A Study to Compare Ociperlimab Plus Tislelizumab Versus Durvalumab Following Concurrent Chemoradiotherapy (cCRT) in Participants With Stage III Unresectable Non-Small Cell Lung Cancer

Phase 3TerminatedNCT04866017

BeiGene63 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non Small Cell Lung Cancer

Interventions

TislelizumabDRUG

200 mg intravenously every three weeks

DurvalumabDRUG

10 milligrams per kilogram (mg/kg) intravenously once every 2 weeks (or 1500 mg intravenously once every 4 weeks where the dosage has been approved by a local health authority)

OciperlimabDRUG

900 milligrams (mg) intravenously every three weeks

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (35)

Outcomes

Primary Outcomes

Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)

PFS is defined as the time from the date of randomization to the date of first documentation of disease progression as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or death, whichever occurred first.

Time frame: From randomization through to the end of study, planned duration was 20 months

Secondary Outcomes

Overall Survival (OS)

Defined as the time from the date of randomization until the date of death due to any cause

Time frame: From randomization through to the end of study, planned duration was 20 months

Overall Response Rate (ORR)

Defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) assessed by both the IRC and investigators per RECIST v1.1.

Time frame: From randomization through to the end of study, planned duration was 20 months

Duration of Response (DOR)

defined as the time from the first determination of a confirmed objective response assessed by both the IRC and investigators per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first

Time frame: From randomization through to the end of study, planned duration was 20 months

Time to Death or Distant Metastasis (TTDM) as Assessed by the Investigator

defined as the time from the date of randomization until the first date of distant metastasis assessed by both the IRC and investigators, or death. Distant metastasis is defined as any new lesion that is outside of the radiation field per RECIST v1.1 or proven by biopsy.

Time frame: From randomization through to the end of study, planned duration was 20 months

Data from ClinicalTrials.gov

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The chemotherapy regimen for the study treatment was selected at the investigator's discretion and may include one of the following options: * Cisplatin (50 mg/m²) on days 1 to 5 of each cycle, combined with etoposide (50 mg/m²) on days 1 and 8, both administered intravenously for 2 cycles. Each cycle was 28 days. * Carboplatin (AUC 2) weekly for 6 weeks, combined with paclitaxel (40-50 mg/m²) weekly for 6 weeks, both administered intravenously. * Cisplatin (75 mg/m²) combined with pemetrexed (500 mg/m²) on day 1 of each cycle, administered intravenously for 2 cycles. Each cycle was 21 days. * Carboplatin (AUC 5) combined with pemetrexed (500 mg/m²) on day 1 of each cycle, administered intravenously for 2 cycles. Each cycle was 21 days. The pemetrexed plus platinum regimen was only for participants with non-squamous histology.

RadiotherapyRADIATION

All participants recieved radiotherapy using either a standardized 3-dimensional conformal radiotherapy technique, or intensity modulated radiotherapy (IMRT) on a linear accelerator delivering a beam energy of ≥ 6 MV. The total dose of radiotherapy was 60 Gy, administered in 30 once-daily fractions of 2 Gy and 5 fractions per week for 6 weeks.

XCancer/Centeral Care Center

Bolivar, Missouri, United States

Southern Medical Day Care Centre

Wollongong, New South Wales, Australia

Townsville Hospital

Douglas, Queensland, Australia

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Cabrini Hospital

Malvern, Victoria, Australia

Gold Coast University Hospital

Gold Coast, Australia

Hollywood Private Hospital

Perth, Australia

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

...and 25 more locations

Progression-Free Survival 2 (PFS2)

defined as the time from randomization to the disease progression after next line of treatment, or death from any cause, whichever occurs first

Time frame: From randomization through to the end of study, planned duration was 20 months

Number of Participants Experiencing Adverse Events (AEs)

Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)

Time frame: 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)

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

Change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.

Time frame: Baseline and Cycle 6 (Each cycle is 21 days)

Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)

Change from baseline in QLQ-CL13 scores for coughing, dyspnea, and chest pain. The QLQ-LC13 is a questionnaire that measures lung cancer-specific disease and treatment symptoms. It includes questions about specific symptoms in which participants respond based on a 4-point scale, where 1 is "not at all" and 4 is "very much". Raw scores are transformed into a 0 to 100 scale via linear transformation. A lower score indicates an improvement in symptoms.

Time frame: Baseline and Cycle 6 (Each cycle is 21 days)

Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by European Quality of Life-5 Dimensions (EQ-5D-5L)

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 participant 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 participant's health state.

Time frame: Baseline and Cycle 6 (Each cycle is 21 days)

Serum Concentration of Ociperlimab

Serum concentrations of ociperlimab were measured for participants in the Ociperlimab + Tislelizumab + cCRT treatment group at predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). End of Treatment (EOT) visits occurred within 7 days after the date the investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first.

Time frame: 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)

Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group

Serum concentrations of tislelizumab were collected for participants in the Ociperlimab + Tislelizumab + cCRT treatment group at predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). End of Treatment (EOT) visits occurred within 7 days after the date investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first.

Time frame: 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)

Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group

Serum concentrations of tislelizumab were collected for participants in the Tislelizumab + cCRT treatment group at predose (within 60 minutes prior to infusion initiation) and postdose (within 30 minutes after the completion of infusion). End of Treatment (EOT) visits occurred within 7 days after the date investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first.

Time frame: 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)

Immunogenic Responses to Ociperlimab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)

Defined as the sum of treatment-boosted and treatment-induced ADA participants as a proportion percentage of the ADA-evaluable participants population and is synonymous with 'ADA Incidence'. ADA samples were collected for participants randomized to Arm A (ociperlimab and tislelizumab)

Time frame: 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

Immunogenic Responses to Tislelizumab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)

Time frame: 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)

Programmed Death-Ligand 1 (PD-L1) and T-cell Immunoreceptor With Ig and ITIM Domains (TIGIT) Expression in Archival and/or Fresh Tumor Tissues

Time frame: From randomization through to the end of study, planned duration was 20 months