Mass General - Division of Clinical Research

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

Purpose

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%).

Conditions

Non-small Cell Lung Cancer
Metastatic Non-small Cell Lung Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

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.

Exclusion Criteria

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.

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Sub-study 1: Arm 1A	Tislelizumab + BGB-A445	Drug: Tislelizumab Administered by intravenous infusion Drug: BGB-A445 Administered by intravenous infusion
Experimental Sub-study 1: Arm 2A	Tislelizumab + LBL-007	Drug: Tislelizumab Administered by intravenous infusion Drug: LBL-007 Administered by intravenous infusion
Experimental Sub-study 1: Arm 3A	Tislelizumab + BGB-15025	Drug: Tislelizumab Administered by intravenous infusion Drug: BGB-15025 Administered Orally
Active Comparator Sub-study 1: Reference Arm Tislelizumab alone	Tislelizumab alone	Drug: Tislelizumab Administered by intravenous infusion
Experimental Sub-study 2: Arm 1B	Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445	Drug: Tislelizumab Administered by intravenous infusion Drug: BGB-A445 Administered by intravenous infusion Drug: Carboplatin Investigator's choice; administered by intravenous infusion Drug: Cisplatin Investigator's choice; administered by intravenous infusion Drug: pemetrexed Investigator's choice; administered by intravenous infusion Drug: Paclitaxel Investigator's choice; administered by intravenous infusion Drug: Nab paclitaxel Investigator's choice; administered by intravenous infusion
Experimental Sub-study 2: Arm 2B	Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007	Drug: Tislelizumab Administered by intravenous infusion Drug: LBL-007 Administered by intravenous infusion Drug: Carboplatin Investigator's choice; administered by intravenous infusion Drug: Cisplatin Investigator's choice; administered by intravenous infusion Drug: pemetrexed Investigator's choice; administered by intravenous infusion Drug: Paclitaxel Investigator's choice; administered by intravenous infusion Drug: Nab paclitaxel Investigator's choice; administered by intravenous infusion
Experimental Sub-study 2: Arm 3B	Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025	Drug: Tislelizumab Administered by intravenous infusion Drug: Carboplatin Investigator's choice; administered by intravenous infusion Drug: Cisplatin Investigator's choice; administered by intravenous infusion Drug: pemetrexed Investigator's choice; administered by intravenous infusion Drug: Paclitaxel Investigator's choice; administered by intravenous infusion Drug: Nab paclitaxel Investigator's choice; administered by intravenous infusion Drug: BGB-15025 Administered Orally
Active Comparator Sub-study 2: Reference Arm	Tislelizumab + investigator's choice of histology-appropriate chemotherapy	Drug: Tislelizumab Administered by intravenous infusion Drug: Carboplatin Investigator's choice; administered by intravenous infusion Drug: Cisplatin Investigator's choice; administered by intravenous infusion Drug: pemetrexed Investigator's choice; administered by intravenous infusion Drug: Paclitaxel Investigator's choice; administered by intravenous infusion Drug: Nab paclitaxel Investigator's choice; administered by intravenous infusion

More Details

Status: Active, not recruiting
Sponsor: BeiGene