A Study of Ociperlimab With Tislelizumab Compared to Pembrolizumab in Participants With Untreated Lung Cancer

JRCT ID: jRCT2061210035

Registered date:28/09/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Locally Advanced, Unresectable, or Metastatic Non -Small Cell Lung Cancer
• Date of first enrollment: 15/11/2021
• Target sample size: 72
• Countries of recruitment: China,Japan,Italy,Japan,Korea,Japan,Poland,Japan,Rumania,Japan,Russia,Japan,Spain,Japan,Taiwan,Japan,Turkey,Japan,US,Japan,UK,Japan,France,Japan
• Study type: Interventional

Intervention(s)

1) Safety run in study:
Tislelizumab 200 mg intravenously followed by ociperlimab 900 mg intravenously once every 3 weeks on (Day 1 of each 21-day cycle)
2)Main study:
Tislelizumab 200 mg intravenously followed by ociperlimab 900 mg intravenously once every 3 weeks on (Day 1 of each 21-day cycle)
Pembrolizumab 200 mg intravenously followed by placebo intravenously once every 3 weeks(Day 1 of each 21-day cycle)
Tislelizumab 200 mg intravenously followed by placebo intravenously once every 3 weeks(Day 1 of each 21-day cycle)

Outcome(s)

Primary Outcome

1) Safety run in study:
To investigate the safety and tolerability of ociperlimab in combination with tislelizumab in Japanese patients.
To characterize the pharmacokinetics (PK) of ociperlimab in combination with tislelizumab in Japanese patients.
2)Main study: OS (time from the date of randomization to the date of death due to any cause)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Safety Run In
1.Histologically or cytologically documented locally advanced or metastatic solid tumor for which standard of care treatment in Japan is not available or not tolerated
2.ECOG Performance Status <= 1
3.Adequate organ function as indicated by laboratory values
4.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 C1D1.
5.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.
Main Study
1.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.
2.No prior systemic treatment for metastatic NSCLC.
3.Agreement to provide archival tissue or fresh biopsy for prospective central evaluation of PD-L1 levels and retrospective analysis of other biomarkers
4.Tumors with PD-L1 TC >= 50% expression as centrally determined (or locally in the US and Japan).
5.At least 1 measurable lesion as defined per RECIST v1.1.
6.ECOG Performance Status <= 1.
7.Adequate organ function
8.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.
9.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.

Exclude criteria

Safety run-in part
1. Eligible to receive a standard of care therapy in Japan
2. Has received more than 2 prior systemic therapies for metastatic solid tumors
3. Discontinued prior therapy with an anti-PD-1, anti-PD-L1, anti-programmed cell death ligand-2 (PD-L2), anti-T-cell immunoglobulin and ITIM domain (TIGIT), or any otherantibody or drug specifically targeting T-cell co-stimulation or checkpoint pathway due to serious or => Grade 3 (per NCI-CTCAE v5.0 criteria) immune-related toxicity.
4. Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
5. Active autoimmune diseases or history of autoimmune diseases that may relapse.
6. Any active malignancy <= 2 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast)
7. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication <= 14 days before C1D1
8. 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 C1D1
9. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, etc.
10. Infection (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to C1D1
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 HIV infection
14. Any major surgical procedure <= 28 days before C1D1 or anticipation of need for major surgical procedure during the course of the study. Patients must have recovered adequately from the toxicity and/or complications from the intervention before C1D1.
15. Immunodeficiency, 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 C1D1.
b. Pulmonary embolism <= 28 days before C1D1.
c. Any history of acute myocardial infarction <= 6 months before C1D1.
d. Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV<= 6 months before C1D1.
e. Any event of ventricular arrhythmia => Grade 2 in severity <= 6 months before C1D1.
f. Any history of cerebrovascular accident <= 6 months before C1D1.
g. Uncontrolled hypertension that cannot be managed by standard antihypertension medications <= 28 days before C1D1.
h. Any episode of syncope or seizure <= 28 days before C1D1.
17. A history of severe hypersensitivity reactions to other monoclonal antibodies.
18. Was administered a live vaccine <= 28 days before C1D1
19. Toxicities from prior therapy that have not recovered to baseline, <= Grade 1, or stabilized, except for AEs not considered a likely safety risk
20. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that will be unfavorable for the administration of study drug or that will affect the explanation of drug toxicity or AEs, or result in insufficient or impaired compliance with study conduct.
21. Concurrent participation in another therapeutic clinical study
22. Women who are pregnant or are breastfeeding

Main Study
1.Known mutations in EGFR gene, ALK fusion oncogene,BRAF V600E, ROS1
2. Prior therapy with an anti-PD-1, anti-PD-L1, anti-programmed cell death ligand-2 (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.
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
6. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone 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).
9. History of interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, etc. Patients with significantly impaired pulmonary function or who require supplemental oxygen at baseline 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 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. Pulmonary embolism <= 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. For France only, specify: Systolic pressure => 140 mmHg or diastolic pressure => 90 mmHg on repeated measurements.
h. Any episode of syncope or seizure <= 28 days before randomization.
17. A history of severe hypersensitivity reactions to other monoclonal antibodies.
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 that will 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.

Related Information

• Primary Sponsor: Tsumura Akari
• Secondary ID(s): NCT04746924