Comparison of Efficacy and Safety of Tislelizumab (BGB-A317) Versus Docetaxel as Treatment in the Second- or Third-line Setting in Participants With Non-Small Cell Lung Cancer (NSCLC) (RATIONALE-303)

BeiGene

Status and phase: Completed; Phase 3

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Tislelizumab; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT03358875

2018-000245-39 (EudraCT Number)

CTR20171112 (Registry Identifier)

BGB-A317-303

Details and patient eligibility

About

The purpose of this study is to show that tislelizumab will improve overall survival in participants with Stage IIIB or IV non-small cell lung cancer when compared to docetaxel in second or third-line treatment setting.

Full description

This is a randomized, open-label, multicenter Phase 3 study in adult participants with histologically confirmed, locally advanced or metastatic (Stage IIIB or IV), NSCLC (squamous or non-squamous) who have disease progression during or after a platinum-containing regimen.

Enrollment: 805 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Age ≥ 18 years.
2. Signed Informed Consent Form.
3. Histologically confirmed locally advanced or metastatic (Stage IIIB or IV) NSCLC of either squamous or non-squamous histology types with disease progression during or following treatment with at least one platinum-containing regimen, but no more than 2 lines of systemic therapy.
4. Participants must be able to provide fresh or archival tumor tissues for central assessment of PD-L1 expression in tumor cells. Participants with non-squamous histology must provide evidence of not harboring sensitizing epidermal growth factor (EGFR) mutation tested by a histology-based method.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
6. Adequate hematologic and end-organ function.
7. Expected life span > 12 weeks.
8. Willing to be compliance with birth control requirement during pre-specified study participating period

Key Exclusion Criteria:

1. Prior therapies of docetaxel or treatment targeting programmed cell death protein 1 (PD-1), PD-L1 or cytotoxic T-lymphocyte associated protein 4 (CTLA-4).
2. Harboring EGFR sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation.
3. Unresolved side effects of Grade 2 and above from prior anti-cancer therapies, except for adverse events (AEs) not constituting a likely safety risk (e.g. alopecia, rash, pigmentation, specific lab abnormalities).
4. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
5. History of interstitial lung disease, non-infectious pneumonitis or participants with significantly impaired pulmonary function, or who require supplemental oxygen at baseline.
6. With uncontrollable pleural effusion, pericardial effusion, or clinically significant ascites requiring interventional treatment.
7. Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
8. Severe chronic or active infection requiring systemic treatment.
9. Known human immunodeficiency virus (HIV) infection, participants with untreated chronic hepatitis B, active vaccination treatment.
10. Insufficient cardiac functions and other underlying unfavorable cardiovascular conditions.
11. Prior allogeneic stem cell transplantation or organ transplantation.
12. Active autoimmune diseases or history of autoimmune diseases that may relapse.
13. With conditions requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications.
14. With severe underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse that may affect the explanation of drug toxicity or AEs or result in impaired compliance with study conduct.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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805 participants in 2 patient groups

Tislelizumab

Experimental group

Description:

Participants received tislelizumab 200 mg intravenously (IV) once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first.

Treatment:

Drug: Tislelizumab

Docetaxel

Active Comparator group

Description:

Participants received docetaxel 75 mg/m² IV once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first.

Treatment:

Drug: Docetaxel