Tislelizumab Plus BGB-A1217 Versus Tislelizumab Versus Durvalumab When Co-administered With Concurrent Chemoradiotherapy (cCRT) in Lung Cancer

• ClinicalTrials.gov Identifier: NCT04866017
• Recruitment Status: Recruiting
• First Posted: April 29, 2021
• Last Update Posted: October 25, 2021
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Study Description

Brief Summary:

The primary objectives of this study is to compare progression free survival (PFS) and complete response rate (CRR) between participants treated with Ociperlimab plus tislelizumab plus Concurrent Chemoradiotherapy (cCRT) followed by Ociperlimab plus tislelizumab versus participants treated with tislelizumab plus Concurrent Chemoradiotherapy (cCRT) followed by tislelizumab versus participants treated with cCRT followed by durvalumab in previously untreated, locally advanced, unresectable non-small cell lung cancer (LA NSCLC) The secondary objective of this study is to compare overall survival (OS) and PFS in programmed cell death protein ligand-1 (PD-L1) positive population between Arm A and C.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: Tislelizumab; Drug: Durvalumab; Drug: Chemotherapy; Drug: Ociperlimab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 900 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 3, Randomized, Open Label Study to Compare Ociperlimab (BGB-A1217) Plus Tislelizumab (BGB-A317) Plus Concurrent Chemoradiotherapy (cCRT) Followed by Ociperlimab Plus Tislelizumab or Tislelizumab Plus cCRT Followed by Tislelizumab Versus cCRT Followed by Durvalumab in Previously Untreated, Locally Advanced, Unresectable Non-Small Cell Lung Cancer
• Actual Study Start Date: June 17, 2021
• Estimated Primary Completion Date: January 30, 2025
• Estimated Study Completion Date: September 30, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: ociperlimab + tislelizumab + Concurrent Chemoradiotherapy (eCRT); Two cycles of ociperlimab (900 mg intravenously [IV]) combined with tislelizumab (200 mg IV) every 3 weeks (Q3W) with cCRT, followed by ociperlimab 900 mg IV combined with tislelizumab 200 mg IV Q3W up to 1 year after the cCRT phase	Drug: Tislelizumab; 100 mg/10 mL. 200 mg Q3W administered by intravenous infusion; Other Name: BGB-A317; Drug: Chemotherapy; Cisplatin, carboplatin, etoposide, paclitaxel, pemetrexed will be administered in accordance with the relevant local guidelines and/or prescribing information/summary of product characteristics; Drug: Ociperlimab; 300 mg/15 mL. 900 mg Q3W administered by intravenous infusion; Other Name: BGB-A1217
Active Comparator: Arm B: tislelizumab + Concurrent Chemoradiotherapy (cCRT); Two cycles of tislelizumab 200 mg IV Q3W combined with cCRT, followed by tislelizumab 200 mg IV Q3W up to 1 year after the cCRT phase	Drug: Tislelizumab; 100 mg/10 mL. 200 mg Q3W administered by intravenous infusion; Other Name: BGB-A317; Drug: Chemotherapy; Cisplatin, carboplatin, etoposide, paclitaxel, pemetrexed will be administered in accordance with the relevant local guidelines and/or prescribing information/summary of product characteristics
Experimental: Arm C: Concurrent Chemoradiotherapy (eCR) + durvalumab; Comparator: Arm C: Concurrent Chemoradiotherapy (cCRT) followed by durvalumab Two cycles of cCRT, followed by durvalumab 10 mg/kg IV once every 2 weeks (Q2W) (or 1500 mg Q4W where the dosage has been approved by a local health authority) up to 1 year after the cCRT phase	Drug: Durvalumab; 120 mg/2.4 mL (50 mg/mL) and 500 mg/10 mL (50 mg/mL). 10 mg/kg Q2W (or 1500 mg Q4W where the dosage has been approved by a local health authority); Drug: Chemotherapy; Cisplatin, carboplatin, etoposide, paclitaxel, pemetrexed will be administered in accordance with the relevant local guidelines and/or prescribing information/summary of product characteristics

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) in the Intent-to-treat (ITT) Analysis set as assessed by the Independent Review Committee (IRC) [ Time Frame: Up to 16 months ]
   Time from the date of randomization to the date of first documentation of disease progression assessed
2. Complete Response Rate (CRR) as assessed by the Independent Review Committee (IRC) [ Time Frame: Up to 16 months ]
   defined as the proportion of patients who achieve a complete response (CR) per Repose Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v.1.1)

Secondary Outcome Measures :

