Study of BGB-A425 and LBL-007 in Combination With Tislelizumab in Advanced Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Beigene Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Jun 2023 → 7 Feb 2025

Decision date (initial)

2022-10-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BeiGene Ltd.

External identifiers

EU CT number

2022-500694-14-00

WHO UTN

U1111-1278-0027

ClinicalTrials.gov

NCT03744468

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Therapy, Safety

Phase 1 (Dose Escalation):

• To assess the safety and tolerability of BGB-A425 in combination with tislelizumab
in patients with advanced solid tumors
• To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended Phase 2 dose (RP2D) of BGB-A425 in combination with tislelizumab

Phase 2 (Safety Lead-in):

• To assess the safety and tolerability of BGB-A425 in combination with LBL-007 and tislelizumab or LBL-007 in combination with tislelizumab in patients with advanced solid tumors
• To determine the MTD or MAD and RP2D/ recommended dose for expansion of LBL-007 in combination with BGB-A425 and tislelizumab, and LBL-007 in combination with tislelizumab

Phase 2 (Dose Expansion):

• To evaluate antitumor activity based on objective response rate (ORR) of various combinations of BGB-A425 and LBL-007 with tislelizumab in selected tumor types

Secondary objectives 10

1. Phase 1 (Dose Escalation): To assess the preliminary antitumor activity of BGB-A425 in combination with tislelizumab
2. Phase 1 (Dose Escalation): To characterize the pharmacokinetics (PK) of BGB-A425 in combination with tislelizumab
3. Phase 1 (Dose Escalation): To assess host immunogenicity to BGB-A425 in combination with tislelizumab
4. Phase 2 (Safety Lead-in): To assess the preliminary antitumor activity of BGB-A425 in combination with LBL-007 and tislelizumab or the combination of LBL-007 with tislelizumab in patients with advanced solid tumors
5. Phase 2 (Safety Lead-in): To characterize the PK of BGB-A425, LBL-007, and tislelizumab in the combination treatments
6. Phase 2 (Safety Lead-in): To assess host immunogenicity to BGB-A425, LBL-007, and tislelizumab in the combination treatments
7. Phase 2 (Dose Expansion): To evaluate antitumor activity using other secondary efficacy endpoints of the combination treatments of BGB-A425 and LBL-007 with tislelizumab
8. Phase 2 (Dose Expansion): To further characterize the safety and tolerability of various combinations of BGB-A425 and LBL-007 with tislelizumab
9. Phase 2 (Dose Expansion): To further characterize the PK of BGB-A425 and LBL-007 in combination with tislelizumab
10. Phase 2 (Dose Expansion): To further assess host immunogenicity to BGB-A425 and LBL-007 in combination with tislelizumab

Conditions and MedDRA coding

Head and Neck Squamous Cell Cancer

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002480-PIP01-18

Plan to share IPD

Yes

IPD plan description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, and shared when it is feasible to do so without compromising the privacy of study participants. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data along with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
2. Adequate organ function
3. Phase 1 Dose Escalation + Phase 2 Safety Lead-In: Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who have previously received standard systemic therapy or for which treatment is not available or not tolerated
4. Phase 2 Dose-Expansion: Participants with one of the following histologically or cytologically confirmed solid tumors: For HNSCC participants in cohort 1,4 and 6 (PD-L1 positive): Recurrent/metastatic head and neck squamous cell cancer of the oral cavity, oropharynx, hypopharynx, and/or larynx whose tumor is not amenable to local therapy with curative intent (ie, surgery or radiation therapy with or without chemotherapy; For NSCLC participants in Cohort 2, 5 and 7 (PD-L1 positive): Locally recurrent Stage IIIB, stage IIIC or Stage IV squamous or non-squamous non-small cell lung cancer; For RCC participants in Cohort 3: Locally advanced unresectable or metastatic and histologically confirmed renal cell carcinoma with a clear cell histology.

