JCOG2007: A Multicenter Randomized Phase III Study comparing Pembrolizumab + Platinum Combination Chemotherapy with Nivolumab + Ipilimumab + Platinum Combination Chemotherapy for Treatment-naive Advanced Non-Small Cell Lung Cancer without Driver Gene alteration

JRCT ID: jRCTs031210013

Registered date:06/04/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Treatment-naive advanced non-small cell lung cancer without driver gene alteration
• Date of first enrollment: 09/04/2021
• Target sample size: 422
• Study type: Interventional

Intervention(s)

Group A
(1) Non-squamous NSCLC
CBDCA AUC 5 (day 1) + Pemetrexed 500 mg/m2 (day 1) + Pembrolizumab 200 mg/body (day 1), every 3 weeks, up to 4 cycles
Pemetrexed 500 mg/m2 (day 1) + Pembrolizumab 200 mg/body (day 1), every 3 weeks, up to 2 years
(2) Squamous NSCLC
[1] CBDCA AUC 6 (day 1) + nab-Paclitaxel 100 mg/m2 (day 1, 8, 15) + Pembrolizumab 200 mg/body (day 1), every 3 weeks, up to 4 cycles
Pembrolizumab 200 mg/body (day 1), every 3 weeks, up to 2 years
[2] CBDCA AUC 6 (day 1) + Paclitaxel 200 mg/m2 (day 1) + Pembrolizumab 200 mg/body (day 1), every 3 weeks, up to 4 cycles
Pembrolizumab 200 mg/body (day 1), every 3 weeks, up to 2 years

Group B
(1) Non-squamous NSCLC
CBDCA AUC 5 (day 1) + Pemetrexed 500 mg/m2 (day 1) + Nivolumab 360 mg/body (day 1) + Ipilimumab 1 mg/kg (day 1), every 3 weeks, up to 2 cycles (Ipilimumab given every 6 weeks)
Nivolumab 360 mg/body (day 1) + Ipilimumab 1 mg/kg (day 1), every 3 weeks, up to 2 years (Ipilimumab given every 6 weeks)
(2) Squamous NSCLC
CBDCA AUC 6 (day 1) + Paclitaxel 200 mg/m2 (day 1) + Nivolumab 360 mg/body (day 1) + Ipilimumab 1 mg/kg (day 1), every 3 weeks, up to 2 cycles (Ipilimumab given every 6 weeks)
Nivolumab 360 mg/body (day 1) + Ipilimumab 1 mg/kg (day 1), every 3 weeks, up to 2 years (Ipilimumab given every 6 weeks)

Outcome(s)

• Primary Outcome: Overall Survival
• Secondary Outcome: Overall survival of patients with PD-L1 Tumor proportion score (TPS) <1%, Progression-free survival, Duration of response, Response proportion, Area under the survival curve from registration until 3 years later(restricted mean survival time: RMST), Adverse events, Serious adverse events, Quality of Life (Patient Reported Outcome)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Cytologically (including biopsy) or histologically confirmed non-small cell lung cancer.
(2) Clinical stage III without indication of definitive thoracic radiotherapy, stage IV, postoperative recurrent disease, or recurrence after radiation therapy.
(3) No prior systemic chemotherapy.
(4) No prior drug therapy that specifically target the T cell co-stimulation or checkpoint pathway, such as anti-PD-1 antibody, anti-PD-L1 antibody, and anti-CTLA-4 antibody.
(5) No EGFR gene mutations for non-squamous cell carcinoma.
(6) Negative or unknown ALK fusion gene, ROS1 fusion gene, BRAF (V600E) gene mutation, MET exon 14 skipping mutation, RET fusion gene, or NTRK fusion gene.
(7) Over 20 years old.
(8) Performance status 0 or 1.
(9) Eligible regardless of PD-L1 (22C3) expression.
(10) Measureable or non-measureable.
(11)
(i) No prior palliative radiation therapy for non-central nervous system metastases within 7 days
(ii) No prior stereotactic irradiation and Gamma-knife for central nervous system metastases within 7 days
(iii) No prior whole-brain irradiation within 14 days
(iv) No prior pleural drainage within 7 days
(v) No prior surgery with general anesthesia within 14 days
(12) No symptomatic brain metastasis, leptomeningeal metastasis, or spinal cord metastasis requiring radiotherapy or surgical operation.
(13) No active autoimmune disease.
(14) No findings suggestive of interstitial lung disease or pulmonary fibrosis on the chest computed tomography.
(15) Adequate organ funcion.
(16) Written informed consent for this study.
(17) Written informed consent for pretreatment stool collection for ancillary studies.

Exclude criteria

(1) Synchronous double or multiple cancer or metachronous double or multiple cancer within 2 years.
(2) Infectious disease requiring systemic treatment.
(3) Pyrexia of 38 degrees centigrade or higher.
(4) During pregnancy, within 28 days of postparturition, or during lactation.
(5) Psychological disorder difficult to participate in this clinical study.
(6) Receiving continuous systemic corticosteroid or immunosuppressant treatment.
(7) Diabetes mellitus uncontrollable with the appropriate treatment.
(8) History of stroke within 1 year or frequent transient ischemic attacks.
(9) Symptomatic congestive heart failure, unstable angina, or a history of myocardial infarction within 6 months.
(10) Clinically serious arrhythmia on the electrocardiogram.
(11) Positive for serum hepatitis B surface antigen.
(12) HIV antibody positive.
(13) Grade 2 or higher peripheral neuropathy.
(14) Hypersensitivity to the ingredients / additives of carboplatin, pemetrexed, paclitaxel, nab-paclitaxel, pembrolizumab, nivolumab, and ipilimumab.

Related Information

• Primary Sponsor: OKAMOTO Isamu
• Source(s) of Monetary Support: National Cancer Center Japan,Japan Agency for Medical Research and Development