Clinical trial NCT06427941: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-05-24
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 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).


Eligibility criteria: Inclusion Criteria:

1. Participants with any of the following unresectable locally advanced or metastatic tumor types:

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

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).
6. Certain comorbidities in the lung, heart, bleeding condition and infections.

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

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 2 years
measure: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033
timeFrame: Up to approximately 2 years
measure: Recommended Phase 2 dose (RP2D) of BGB-B2033 alone and in combination with tislelizumab
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Serum concentration of BGB-B2033
timeFrame: Up to approximately 2 years
measure: Number of participants with anti-drug antibodies (ADAs) to BGB-B2033
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Mskcc
state: New York
city: Nashville
country: United States
facility: Scri Oncology Partners
state: Tennessee
city: Puyallup
country: United States
facility: Upmc Hillman Cancer Center
state: Washington
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: BundangGu SeongnamSi
country: Korea, Republic of
facility: Cha Bundang Medical Center, Cha University
state: Gyeonggi-do
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: