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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)

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ClinicalTrials.gov Identifier: NCT03745222
Recruitment Status : Recruiting
First Posted : November 19, 2018
Last Update Posted : December 10, 2018
Sponsor:
Collaborator:
BeiGene
Information provided by (Responsible Party):
Celgene

Brief Summary:
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 PFS in the intent-to-treat (ITT) population. Newly diagnosed stage III subjects with histologically confirmed, locally advanced, unresectable NSCLC are eligible.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Tislelizumab Drug: Concurrent chemoradiotherapy (cCRT) Other: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 840 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE 3, RANDOMIZED, BLINDED, PLACEBO-CONTROLLED 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
Estimated Study Start Date : January 7, 2019
Estimated Primary Completion Date : August 27, 2021
Estimated Study Completion Date : October 26, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapy
Tislelizumab is given together upfront with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab monotherapy. The standard platinum-based chemotherapy options include carboplatin/ paclitaxel and cisplatin/etoposide
Drug: Tislelizumab
PD-1 inhibitor (monoclonal antibody against PD-1)
Other Name: BGB-A317

Drug: Concurrent chemoradiotherapy (cCRT)
Chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide per standard of care. Radiotherapy will also be given concurrently with chemotherapy.

Experimental: Arm 2: Placebo + cCRT followed by tislelizumab monotherapy
Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.
Drug: Tislelizumab
PD-1 inhibitor (monoclonal antibody against PD-1)
Other Name: BGB-A317

Drug: Concurrent chemoradiotherapy (cCRT)
Chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide per standard of care. Radiotherapy will also be given concurrently with chemotherapy.

Other: Placebo
Placebo

Placebo Comparator: Arm 3: Placebo + cCRT followed by placebo monotherapy
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.
Drug: Concurrent chemoradiotherapy (cCRT)
Chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide per standard of care. Radiotherapy will also be given concurrently with chemotherapy.

Other: Placebo
Placebo




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: Randomization to date of objective disease progression or death, assessed up to approximately 5 years ]
    The time from the date of randomization to the date of the first objectively documented tumor progression as assessed by blinded independent central review per RECIST v1.1 or death from any cause, whichever occurs first.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Randomization to death due to any cause, assessed up to approximately 5 years ]
    Randomization to death due to any cause

  2. Overall survival (OS) at 24 months [ Time Frame: Randomization to 24 months ]
    The proportion of subjects alive at 24 months after randomization.

  3. Objective response rate (ORR) [ Time Frame: Randomization to date of objective disease progression or death, assessed up to approximately 5 years ]
    The proportion of subjects in the ITT population who had complete response (CR) or partial response (PR) as assessed by blinded independent central review per RECIST v1.1.

  4. Duration of response (DoR) [ Time Frame: First documented objective response (RECIST 1.1) until date of objective disease progression or death, assessed up to approximately 5 years ]
    The time from the first occurrence of a documented objective response to the time of relapse, as determined by blinded independent central review per RECIST v1.1, or death from any cause, whichever comes first.

  5. Proportion of subjects alive and progression-free at 12 months (APF12) [ Time Frame: Up to approximately 12 months ]
    The proportion of subjects progression free at 12 months (APF12) will be summarized using the Kaplan-Meier estimate of PFS at 12 months.

  6. Proportion of subjects alive and progression-free at 18 months (APF18) [ Time Frame: Up to approximately 18 months ]
    The proportion of subjects alive and progression free at 18 months (APF18) will be summarized by using the Kaplan-Meier curve.

  7. Time to distant metastasis (TTDM) [ Time Frame: Randomization until first date of distant metastasis or death, assessed up to approximately 5 years ]
    Is defined as the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the radiation field according to RECIST v1.1 or proven by biopsy.

  8. Adverse Events (AEs) [ Time Frame: From enrollment until 90 days after the last dose of study treatment ]
    Safety and tolerability will be assessed from adverse events (using NCI CTCAE v5.0), laboratory tests, vital signs, ECOG performance status, physical exams, concomitant medications, and dose modifications.

  9. European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30) [ Time Frame: Up to approximately 5 years ]
    Is a 30-item, psychometrically robust, cross- culturally accepted and internationally validated questionnaire designed to be applicable to a broad spectrum of cancer subjects as a core questionnaire, assessing QoL, psychosocial burden and physical symptoms.

  10. European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire lung cancer module (EORTC QLQ-LC13) [ Time Frame: Up to approximately 5 years ]
    Subjects' disease-related symptoms will be assessed using the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13; referred to here as the LC13) which is a lung cancer specific PRO and the first module to be used in conjunction with the EORTC QLQ-C30.

  11. Proportion of subjects who continue to monotherapy phase [ Time Frame: Randomization to the first dose in the monotherapy phase (Approximately Study Day 43) ]
    Proportion of subjects who receive at least one dose of tislelizumab or placebo in the monotherapy phase before progression as determined by blinded independent central review per RECIST v1.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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. EGFR mutation and 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03745222


Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, Maryland
Center For Cancer and Blood Disorders Not yet recruiting
Bethesda, Maryland, United States, 20817
United States, Washington
Medical Oncology Associates, P.S. Recruiting
Spokane, Washington, United States, 99208
Sponsors and Collaborators
Celgene
BeiGene
Investigators
Study Director: Marie Nguyen, MD Celgene

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03745222     History of Changes
Other Study ID Numbers: BGB-A317-NSCL-001
U1111-1216-4294 ( Other Identifier: WHO )
2018-001132-22 ( EudraCT Number )
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celgene:
Locally Advanced, Unresectable Non-Small Cell Lung Cancer
Non-Small Cell Lung Cancer
NSCLC
Randomized
BGB-A317
Tislelizumab
PD-1

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Etoposide
Cisplatin
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors