This study has been transitioned to CTIS with ID 2023-507317-10-00 check the CTIS register for the current data. Primary:• To compare progression free survival (PFS) between Arm A (ociperlimab in combination with tislelizumab) and Arm B (…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Locally Advanced, Unresectable, or Metastatic Non Small Cell Lung Cancer
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary:
• PFS as assessed by investigators (time from the date of randomization to the
date of the first objectively documented tumor progression per RECIST v1.1, or
death, whichever occurs first) in the ITT Analysis Set of Arm A (ociperlimab in
combination with tislelizumab) and Arm B (pembrolizumab followed by placebo)
• OS (time from the date of randomization to the date of death due to any
cause) in the ITT Analysis Set of Arm A (ociperlimab in combination with
tislelizumab) and Arm B (pembrolizumab followed by placebo)
Secondary outcome
Secondary:
• PFS as assessed by the BIRC in Arm A (ociperlimab in combination with
tislelizumab) and Arm B (pembrolizumab followed by placebo)
• ORR as assessed by investigators (proportion of patients with a documented,
confirmed complete response [CR] or partial response [PR] per RECIST v1.1) and
DOR as assessed by investigators (time from the first determination of an
objective response per RECIST v1.1 until the first documentation of progression
or death, whichever occurs first) in Arm A (ociperlimab in combination with
tislelizumab) and Arm B (pembrolizumab followed by placebo)
• HRQoL as assessed via patient reported outcomes (PRO) using the European
Organization for Research and Treatment of Cancer Quality of Life Questionnaire
Core 30 (EORTC QLQ-C30), its lung cancer module Quality of Life Questionnaire
Lung Cancer 13 (QLQ-LC13), and the 5 Level EuroQol 5 Dimension (EQ-5D-5L)
questionnaire in Arm A (ociperlimab in combination with tislelizumab) and Arm B
(pembrolizumab followed by placebo). PRO endpoints include the EORTC QLQ-C30's
global health status/QoL (GHS), physical function and fatigue scales, and the
QLQ-LC13's index score, dyspnea, coughing, hemoptysis and pain in chest, pain
in arms/shoulders and peripheral neuropathy scales.
• TTD, defined as time from randomization to the first occurence of worsening
scores (10-point change, to be defined in the Statistical Analysis Plan [SAP]
if otherwise) for 2 consecutive assessments or 1 assessment followed by death
from any cause before the next scheduled data collection
• The incidence and severity of adverse events (AEs) according to National
Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0
(NCI-CTCAE v5.0) in Arm A (ociperlimab in combination with tislelizumab)
Background summary
Ociperlimab and tislelizumab are experimental drugs. This means they have not
been approved for non-small cell lung cancer by the regulatory agencies in your
country. As of 20 July 2022, tislelizumab has been given to approximately 2173
participants taking part in other research studies as a single drug. As of 28
July 2022, ociperlimab has been given to approximately 277 participants
involving ociperlimab as a single drug (9 patients) or in combination with
tislelizumab (268 patients).
Ociperlimab and tislelizumab are both antibodies. An antibody is a common type
of protein found in your body, through which the immune system finds and
destroys bacteria, viruses, and other foreign substances that enter your body.
Antibodies can also be produced in the laboratory and used for treating
subjects. Currently, several antibodies have been approved for the treatment of
cancer and other diseases.
Tislelizumab and pembrolizumab bind to PD-1, which is a protein present on the
surface of immune cells. The PD-1 protein becomes active when its partner
(PD-L1) binds to it like a handshake and prevents your body*s immune cells from
killing tumor cells. The result of this binding is like stepping on a car
brake, but this brake stops your immune cells. Tislelizumab can block PD-1 and
its partner PD-L1 from binding to each other, thereby releasing the *brake* and
restoring the tumor-killing function of immune cells.
Your body*s immune cells have another protein present on their surface, which
is referred to as TIGIT (or T-cell immunoglobulin and immunoreceptor
tyrosine-based inhibitory motif domain). The TIGIT protein functions similarly
to PD-1 and works together with PD-1 to stop your body*s immune cells from
killing tumor cells. Like PD-1, TIGIT becomes active when it binds to one of
its ligands (partners). The ociperlimab antibody blocks the interaction between
TIGIT and its ligands to further release the *brake* on your immune cells,
which may increase the tumor killing capacity of your immune cells.
Study objective
This study has been transitioned to CTIS with ID 2023-507317-10-00 check the CTIS register for the current data.
Primary:
• To compare progression free survival (PFS) between Arm A (ociperlimab in
combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) in
the Intent to Treat (ITT) Analysis Set as assessed by investigators according
to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
• To compare overall survival (OS) between Arm A (ociperlimab in combination
with tislelizumab) and Arm B (pembrolizumab followed by placebo) in the ITT
Analysis Set
Secondary:
• To compare PFS between Arm A (ociperlimab in combination with tislelizumab)
and Arm B (pembrolizumab followed by placebo) in the ITT Analysis Set as
assessed by the Blinded Independent Review Committee (BIRC) according to RECIST
v1.1
• To compare the overall response rate (ORR) and duration of response (DOR)
between Arm A (ociperlimab in combination with tislelizumab) and Arm B
(pembrolizumab followed by placebo) in the ITT Analysis Set as assessed by
investigators according to RECIST v1.1
• To compare health-related quality of life (HRQoL) and time to deterioration
(TTD) between Arm A (ociperlimab in combination with tislelizumab) and Arm B
(pembrolizumab followed by placebo) in the ITT Analysis Set
• To further investigate the safety and tolerability of ociperlimab in
combination with tislelizumab
Exploratory:
• To compare the disease control rate (DCR), clinical benefit rate (CBR), and
time to response (TTR) between Arm A (ociperlimab in combination with
tislelizumab) and Arm B (pembrolizumab followed by placebo) in the ITT Analysis
Set as assessed by investigators according to RECIST v1.1
• To compare ORR, DOR, DCR, CBR, and TTR between Arm A (ociperlimab in
combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) in
the ITT Analysis Set as assessed by the BIRC according to RECIST v1.1
• To evaluate OS, as well as ORR, DOR, PFS, DCR, CBR, and TTR as assessed by
the BIRC and investigators according to RECIST v1.1, in the ITT Analysis Set of
Arm C (tislelizumab followed by placebo)
• To evaluate PFS after next line of treatment (PFS2)
• To characterize the pharmacokinetics (PK) of ociperlimab and tislelizumab
• To evaluate the potential association of exploratory biomarkers with response
or resistance to treatment with ociperlimab and tislelizumab and with patient
prognosis.
• To determine host immunogenicity to ociperlimab and tislelizumab
• To further investigate the safety and tolerability of tislelizumab
• Patient-reported changes in non-small cell lung cancer (NSCLC) symptom
severity from baseline via the PGI-S questionnaire and patient reported
treatment-related side effect burden via the PRTSE questionnaire in Arms A, B,
and C
• To measure HRQoL in Arm C in the ITT Analysis Set
Study design
This is a randomized, double-blind, multicenter, Phase 3 study designed to
evaluate the efficacy and safety of ociperlimab + tislelizumab compared with
that of pembrolizumab in patients with PD-L1-selected non-small cell lung
cancer (NSCLC) who have locally advanced or recurrent disease
that is unresectable or not amenable to radiotherapy, with or without
chemoradiotherapy, or previously untreated metastatic disease, and whose
tumors do not harbor epidermal growth factor receptor (EGFR)-sensitizing
mutations, anaplastic lymphoma kinase (ALK) translocations, BRAF V600E
mutations, or ROS1 mutations. The efficacy and safety of tislelizumab alone
will be explored in a cohort of the same patient population.
A safety run-in substudy investigating the safety, tolerability, PK, and
preliminary efficacy of ociperlimab in combination with tislelizumab in
Japanese patients is planned; preliminary safety and tolerability will be
evaluated before Japanese patients are randomized in this Phase 3 study.
Patients will be required to sign a prescreening informed consent form (ICF) to
undergo prescreening collection of tissue samples (archival tissue or fresh
biopsy) for central evaluation of PD-L1 status. Patients will be required to
sign the main ICF to undergo screening procedures. Approximately 660 patients
will be enrolled in the main study.
Blinding will be accomplished using placebo infusions of normal saline in
Treatment Arms B and C so that all patients will receive 2 infusions on Day 1
of each cycle. Study treatments will be prepared by unblinded pharmacists, who
will mask treatments to ensure that patients and study staff remain blinded.
As of the approval date of protocol amendmnet version 2.0, eligible
participants will be randomized in a 5:5:2 ratio to receive ociperlimab +
tislelizumab (Arm A), pembrolizumab + placebo (Arm B), or tislelizumab +
placebo (Arm C) instead of 5:5:1 as specified in protocol amendment version 1.0.
Study treatments will be given as follows:
• Arm A: Tislelizumab 200 mg intravenously followed by ociperlimab 900 mg
intravenously once every 3 weeks
Note: As of Protocol Amendment Version 3.0, the ociperlimab dose that
will be administered to Japanese patients allocated in Arm A was
determined to be 900 mg based on the results from the safety run-in
substudy
• Arm B: Pembrolizumab 200 mg intravenously followed by placebo intravenously
once every 3 weeks
• Arm C: Tislelizumab 200 mg intravenously followed by placebo intravenously
once every 3 weeks.
All study treatments will be administered until intolerable toxicity,
withdrawal of informed consent, or the timepoint at which, in the opinion of
the investigator, the patient is no longer benefiting from study therapy.
Crossover is not permitted. Treatment beyond the initial
investigator-assessed, RECIST v1.1 defined disease progression is permitted in
all arms if the criteria below are met:
• Absence of clinical symptoms and signs of progressive disease (including
clinically significant worsening of laboratory values)
• Eastern Cooperative Oncology Group (ECOG) Performance Status <= 1
• Absence of rapid progression of disease or of progressive tumor at critical
anatomical sites (eg, spinal cord compression) that requires urgent alternative
medical intervention
• Investigators must obtain written informed consent for treatment beyond
radiologic disease progression and inform patients that this practice is not
considered standard in the treatment of cancer. Patients must be informed that
they may be forgoing treatment that has shown benefit by continuing treatment
beyond progression
• The decision to continue study drug(s) beyond initial investigator-assessed
progression must be agreed with the sponsor medical monitor
Patients who receive study treatment beyond progression will have tumor
assessments performed according to the original schedule until study treatment
discontinuation. Patients will be permanently discontinued from study
treatment if the patient is deemed to meet criteria for RECIST v1.1 defined
disease progression as determined by both the investigator and the BIRC. Tumor
assessments are required to be performed on schedule regardless of whether
study treatment has been administered or held (i.e. their schedule should not
be adjusted for delays in cycles).
Intervention
Study treatments will be given as follows:
• Arm A: Tislelizumab 200 mg intravenously followed by ociperlimab 900 mg
intravenously once every 3 weeks
• Arm B: Pembrolizumab 200 mg intravenously followed by placebo intravenously
once every 3 weeks
• Arm C: Tislelizumab 200 mg intravenously followed by placebo intravenously
once every 3 weeks.
Study burden and risks
There are risks that are not known or do not happen often when patients take
the study treatment. The investigator will inform the patient in a timely
manner of any new information, findings, or changes to the way the research
will be done that might influence your willingness to continue to take part in
this study.
Aeschengraben 27 - 21st Floor Aeschengraben 27
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Basel 4051
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Listed location countries
Age
Inclusion criteria
1.Able to provide written informed consent and can understand and agree to
comply with the requirements of the study and the schedule of assessments.
2.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).
3.Histologically or cytologically documented locally advanced or recurrent
NSCLC that is not eligible for curative surgery and/or definitive radiotherapy
with or without chemoradiotherapy, or metastatic nonsquamous or squamous NSCLC.
4.No prior systemic treatment for metastatic NSCLC. 5.Agreement to provide
archival tissue (formalin-fixed paraffin-embedded block containing tumor
[preferred] or approximately 6 to 15 freshly cut unstained slides) or fresh
biopsy (if archival tissue is not available) for central evaluation of PD-L1
levels and retrospective analysis of other biomarkers. 6.Tumors with PD-L1
expressed in >= 50% tumor cells as determined centrally (or locally in the US
sites). 7.At least 1 measurable lesion as defined per RECIST v1.1. 8.ECOG
Performance Status <= 1. 9.Adequate organ function as indicated by the following
laboratory values during screening: a.Patients must not have required blood
transfusion or growth factor support <= 14 days before sample collection at
Screening for the following: *Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
*Platelets >= 75 x 10^9/L *Hemoglobin >= 90 g/L b.Serum creatinine <= 1.5 x upper
limit of normal (ULN) or estimated Glomerular Filtration Rate >= 60 mL/min/1.73
m2 by Chronic Kidney Disease Epidemiology Collaboration equation (Appendix 8).
Note: for France only: Serum creatinine <= 1.5 x ULN and estimated glomerular
filtration rate or estimated creatinine clearance >= 60 mL/min/1.73 m2 by
CKD-EPI and Cockcroft and Gault equations, respectively (Appendix 8). c.Serum
total bilirubin <= 1.5 x ULN (total bilirubin must be < 3 x ULN for patients
with Gilberts syndrome). d.AST and ALT <= 2.5 x ULN or < 5 x ULN if hepatic
metastases present. 10.Females of childbearing potential must be willing to use
a highly effective method of birth control for the duration of the study, and
for >= 120 days after the last dose of study drug, and must have a negative
urine or serum pregnancy test <= 7 days before randomization. 11.Nonsterile
males must be willing to use a highly effective method of birth control for the
duration of the study and for >= 120 days after the last dose of study drug. •A
sterile male is defined as one for whom azoospermia has been previously
demonstrated in a semen sample examination as definitive evidence of
infertility. •Males with known "low sperm counts" (consistent with
"subfertility") are not to be considered sterile for purposes of this study.
Exclusion criteria
1.Known mutation in a. EGFR gene b. ALK fusion oncogene c. BRAF V600E d. ROS1
2.Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, or any
other antibody or drug specifically targeting T-cell costimulation or
checkpoint pathways. 3.Active leptomeningeal disease or uncontrolled, untreated
brain metastasis. Note: Patients with a history of treated and, at the time of
screening, stable central nervous system (CNS) metastases are eligible,
provided they meet all the following: *Brain imaging at Screening shows no
evidence of interim progression, patient is clinically stable for at least 2
weeks and without evidence of new brain metastases. *Measurable and/or
evaluable disease outside the CNS. *No ongoing requirement for corticosteroids
as therapy for CNS disease; off steroids 3 days before randomization;
anticonvulsants at a stable dose are allowed. *No stereotactic radiation or
whole-brain radiation within 14 days before randomization. 4.Active autoimmune
diseases or history of autoimmune diseases that may relapse. 5.Any active
malignancy <= 5 years before randomization except for the specific cancer under
investigation in this study, those with a negligible risk of metastasis or
death, and any locally recurring cancer that has been treated curatively (eg,
resected basal or squamous cell skin cancer, superficial bladder cancer,
localized prostate cancer, or carcinoma in situ of the cervix or breast). 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 randomization. 7.Uncontrolled
diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or
corrected calcium despite standard medical management or >= Grade 3
hypoalbuminemia <= 14 days before randomization. 8.Uncontrollable pleural
effusion, pericardial effusion, or ascites requiring frequent drainage
(recurrence within 2 weeks of intervention). Patients with symptomatic pleural
effusion are excluded unless the patient undergoes a therapeutic thoracentesis
or has had pleurodesis (more than 2 weeks prior) and has subsequently stable
effusions. 9.History of interstitial lung disease, noninfectious pneumonitis or
uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases,
etc. All patients must undergo an assessment of pulmonary function at Screening
10.Infection (including tuberculosis infection, etc) requiring systemic
antibacterial, antifungal, or antiviral therapy within 14 days before
randomization, or patients who tested positive for COVID-19 antigen by a
licensed test during screening. 11.Untreated chronic hepatitis B or chronic HBV
carriers with HBV DNA > 500 IU/mL (or>2500 copies/mL) at Screening. 12.Patients
with active hepatitis C. 13.Known history of human immunodeficiency virus (HIV)
infection, or if HIV status is unknown, positive HIV test at Screening. 14.Any
major surgical procedure <= 28 days before randomization. Patients must have
recovered adequately from the toxicity and/or complications from the
intervention before randomization. 15.Prior allogeneic stem cell
transplantation or organ transplantation. 16.Any of the following
cardiovascular risk factors: a.Cardiac chest pain, defined as moderate pain
that limits instrumental activities of daily living, <= 28 days before
randomization.b. Symptomatic pulmonary embolism diagnosed <= 28 days before
randomization.c.Any history of acute myocardial infarction <= 6 months before
randomization.d.Any history of heart failure meeting New York Heart Association
(NYHA) Classification III or IV (Appendix 6) <= 6 months before
randomization.e.Any event of ventricular arrhythmia >= Grade 2 in severity <= 6
months before randomization.f.Any history of cerebrovascular accident <= 6
months before randomization.g.Uncontrolled hypertension that cannot be managed
by standard antihypertension medications <= 28 days before randomization.h.Any
episode of syncope or seizure <= 28 days before randomization. 17.A history of
severe hypersensitivity reactions to other monoclonal antibodies or a history
of hypersensitivity to the ingredients of tislelizumab or ociperlimab. 18.Was
administered a live vaccine <= 28 days before randomization. 19.Underlying
medical conditions (including laboratory abnormalities) or alcohol or drug
abuse or dependence that will be unfavorable for the administration of study
drug, or affect the explanation of drug toxicity or AEs, or result in
insufficient or impaired compliance with study conduct. 20.Women who are
pregnant or are breastfeeding. 21. Concurrent participation in another
therapeutic clinical study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-507317-10-00 |
| EudraCT | EUCTR2020-004985-21-NL |
| CCMO | NL76777.031.21 |