1. Overall Survival (OS) in ITT Set [ Time Frame: Up to 16 months ]
   Time from the date of randomization until the date of death due to any cause
2. Progression-Free Survival (PFS) in the PD-L1-Positive Analysis Set as assessed by the IRC [ Time Frame: Up to 16 months ]
   Time from the date of randomization to the date of first documentation of disease progression assessed
3. Overall Response Rate (ORR) in ITT Set [ Time Frame: Up to 16 months ]
   Proportion of participants who achieve a complete response (CR) or partial response (PR)
4. Duration of Response (DOR) in ITT Set [ Time Frame: Up to 16 months ]
   Time from the first determination of a confirmed objective response
5. time to death or distant metastasis (TTDM) in the Intent-to-treat (ITT) Analysis set as assessed by the investigator [ Time Frame: Up to 16 months ]
   Time from 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
6. Number of participants experiencing Adverse Events (AEs) [ Time Frame: Up to 16 months ]
7. Number of participants experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 16 months ]
8. Health Related Quality of Life (HRQoL) in the ITT set as assessed by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) [ Time Frame: Up to 16 months ]

   The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome.

   The EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). Half points are not allowed. The range is 6. First of all, raw score has to be calculated with mean values. Afterwards linear transformation is performed to be comparable. More points are considered to have a better outcome.

9. Health Related Quality of Life (HRQoL) in the ITT set as assessed by Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) [ Time Frame: Up to 16 months ]
   The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) A score of 1-4 will be administrated for each item in QLQ-LC13. The higher scores will indicate the worse outcomes.
10. Health Related Quality of Life (HRQoL) in the ITT set as assessed by European Quality of Life-5 Dimensions (EQ-5D-5L) [ Time Frame: Up to 16 months ]
    EQ-5D-5L - Is the EuroQol 5D-5L a descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
11. Serum concentration of BGB-A1217 [ Time Frame: Up to 30 minutes postdose ]
12. Serum concentration of Tislelizumab [ Time Frame: Up to 30 minutes postdose ]
13. Immunogenic responses to BGB-A1217 as assessed by the detection of anti-drug antibodies (ADAs) [ Time Frame: Up to 16 months ]
14. Immunogenic responses to Tislelizumab as assessed by the detection of anti-drug antibodies (ADAs) [ Time Frame: Up to 16 months ]
15. Evaluate PD-L1 and TIGIT expression in archival and/or fresh tumor tissues [ Time Frame: Up to 16 months ]
    before study treatment or at disease progression/reoccurrence, and their association with clinical efficacy.
16. Complete Response Rate (CRR) in the Intent-to-treat (ITT) Analysis set as assessed by the investigator [ Time Frame: Up to 16 months ]
    defined as the proportion of patients who achieve a CR

Eligibility Criteria

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

Criteria

Key Inclusion Criteria:

1. Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place).
2. Participant has newly diagnosed, histologically confirmed, locally advanced, Stage III unresectable NSCLC.
3. Measurable disease as assessed by RECIST v1.1.
4. Eastern Co-operative Oncology Group (ECOG) Performance Status of 0 or 1.
5. Patients must have adequate organ function

Key Exclusion Criteria:

1. Any prior therapy for lung cancer, including but not limited to chemotherapy, radiotherapy, targeted therapy, biologic therapy, or immunotherapy.
2. Any prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer.
3. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
4. Diagnosed with NSCLC that harbors an EGFR-sensitizing mutation or ALK gene translocation.
5. Active autoimmune diseases or history of autoimmune diseases that may relapse.
6. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study treatment.
7. Infection (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal or antiviral therapy within 14 days before the first dose of study treatment.

NOTE: Other protocol Inclusion/Exclusion criteria may apply.

Contacts and Locations

Contacts

Contact: BeiGene; +1-877-828-5568; clinicaltrials@beigene.com

Locations

United States, Missouri

XCancer/Centeral Care Center; Recruiting

Bolivar, Missouri, United States, 65613

Australia, New South Wales

Southern Medical Day Care Centre; Recruiting

Wollongong, New South Wales, Australia, NSW 2500

Australia, Queensland

Townsville Hospital; Not yet recruiting

Douglas, Queensland, Australia, 4814

Australia, South Australia

Lyell McEwin Hospital; Recruiting

Elizabeth Vale, South Australia, Australia, 5112

Australia, Tasmania

Royal Hobart Hospital; Not yet recruiting

Hobart, Tasmania, Australia

Australia, Victoria

Cabrini Hospital; Not yet recruiting

Malvern, Victoria, Australia, 3144

Australia

Gold Coast University Hospital; Not yet recruiting

Gold Coast, Australia, 4215

Hollywood Private Hospital; Not yet recruiting

Perth, Australia

Sponsors and Collaborators

BeiGene

Investigators

• Study Director: Yalan Yang, MD; BeiGene

More Information

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT04866017
• Other Study ID Numbers: BGB-A317-A1217-301; 2020-004656-14 ( EudraCT Number )
• First Posted: April 29, 2021
• Last Update Posted: October 25, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

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; Durvalumab; Antineoplastic Agents, Immunological; Antineoplastic Agents