A Study of Tislelizumab (BGB-A317) Plus Chemoradiotherapy Followed by Tislelizumab Monotherapy in Newly Diagnosed, Stage III Subjects With Locally Advanced, Unresectable Non-small Cell Lung Cancer (RATIONALE001)

Celgene

Status and phase: Terminated; Phase 3

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Concurrent chemoradiotherapy (cCRT); Other: Placebo; Drug: Tislelizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03745222

BGB-A317-NSCL-001

2018-001132-22 (EudraCT Number)

U1111-1216-4294 (Other Identifier)

Details and patient eligibility

About

This is a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed to compare the efficacy and safety of tislelizumab in combination with concurrent chemoradiotherapy (cCRT) followed by tislelizumab monotherapy versus cCRT alone, and tislelizumab given sequentially after cCRT versus cCRT alone, in newly diagnosed stage III subjects with locally advanced, unresectable non-small cell lung cancer (NSCLC). The primary endpoint is centrally-assessed progression free survival (PFS) in the intent-to-treat (ITT) population. .

Enrollment: 1 patient

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Newly diagnosed, histologically confirmed, locally advanced, stage III unresectable non small cell lung cancer (NSCLC).

   Staging will be confirmed at screening by positron emission tomography-computed tomography (PET/CT) and brain imaging by magnetic resonance imaging (MRI) or computed tomography (CT) with contrast.

2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

3. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene translocation status available prior to randomization.

4. Provision of fresh or archival tumor tissue or discussion with Sponsor.

5. Adequate hematologic and end-organ function.

Exclusion criteria

1. Prior therapies including those targeting PD-1 or PD-L1 or chemotherapy, radiation, targeted therapy, biologic therapy, immunotherapy or investigational agent used to control non-small cell lung cancer (NSCLC).
2. History of severe hypersensitivity reactions to other monoclonal antibodies or any contraindication to the planned chemotherapy regimen.
3. History of, or ongoing, interstitial lung disease; pneumonitis requiring steroids; or clinically significant pericardial effusion.
4. Any active malignancy less than or equal to 2 years before randomization, with the exception of non-small cell lung cancer (NSCLC) and any locally recurring cancer that has been treated curatively.
5. Severe chronic or active infections including those requiring systemic antibacterial, antifungal or antiviral therapy; known human immunodeficiency virus (HIV) infection; untreated chronic hepatitis B or chronic hepatitis B virus carries or active hepatitis C; or active autoimmune disease.
6. Prior allogeneic stem cell transplantation or organ transplantation.
7. Significant cardiovascular disease or other condition which places the patient at risk.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1 participants in 3 patient groups, including a placebo group

Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapy

Experimental group

Description:

Tislelizumab 200 mg is administered by intravenous (IV) administration and given together upfront with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV adminstration monotherapy. The standard platinum-based chemotherapy options include carboplatin/ paclitaxel and cisplatin/etoposide

Treatment:

Drug: Tislelizumab

Drug: Concurrent chemoradiotherapy (cCRT)

Arm 2: Placebo + cCRT followed by tislelizumab monotherapy

Experimental group

Description:

Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV administration monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.

Treatment:

Drug: Tislelizumab

Drug: Concurrent chemoradiotherapy (cCRT)

Other: Placebo

Arm 3: Placebo + cCRT followed by placebo monotherapy

Placebo Comparator group

Description:

Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by placebo monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.

Treatment:

Drug: Concurrent chemoradiotherapy (cCRT)

Other: Placebo