Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations in Participants With Resectable Non-Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
This is a randomized, open-label, multicenter, Phase 2, umbrella study to evaluate the preliminary efficacy, safety, and pharmacodynamics of tislelizumab as monotherapy and in combination with investigational agents as neoadjuvant treatment in Chinese participants with resectable Stage II to IIIA non-small cell lung cancer (NSCLC). The study is designed with the flexibility of adding treatment arms as new treatments become available or discontinuing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and of modifying the participant population.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A: Tislelizumab Monotherapy Tislelizumab on a 3-week cycle for 2 cycles, followed by surgical resection (each cycle is 21 days) |
Drug: Tislelizumab
Administered as an intravenous infusion
Other Names:
|
| Experimental: Arm B: Tislelizumab and Ociperlimab Tislelizumab + ociperlimab on a 3-week cycle for 2 cycles, followed by surgical resection (each cycle is 21 days) |
Drug: Tislelizumab
Administered as an intravenous infusion
Other Names:
Drug: Ociperlimab
Administered as an intravenous infusion
Other Names:
|
| Experimental: Arm C: Tislelizumab and LBL-007 Tislelizumab + LBL-007 on a 3-week cycle for 2 cycles, followed by surgical resection (each cycle is 21 days) |
Drug: Tislelizumab
Administered as an intravenous infusion
Other Names:
Drug: LBL-007
Administered as an intravenous infusion
|
Outcome Measures
Primary Outcome Measures
- Major Pathological Response (MPR) [Up to approximately 12 weeks after first dose]
MPR is defined as the proportion of participants with ≤ 10% residual viable tumor in the resected primary tumor and all resected lymph nodes as assessed by blinded independent pathology review (BIPR)
Secondary Outcome Measures
- Pathological complete response (pCR) [Up to approximately 12 weeks after first dose]
pCR is defined as the proportion of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes as assessed by the BIPR
- Event-free survival (EFS) [Up to approximately 4 years]
EFS is defined as the time from randomization until any of the following events, whichever occurs first: radiographic disease progression that precludes definitive surgery, local or distant recurrence, as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause
- Overall survival (OS) [Up to approximately 4 years]
OS is defined as the time from the date of randomization to the date of death due to any cause
- Disease-free survival (DFS) [Up to approximately 4 years]
DFS is defined as the time from the first date of no disease (ie, participants who underwent margin-negative [R0] resection) to local or distant recurrence, as assessed by the investigator according to RECIST v1.1, or death due to any cause, whichever occurs first
- Number of participants with adverse events [Up to approximately 4 years]
Number of participants with treatment-emergent adverse events, including serious adverse events and immune-mediated adverse events (imAEs), with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0
- Proportion of participants who undergo surgical resection [Up to approximately 12 weeks after first dose]
Proportion of participants who undergo surgical resection within a scheduled period after receiving any dose of investigational agents, delayed or canceled surgery, duration of surgery and surgical approach
- Serum or plasma concentrations of investigational agents [Up to 30 days after last dose]
- Number of participants with anti-drug antibodies (ADAs) [Up to 30 days after last dose]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
-
Histologically confirmed Stage II-IIIA NSCLC (per the Eighth American Joint Committee on Cancer/Union Internationale Contre le Cancer [NSCLC] staging system)
-
Participant must have tumor PD-L1 expression ≥ 1% determined by a local laboratory with an approved assay
-
Tumor PD-L1 expression ≥ 50% for participants enrolled for Arm A, Arm B, and Arm C in Stage 1
-
Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent
-
Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained ≤ 7 days before randomization
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Provide formalin-fixed paraffin-embedded block (preferred) or at least 18 freshly cut unstained FFPE slides of the primary tumor for biomarker evaluation during screening
Exclusion Criteria:
-
Any prior antineoplastic therapy(ies) for current lung cancer (eg, radiotherapy, targeted therapies, ablation, or other systemic or local antineoplastic treatment)
-
Participants with large cell neuroendocrine carcinoma (LCNEC)
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The presence of locally advanced unresectable NSCLC regardless of stage or metastatic disease (Stage IV). Mediastinal lymph node samples are required for clinical staging to assess nodal involvement in participants with contralateral mediastinal adenopathy on CT scan
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History of interstitial lung disease, pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases
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Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection
-
Known actionable mutations (including but not limited to EGFR, ALK, BRAF, RET, and ROS1 mutations)
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- BeiGene
Investigators
- Study Director: Study Director, BeiGene
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGB-LC-202