Clinical trial NCT04866017: A Study to Compare Ociperlimab Plus Tislelizumab Versus Durvalumab Following Concurrent Chemoradiotherapy (cCRT) in Participants With Stage III Unresectable Non-Small Cell Lung Cancer
Official title: A Phase 3, Randomized, Open-Label Study to Compare Ociperlimab (BGB-A1217) Plus Tislelizumab (BGB-A317) Versus Durvalumab in Patients With Locally Advanced, Unresectable, PD-L1-Selected Non-Small Cell Lung Cancer Whose Disease Has Not Progressed After Concurrent Chemoradiotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2021-04-29
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the safety and efficacy of ociperlimab in combination with tislelizumab compared to durvalumab in adults with stage III unresectable PD-L1-selected non-small cell lung cancer whose disease has not progressed after cCRT.

Detailed description: The study initiated with Protocol Amendment 1.0 (PA 1; dated on 16 April 2021). In April 2022 Protocol Amendment 2 (PA 2) was implemented. In PA 1, participants with newly diagnosed, histologically confirmed, unresectable locally advanced NSCLC and evaluable PD-L1 expression all comers were enrolled; cCRT was given within the study. In PA 2, the enrollment of the target population was revised into participants with unresectable locally advanced NSCLC whose disease has not progressed after definitive, platinum-based cCRT and with PD-L1 expression on ≥ 1% of tumor cells as assessed by the central lab; cCRT was given outside of the study.

After implementation of PA 2, participants who were randomized under PA 1 were given the option to continue assigned study treatment or to discontinue assigned treatment and begin standard of care treatment outside of the study. Participants enrolled under PA 1 were excluded from the primary and secondary analysis specified by PA 2.

This study was subsequently terminated by the Sponsor prior to enrollment of any participants under PA 2.

Eligibility criteria: Key Inclusion Criteria:

1. Age ≥ 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place).
2. Participant has histologically or cytologically confirmed, locally advanced, unresectable Stage III NSCLC (AJCC Cancer Staging Manual 2017, derived from IASLC) prior to initiation of cCRT.
3. Participant must have completed at least 2 cycles of platinum-based chemotherapy concurrent with radiotherapy
4. Participants must have not experienced PD following definitive, platinum-based cCRT.
5. Eastern Co-operative Oncology Group (ECOG) Performance Status of 0 or 1.
6. Participants must have adequate organ function
7. Agree to provide archival tissue (formalin-fixed paraffin-embedded block containing tumor \[preferred\] or approximately 6 to 15 freshly cut unstained slides) or fresh biopsy obtained prior to cCRT (if archival tissue is not available) for prospective central evaluation of PD-L1 levels and retrospective analysis of other biomarkers.

Key Exclusion Criteria:

1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT, or any other antibody or drugs specifically targeting T-cell co-stimulation or checkpoint pathways.
2. Diagnosed with NSCLC that harbors an epidermal growth factor receptor (EGFR) sensitizing mutation, anaplastic lymphoma kinase (ALK) gene translocation, ROS1 gene translocation or RET gene rearrangement.
3. Participants who received systemic anticancer treatment besides the specified cCRT.
4. Any unresolved toxicity CTCAE \> Grade 2 from the prior cCRT.
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 \[in Japan, prednisolone\] 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: Antiviral therapy is permitted for participants with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

NOTE: Other protocol Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
timeFrame: From randomization through to the end of study, planned duration was 20 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization through to the end of study, planned duration was 20 months
measure: Overall Response Rate (ORR)
timeFrame: From randomization through to the end of study, planned duration was 20 months
measure: Duration of Response (DOR)
timeFrame: From randomization through to the end of study, planned duration was 20 months
measure: Time to Death or Distant Metastasis (TTDM) as Assessed by the Investigator
timeFrame: From randomization through to the end of study, planned duration was 20 months
measure: Progression-Free Survival 2 (PFS2)
timeFrame: From randomization through to the end of study, planned duration was 20 months
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From first dose to 30 days after the last dose or initiation of a new anticancer therapy, whichever occured first; through study completion data cut-off date of October 17th, 2023 (maximum time on treatment was 16 months)
measure: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status
timeFrame: Baseline and Cycle 6 (Each cycle is 21 days)
measure: Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)
timeFrame: Baseline and Cycle 6 (Each cycle is 21 days)
measure: Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by European Quality of Life-5 Dimensions (EQ-5D-5L)
timeFrame: Baseline and Cycle 6 (Each cycle is 21 days)
measure: Serum Concentration of Ociperlimab
timeFrame: Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1, 5 and EOT visit (Each Cycle was 21 days)
measure: Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group
timeFrame: Predose at Day 1 of Cycles 1, 2, 5, 9, 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (each cycle was 21 days)
measure: Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group
timeFrame: Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (Each Cycle is 21 days)
measure: Immunogenic Responses to Ociperlimab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)
timeFrame: Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days). Maximum number of treatment cycles was 19
measure: Immunogenic Responses to Tislelizumab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)
timeFrame: Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days, maximum number of treatment cycles was 19)
measure: Programmed Death-Ligand 1 (PD-L1) and T-cell Immunoreceptor With Ig and ITIM Domains (TIGIT) Expression in Archival and/or Fresh Tumor Tissues
timeFrame: From randomization through to the end of study, planned duration was 20 months
Other outcomes:
Locations:
city: Bolivar
country: United States
facility: XCancer/Centeral Care Center
state: Missouri
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: Douglas
country: Australia
facility: Townsville Hospital
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Malvern
country: Australia
facility: Cabrini Hospital
state: Victoria
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital
city: Perth
country: Australia
facility: Hollywood Private Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Changsha
country: China
facility: Hunan Cancer Hospital - GCP Office
state: Hunan
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University Branch Shizi
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jinan
country: China
facility: Shandong Cancer Hospital and Institute, Shandong First Medical University
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
state: Zhejiang
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changzhou
country: China
facility: Changzhou Cancer Hospital
city: Jieyang
country: China
facility: Jieyang People'S Hospital (Jieyang Affiliated Hospital, Sun Yat-Sen University )
city: Alcorcon
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
state: Madrid
city: Barcelona
country: Spain
facility: Instituto Oncologico Dr. Rosell
city: Girona
country: Spain
facility: Ico Girona
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
References: