Phase II study of combination treatment of nivolumab and TM5614 for non-small cell lung cancer (TM-Uprise Study)

JRCT ID: jRCT2061230039

Registered date:19/07/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: non-small cell lung cancer
• Date of first enrollment: 01/09/2023
• Target sample size: 39
• Study type: Interventional
• Intervention(s): Patients will receive intravenous nivolumab (240 mg every 2 weeks or 480 mg every 4 weeks) and oral administration of TM5614 (120 mg every day, in the absence of serious adverse events during the first 4 weeks, increasing the dose from 120 mg to 180 mg), until they experience radiologic disease progression, treatment-related adverse events of unacceptable severity, withdrawal of consent, or termination of treatment at the discretion of the investigator.

Outcome(s)

• Primary Outcome: The objective response rate

Secondary Outcome

- Progression-free survival
- Overall survival
- Disease control rate
- Duration of response
- Adverse event rate

Key inclusion & exclusion criteria

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

Include criteria

(1) Age of >=18 years at the time of informed consent
(2) Provision of written informed consent
(3) Histologically confirmed stage III with no indication for curative surgery, radiotherapy, stage IV, or recurrent NSCLC
(4) No sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements in patients with non-squamous carcinoma
(5) No or unknown ROS-1 rearrangement, BRAF (V600E) gene mutation, MET exon 14 skipping mutation, RET rearrangement, or NTRK rearrangement.
(6) Disease progression during or after the most recent treatment and history of treatment
- Platinum doublet chemotherapy
- Immune checkpoint inhibitors (e.g. nivolumab, pembrolizumab, atezolizumab, nivolumab, and ipilimumab)
- Chemotherapy (e.g. pemetrexed, docetaxel, nab-paclitaxel, S-1)
(7) Measurable lesions based on Response Evaluation Criteria in Solid Tumors (RECIST) Ver.1.1
(8) Eastern Cooperative Oncology Group performance status of 0-1
(9) Estimated life expectancy of >=90 days
(10) Adequate organ function within 7 days prior to registration. The laboratory values must not have received granulocyte colony stimulating factor (G-CSF) administration or blood transfusion within 14 days prior to the test.
- Neutrophil count greater than 1,500/mm3
- Platelet count greater than 100,000/mm3
- Hemoglobin is 8.5 g/dL or higher
- AST and ALT less than or equal to 3 times the upper limit of the reference value of the medical institution performing the procedure.
If the patient has liver metastasis, AST and ALT are 5 times or less than the upper limit of the reference value of the implementing medical institution.
- Total bilirubin is 2 times or less than the upper limit of the reference value at the institution.
- Creatinine is 1.5 mg/dL or less, or creatinine clearance is 45 mL/min or more as measured or estimated by Cockcroft/Gault formula.
- SpO2 greater than 90% (room air)

Exclude criteria

(1) Active autoimmune disease that has required systemic treatment using corticosteroids or other immunosuppressive medication.
(2) History of serious immune-related adverse events caused by anti-PD-1/anti-PD-L1 antibodies.
(3) Patients receiving continuous systemic administration (oral or intravenous) of steroids or other immunosuppressive drugs exceeding 10 mg/day of prednisolone equivalent.
(4) Multiple cancers.
(5) Central nervous system metastases (symptomatic or requiring treatment).
(6) Carcinomatous meningitis.
(7) Evidence of interstitial pneumonia , Pulmonary fibrosis , Radiation pneumonitis.
(8) Uncontrollable pleural effusion, ascites, or pericardial fluid.
(9) Patients with stable and uncontrolled tumor-related pain.
(10) Patients who have received external-beam or whole-brain irradiation of metastases within 14 days prior to enrollment.
(11) Patients with bleeding tendency.
(12) Patients with systemic infections requiring treatment.
(13) Patients with uncontrolled diabetes mellitus.

Related Information

• Primary Sponsor: Hattori Noboru
• Source(s) of Monetary Support: Renascience Inc.