Exclusion criteria 13

1. NSCLC patients with known EGFR mutation, BRAF mutation, ALK fusion, or ROS1 fusion
2. Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
3. Active autoimmune diseases or history of autoimmune diseases that may relapse.
4. Interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases
5. Uncontrolled diabetes or significant cardiac issues
6. Infections requiring systemic antibacterial, antifungal, or antiviral therapy
7. History of severe hypersensitivity reactions to other monoclonal antibodies
8. History of HIV infection or untreated chronic hepatitis B or chronic hepatitis B virus carriers
9. Major surgical procedure within 28 days before study drug administration
10. Chemotherapy, radiotherapy, immunotherapy or any investigational therapies within 28 days (PH 2 Safety Lead-In) or 14 days (PH 2 Dose Expansion) or 5 half-lives of (whichever is shorter) of first administration of study drug(s)
11. With infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 14 days prior to the first dose of study drug(s), or a requirement for chronic prophylactic treatment with antibiotics.
12. Concurrent participation in another therapeutic clinical trial
13. Received prior therapies targeting TIM-3and/or LAG3

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Phase 1(Dose Escalation) & Phase 2(Safety Lead-in): Adverse events (AEs) and serious AE (SAEs) as characterized by type, frequency, severity (as graded by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] Version 5.0), timing, seriousness, and relationship to study therapy; laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing; AEs meeting protocol defined dose limiting toxicity (DLT) criteria
2. Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): The MTD or MAD is defined as the highest dose at which < 33% of the patients experience a DLT
3. Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): The RP2D/recommended dose for expansion of the combination treatments will be determined based upon the MTD or MAD, and will also take into consideration the longterm tolerability, PK, efficacy, and any other relevant data as available
4. Phase 2 (Dose Expansion): ORR as determined from investigator derived tumor assessments per RECIST v1.1

Secondary endpoints 7

1. Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): Efficacy evaluations: ORR, duration of response (DOR), and disease control rate (DCR) will be determined from investigator derived tumor assessments per RECIST v1.1
2. Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): PK: Maximum observed plasma concentration (Cmax), minimum observed plasma concentration (Cmin), time to maximum plasma concentration (Tmax), half-life (t1/2), area under the concentration-time curve from zero to 21 days (AUC0-21d), CL, and apparent volume of distribution (Vz) for BGB-A425 and LBL-007; Cmax and Cmin for tislelizumab
3. Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): Immunogenicity: Immunogenic responses to BGB-A425, LBL-007, and tislelizumab will be assessed by summarizing the number and percentage of patients who develop detectable antidrug antibodies
4. Phase 2 (Dose Expansion): Progression-free survival (PFS), DOR, and DCR will be determined from investigator derived tumor assessments as per RECIST v1.1
5. Phase 2 (Dose Expansion): Safety and tolerability: The safety of various combinations of BGB-A425 and LBL-007 with tislelizumab will be assessed throughout the study by monitoring AEs and SAEs per NCI-CTCAE v5.0, physical examinations, electrocardiograms (ECGs), and laboratory assessments as needed
6. Phase 2 (Dose Expansion): PK: PK parameters such as Cmax, Cmin, Tmax, t1/2, and AUC0-21d for BGB-A425 and LBL-007; Cmax and Cmin for tislelizumab
7. Phase 2 (Dose Expansion): Immunogenicity: Immunogenic responses to BGB-A425, LBL-007, and tislelizumab will be assessed by summarizing the number and percentage of patients who develop detectable antidrug antibodies (ADAs).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Beigene Ltd.

Sponsor organisation

Beigene Ltd.

Address

Solaris Avenue 94

City

Camana Bay

Postcode

KY1-1108

Country

Cayman Islands

Scientific contact point

Organisation

Beigene Ltd.

Contact name

BeiGene Clinical Support

Public contact point

Organisation

Beigene Ltd.

Contact name

BeiGene Clinical Support

Third parties 10

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 135 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications