JCOG2302: Randomized phase III trial comparing nivolumab therapy and S-1 therapy in the second-line treatment of non-small cell lung cancer with interstitial pneumonitis

JRCT ID: jRCTs031240432

Registered date:25/10/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced non-small cell lung cancer without driver gene alteration
• Date of first enrollment: 25/10/2024
• Target sample size: 180
• Study type: Interventional

Intervention(s)

Group A
S-1 (80-120 mg/body) days 1-14, every 3 weeks for 1 course, up to 1 year from the start of protocol treatment

Group B
Nivolumab (240 mg) day 1, every 2 weeks for 1 course, up to 1 year from the start of protocol treatment

Outcome(s)

• Primary Outcome: Overall Survival
• Secondary Outcome: Progression-free survival, Response rate, Time to exacerbation of ILD (Interstitial Lung Disease), Adverse events, Serious adverse events

Key inclusion & exclusion criteria

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

Include criteria

(1) Cytologically (including biopsy) or histologically confirmed non-small cell lung cancer.
(2) Stage IV, postoperative recurrent disease,
(3) For prior systemic therapy:
(i) No prior S-1 or immune checkpoint inhibitors
(ii) Refractory/intolerant to first-line platinum-based therapy (excluding S-1) for NSCLC
(iii) >=168 days since last non-immune checkpoint inhibitor anticancer drug in neo/adjuvant therapy
(4) Suspected ILD on imaging, meeting all:
(i) No known cause (e.g., collagen disease, drug-induced, sarcoidosis, hypersensitivity pneumonitis)
(ii) Chest CT shows:
(a) No honeycomb sign
(b) HRCT pattern: Probable UIP, Indeterminate for UIP, or Alternative diagnosis (ATS/ERS/JRS/ALAT 2018)
(iii) No history of acute ILD exacerbation
(iv) Antinuclear antibody <80x
(v) %VC >=80%
(vi) If biopsied, not diagnosed as UIP or Probable UIP with honeycomb signs
(5) EGFR mutation negative for non-squamous NSCLC
(6) ALK, ROS1, BRAF(V600E), MET exon 14 skipping, RET, NTRK fusions negative/unknown
(7) Age >=18 at registration
(8) ECOG PS 0-1
(9) Eligible regardless of PD-L1 (22C3) expression.
(10) Measurable lesions not required
(11) No Grade >=3 SVC syndrome, pericardial effusion, pleural effusion, ascites, symptomatic brain metastases, leptomeningeal carcinomatosis, or spinal metastases requiring radiation or surgery
(12)
(i) Palliative radiation for non-CNS metastases: >=7 days (exclude if >30 Gy to thorax within 168 days)
(ii) Stereotactic RT/gamma knife for CNS metastases: >=7 days
(iii) Whole brain RT: >=14 days
(iv) Drainage
(v) Pleurodesis
(vi) Transfusion, hematopoietic factors
(vii) Incisional biopsy, trauma treatment
(viii) Surgery under general anesthesia
(13) No autoimmune diseases
(14) Adequate organ function
(15) Written informed consent

Exclude criteria

(1) Synchronous double or multiple cancer or metachronous double or multiple cancer within 2 years.
(2) Systemic infection requiring treatment
(3) Fever >=38.0 degrees Celsius at registration
(4) During pregnancy, within 28 days of postparturition, or during lactation.
(5) Psychiatric disorders or symptoms interfering with daily life, deemed unsuitable for trial participation
(6) Continuous systemic administration of steroids >10 mg/day prednisolone equivalent or other immunosuppressants
(7) Poorly controlled diabetes despite appropriate treatment
(8) History of cerebrovascular event within 1 year
(9) Two or more transient ischemic attacks
(10) Symptomatic congestive heart failure, unstable angina, or myocardial infarction within 6 months
(11) Clinically serious arrhythmia on the electrocardiogram.
(12) Hypersensitivity to S-1 or nivolumab

Related Information

• Primary Sponsor: Kogure Yoshihito
• Source(s) of Monetary Support: National Cancer Center Japan