A Study of Tislelizumab in Combination With Investigational Agents in Participants With Non-Small Cell Lung Cancer

BeiGene

Status and phase: Active, not recruiting; Phase 2

Conditions: Metastatic Non-small Cell Lung Cancer; Non-small Cell Lung Cancer

Treatments: Drug: pemetrexed; Drug: Tislelizumab; Drug: BGB-15025; Drug: Carboplatin; Drug: Nab paclitaxel; Drug: BGB-A445; Drug: Cisplatin; Drug: LBL-007; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT05635708

CTR20230892 (Other Identifier)

2022-502738-18-00 (EU Trial (CTIS) Number)

BGB-LC-201

Details and patient eligibility

About

The purpose of this study is to assess the antitumor activity, safety, and tolerability of tislelizumab plus investigational agent(s) with or without chemotherapy. This study is structured as a master protocol with separate sub- studies. Sub-study 1 includes participants with non-small cell lung cancer (NSCLC) with high programmed cell death protein ligand-1 (PD-L1) expression (≥ 50%), and Sub-study 2 includes participants with NSCLC with low or negative (PD-L1) expression (< 50%).

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including nonsquamous or squamous subtypes, that is either locally advanced or recurrent and not eligible for curative surgery and/or definitive chemoradiotherapy, or metastatic NSCLC.
2. No prior systemic therapy administered as the primary treatment for metastatic NSCLC. Prior adjuvant or neoadjuvant chemotherapy, definitive chemoradiation, or adjuvant radiotherapy for locally advanced disease is permitted, provided the last dose of chemotherapy and/or radiotherapy occurred at least 6 months prior to randomization/enrollment.
3. Tumor programmed death-ligand 1 (PD-L1) expression must be evaluable, as determined by a local or central laboratory using archival tumor tissue or a fresh biopsy. Participants with unknown PD-L1 expression are not eligible.
4. At least one measurable lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Key Exclusion Criteria:

1. Diagnosis of mixed small cell lung cancer.

2. Known genomic alterations for which effective targeted therapies are available according to local standard of care, including but not limited to:

   • Epidermal growth factor receptor (EGFR) mutations
   • Anaplastic lymphoma kinase (ALK) rearrangements
   • B-Raf proto-oncogene (BRAF) mutations
   • Rearranged during transfection (RET) fusions
   • c-ros oncogene 1 (ROS1) rearrangements

3. Participants with nonsquamous NSCLC and unknown EGFR mutation status must undergo local testing. Those found to have EGFR-sensitizing mutations will be excluded.

4. Prior treatment with immune-based therapies that target immune checkpoint pathways, including:

   • PD-1 (programmed cell death protein 1) inhibitors
   • PD-L1 (programmed death-ligand 1) inhibitors
   • PD-L2 (programmed death-ligand 2) inhibitors
   • TIGIT (T cell immunoreceptor with Ig and ITIM domains) inhibitors
   • LAG-3 (lymphocyte activation gene 3) inhibitors

5. Participants previously treated with these agents in a neoadjuvant, adjuvant, or consolidation setting may be eligible if a treatment-free interval of at least 6 months has elapsed since the last dose and radiologic evidence of recurrence is present.

6. Use of Chinese herbal medicines or Chinese patent medicines intended for cancer control within 14 days prior to randomization/enrollment.

7. Presence of active leptomeningeal disease, untreated or uncontrolled brain metastases, or active autoimmune disease.

Note: Additional protocol-defined and sub-study-specific criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 8 patient groups

Sub-study 1: Arm 1A

Experimental group

Description:

Tislelizumab + BGB-A445

Treatment:

Drug: BGB-A445

Drug: Tislelizumab

Sub-study 1: Arm 2A

Experimental group

Description:

Tislelizumab + LBL-007

Treatment:

Drug: LBL-007

Drug: Tislelizumab

Sub-study 1: Arm 3A

Experimental group

Description:

Tislelizumab + BGB-15025

Treatment:

Drug: BGB-15025

Drug: Tislelizumab

Sub-study 1: Reference Arm Tislelizumab alone

Active Comparator group

Description:

Tislelizumab alone

Treatment:

Drug: Tislelizumab

Sub-study 2: Arm 1B

Experimental group

Description:

Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445

Treatment:

Drug: Paclitaxel

Drug: Cisplatin

Drug: BGB-A445

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: pemetrexed

Drug: Tislelizumab

Sub-study 2: Arm 2B

Experimental group

Description:

Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007

Treatment:

Drug: Paclitaxel

Drug: Cisplatin

Drug: LBL-007

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: pemetrexed

Drug: Tislelizumab

Sub-study 2: Arm 3B

Experimental group

Description:

Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025

Treatment:

Drug: Paclitaxel

Drug: Cisplatin

Drug: Nab paclitaxel

Drug: BGB-15025

Drug: Carboplatin

Drug: pemetrexed

Drug: Tislelizumab

Sub-study 2: Reference Arm

Active Comparator group

Description:

Tislelizumab + investigator's choice of histology-appropriate chemotherapy

Treatment:

Drug: Paclitaxel

Drug: Cisplatin

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: pemetrexed

Drug: Tislelizumab