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

Sponsor

BeiGene (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05635708

Collaborator

(none)

300

Enrollment

Arms

32.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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%).

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer Metastatic Non-small Cell Lung Cancer	Drug: Tislelizumab Drug: BGB-A445 Drug: LBL-007 Drug: Carboplatin Drug: Cisplatin Drug: pemetrexed Drug: Paclitaxel Drug: Nab paclitaxel	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Master Protocol: A Phase 2, Open-label, Multi-arm Study of Tislelizumab in Combination With Investigational Agents With or Without Chemotherapy in Patients With Previously Untreated, Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Nov 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sub-study 1: Experimental Arm 1A Tislelizumab + BGB-A445	Drug: Tislelizumab Administered by intravenous infusion Drug: BGB-A445 Administered by intravenous infusion
Experimental: Sub-study 1: Experimental Arm 2A Tislelizumab + LBL-007	Drug: Tislelizumab Administered by intravenous infusion Drug: LBL-007 Administered by intravenous infusion
Experimental: Sub-study 1: Reference Arm Tislelizumab alone	Drug: Tislelizumab Administered by intravenous infusion
Experimental: Sub-study 2 : Experimental Arm 1A Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445	Drug: Tislelizumab Administered by intravenous infusion Drug: BGB-A445 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: Experimental Arm 1B 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
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

Outcome Measures

Primary Outcome Measures

Confirmed overall response rate (ORR) [Up to 3 Years]
ORR is defined as the percentage of participants with partial or complete response, as assessed by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1

Secondary Outcome Measures

Progression-free survival (PFS) [Up to 3 Years]
PFS is defined as the time from date of randomization, or the first dose for safety lead-in participants , until first documentation of progression or death, whichever comes first, as assessed by the investigator using RECIST v1.
Duration of Response (DOR) [Up to 3 Years]
DOR is defined as the time from the first determination of a confirmed response per RECIST v1.1 until the first documentation of progression or death, whichever comes first as assessed by the investigator
Clinical Benefit Rate (CBR) [Up to 3 Years]
CBR is defined as the percentage of participants with a best overall response of a complete response, partial response, or durable stable disease, as assessed by the investigator using RECIST v1.1
Disease Control Rate (DCR) [Up to 3 Years]
DCR is defined as the percentage of participants with a best overall response of complete response, partial response, or stable disease, as assessed by the investigator using RECIST v1.1
Number of participants with adverse events (AEs) [Up to 3 Years]
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results.
Plasma or serum concentrations of tislelizumab [Up to 30 days after last dose]
Plasma or serum concentrations of BGB-A445 [Up to 30 days after last dose]
Plasma or serum concentrations of LBL-007 [Up to 30 days after last dose]
Number of participants with anti-drug antibodies (ADAs) to tislelizumab [Up to 30 days after last dose]
Number of participants with anti-drug antibodies (ADAs) to LBL-007 [Up to 30 days after last dose]
Number of participants with anti-drug antibodies (ADAs) to BGB-A445 [Up to 30 days after last dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed NSCLC (nonsquamous or squamous) that is locally advanced or recurrent and not eligible for curative surgery and/or definitive chemoradiotherapy, or metastatic NSCLC.
No prior systemic treatment given as primary therapy for metastatic NSCLC. Prior adjuvant/neoadjuvant chemotherapy or definitive chemoradiation/adjuvant radiotherapy for locally advanced disease is allowed provided the last dose of chemotherapy and/or radiotherapy occurred at least 6 months before randomization/enrollment.
Evaluable tumor PD-L1 expression as determined by a local laboratory or by central laboratory on archival tumor tissue or fresh biopsy. Patients with unknown PD-L1 expression will not be eligible for this study.
At least 1 measurable lesion as defined per RECIST v1.1.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Exclusion Criteria:

Has mixed small cell lung cancer.
Participants with known actionable mutations for which a targeted therapy has been approved by the local health authority will be excluded.
Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, anti-LAG-3 or any other antibody or drug targeting T-cell costimulation or immune checkpoint pathways. Note: Patients who received prior neoadjuvant, adjuvant or immuno-oncology therapies targeting PD-1 or PD-L1 in consolidation are eligible, if there has been a treatment-free interval of ≥ 6 months from last dose of immuno-oncology therapy prior to radiologic recurrence of disease.
Has received any Chinese herbal medicine or Chinese patent medicines used to control cancer ≤ 14 days before randomization/enrollment.
Active leptomeningeal disease or uncontrolled, untreated brain metastasis, or active autoimmune diseases.

NOTE: Other protocol and sub-study protocol defined criteria may apply