Clinical trial NCT05904496: A Study of BGB-30813 Alone or in Combination With Tislelizumab in Participants With Advanced or Metastatic Solid Tumors
Official title: A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of the DGKζ Inhibitor BGB-30813, Alone or in Combination With the Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: DGKζ Inhibitor
BGB-30813
Anti-PD-1 Monoclonal Antibody
Tislelizumab
Advanced or Metastatic Solid Tumors
Diacylglycerol kinase
BGB-A317
NSCLC
Immunotherapy
HNSCC
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2023-06-15
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a First in Human (FIH) Phase 1, multicenter, open label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-30813 as monotherapy or in combination with tislelizumab in participants with advanced or metastatic solid tumors. The study will be conducted in 2 parts: Phase 1a dose escalation and Phase 1b dose expansion.

Detailed description: This study will test whether taking BGB-30813 alone or with tislelizumab can help treat patients with cancer that has spread throughout the body or is locally advanced. The two main goals of the study are to ensure that the treatments are safe by monitoring side effects and to determine the number of participants who respond well to treatment either partially or completely. The combination of BGB-30813 with other drugs that target immune checkpoints may work together to stop or prevent cancer activity.

Approximately 200 participants will participate. In the first part of the study, participants will be given different doses of BGB-30813 either alone or with tislelizumab to find the dose that is best tolerated. BGB-30813 will be given orally and tislelizumab will be given through a vein. In the second part of the study, the selected dose of BGB-30813, either alone or with tislelizumab, will be given to a larger number of participants from different parts of the world to see if the treatments can improve the signs and symptoms of their cancer. Treatments will continue until participants are no longer considered to be receiving benefits, have unacceptable side effects, or withdraw consent.

Eligibility criteria: Inclusion Criteria:

* Phase 1a (Dose Escalation):

  * Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have previously received available standard systemic therapy or for whom treatment is not available or not tolerated and who have not received any prior therapy targeting diacylglycerol kinase (DGK)
  * Eligible tumor types are immune sensitive solid tumors such as non-small cell lung cancer (NSCLC), head neck squamous cell cancer (HNSCC), small cell lung cancer, hepatocellular carcinoma, esophageal cancer, gastric or gastroesophageal carcinoma, nasopharyngeal carcinoma, triple-negative breast cancer, urothelial carcinoma, renal cell carcinoma, cervical cancer, endometrial carcinoma, cutaneous squamous cell carcinoma, melanoma, Merkel cell carcinoma, mesothelioma, microsatellite instability (MSI)-high, tumor mutation burden (TMB)-high, or mismatch repair deficient solid tumors
  * Prior checkpoint inhibitor (CPI) therapy is allowed
* Phase 1b (Dose Expansion):

  * Participants with selected advanced or metastatic solid tumors including NSCLC, HNSCC, and additional potential tumor types to be defined based on emerging data
* ≥ 1 measurable lesion per RECIST v1.1
* Eastern Cooperative Group Oncology Performance (ECOG) Performance Status score ≤ 1
* Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study
* Adequate organ function as indicated by the following laboratory values up to first dose of study treatment: Hemoglobin≥ 90 grams per liter (g/L), Absolute neutrophil count ≥ 1.5 x 109/L , Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (\< 3 x ULN for participants with Gilbert syndrome ), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN

Exclusion Criteria:

* Previous therapy targeting DGK
* Active leptomeningeal disease or uncontrolled symptomatic central nervous system (CNS) metastasis
* Active autoimmune diseases or history of autoimmune diseases that may relapse
* Any active malignancy ≤ 2 years before the first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent
* Systemic anticancer therapy, including chemotherapy ≤ 21 days or 5 half-lives (whichever is shorter) before the first dose of study drugs
* ≥ Grade 3 immune-mediated adverse events on prior immuno-oncology agent (anti-PD-1 or anti-CTLA4 antibodies or other experimental drugs)

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

Primary outcomes:
measure: Phase 1a: Dose Escalation: Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Dose-Limiting Toxicities (DLTs)
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; approximately 6 months
measure: Phase 1a: Dose Escalation: The Maximum Tolerated Dose (MTD) and Maximum Administered Dose (MAD)
timeFrame: Up to approximately 6 months
measure: Phase 1a and 1b: Recommended dose(s) for Expansion (RDFE[s]) of BGB-30813 Alone or in Combination with Tislelizumab
timeFrame: Up to approximately 6 months
measure: Phase 1b: Dose Expansion: Overall Response Rate (ORR) as Determined by the Investigator
timeFrame: Up to approximately 12 months
Secondary outcomes:
measure: Phase 1a: Dose Escalation: ORR as Determined by the Investigator
timeFrame: Up to approximately 12 months
measure: Phase 1a: Dose Escalation: Maximum Observed Plasma Concentration (Cmax) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab
timeFrame: Up to approximately 6 months
measure: Phase 1a: Dose Escalation: Observed Plasma Trough Concentration (Ctrough) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab
timeFrame: Up to approximately 6 months
measure: Phase 1a: Dose Escalation: Area under the concentration-time curve (AUC) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab
timeFrame: Up to approximately 6 months
measure: Phase 1a: Dose Escalation: Half-life (t1/2) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab
timeFrame: Up to approximately 6 months
measure: Phase 1b: Dose Expansion: Number of Participants Experiencing AEs and SAEs
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months
measure: Phase 1b: Dose Expansion: Duration of Response (DOR)
timeFrame: Up to approximately 12 months
measure: Phase 1b: Dose Expansion: Disease Control Rate (DCR)
timeFrame: Up to approximately 12 months
measure: Phase 1b: Dose Expansion: Progression Free Survival (PFS)
timeFrame: Up to approximately 12 months
measure: Phase 1b: Dose Expansion: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 12 months
measure: Phase 1b: Dose Expansion: Plasma concentrations of BGB-30813, and its metabolite, BGB-33481
timeFrame: Up to approximately 6 months
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Madrid
country: Spain
facility: Start Madrid Fundacion Jimenez Diaz
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: