name: Carcinoma, Bronchogenic

- Relevance: LOW

- As Found: Unknown

- ID: M5260

- Name: Bronchial Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M3585

- Name: Adenocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M11113

- Name: Liver Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11107

- Name: Liver Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M16062

- Name: Stomach Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: T5486

- Name: Stomach Cancer

- Relevance: LOW

- As Found: Unknown

- ID: T5605

- Name: Testicular Yolk Sac Tumor

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000002277

- Term: Carcinoma

- ID: D000009369

- Term: Neoplasms

- ID: D000008175

- Term: Lung Neoplasms

- ID: D000002289

- Term: Carcinoma, Non-Small-Cell Lung

- ID: D000006528

- Term: Carcinoma, Hepatocellular

- ID: D000013274

- Term: Stomach Neoplasms

- ID: D000018240

- Term: Endodermal Sinus Tumor

### Intervention Browse Module - Ancestors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M137899

- Name: Tislelizumab

- Relevance: HIGH

- As Found: Meet

- 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
