Phase III randomized, placebo-controlled, double-blind, investigator-initiated clinical trial to evaluate the efficacy and safety of TM5614 in combination with nivolumab for the treatment of unresectable, anti-PD-1 antibody refractory malignant melanoma (melanoma)

JRCT ID: jRCT2021240049

Registered date:15/01/2025

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: malignant melanoma
• Date of first enrollment: 01/02/2025
• Target sample size: 124
• Study type: Interventional

Intervention(s)

TM5614 or placebo and nivolumab in 4-week cycles until criteria for discontinuation are met or up to 12 cycles
Investigational drug TM5614 or placebo will be taken 3 tablets (180 mg for TM5614) once a day after breakfast.
Concomitant drug Nivolumab will be continued at a dose of 240 mg every 2 weeks or 480 mg every 4 weeks.

Outcome(s)

• Primary Outcome: Overall survival

Secondary Outcome

Overall survival rate (1, 2, 3 years)
Objective response rate (RECIST evaluation)
Disease control rate
Progression-free survival
Duration of response

Key inclusion & exclusion criteria

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

Include criteria

(1) Patients 18 years of age or older
(2) Patients who have given written consent to participate in this study
(3) Patients with unresectable malignant melanoma or stage III/IV melanoma, for whom nivolumab administration is deemed appropriate by the investigator
(4) Patients with at least one evaluable lesion as defined in the RECIST Guidelines Version 1.1 on imaging within 28 days prior to the start of treatment with the investigational drug
(5) Patients who have been treated with nivolumab plus ipilimumab, nivolumab, or pembrolizumab alone and who have progressed. For nivolumab or pembrolizumab administered perioperatively or after radical radiotherapy, patients who relapsed during treatment or within 168 days after the last administration are included. For patients with BRAF mutation-positive disease, patients who have been further treated with BRAF/MEK inhibitors and who have progressed.
(6) Patients with ECOG PS of 0-1
(7) Patients expected to be alive for at least 90 days at the time of consent
(8) Patients taking less than 10 mg/day of prednisolone-equivalent steroid medication
(9) Women of childbearing potential (including patients without menstruation for medical reasons such as chemical menopause) who have agreed to use double contraception from the time of consent for at least 5 months after the last dose of study drug. In addition, patients who agree not to breastfeed for at least 5 months after the last dose of nivolumab from the date of consent. For males, patients who have agreed to use contraception from the time of consent for at least 7 months after the last dose of study drug.
(10) Patients whose most recent clinical laboratory tests performed within 7 days (same day of the week is acceptable) prior to enrollment in this study meet the following criteria. The laboratory values must not have received granulocyte colony stimulating factor (G-CSF) administration or blood transfusion within 14 days prior to the date of examination.
-White blood cell count greater than 2,000/mm3
-Neutrophil count greater than or equal to 1,500/mm3
-Platelet count greater than or equal to 100,000/mm3
-Hemoglobin greater than or equal to 7.5 g/dL
-AST and ALT are 3 times or less than the upper limit of the reference value of the implementing medical institution (however, 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 (measured value or estimated value by Cockcroft/Gault formula) is 45 mL/min or more.

Exclude criteria

(1) Patients with a concomitant severe hypersensitivity reaction or history of hypersensitivity reactions to other antibody products
(2) Patients with residual adverse effects from previous treatment or surgical therapy that the investigator (subinvestigator) determines will affect the safety evaluation of the investigational drug.
(3) Patients with concomitant autoimmune diseases or a history of chronic or recurrent autoimmune diseases. However, patients with hypothyroidism that can be managed by hormone replacement therapy or with concomitant skin diseases that do not require systemic therapy (vitiligo, psoriasis, alopecia, etc.) may be enrolled.
(4) Patients with multiple cancers (patients with completely resected basal cell carcinoma, intraepithelial carcinoma, intramucosal carcinoma or superficial bladder cancer, or other cancers that have not recurred for at least 5 years prior to obtaining consent may be enrolled)
(5) Patients with metastasis in more than 3 organs.
(6) Patients with central nervous system metastasis. However, patients who are asymptomatic and do not require treatment may be enrolled.
(7) Patients with interstitial lung disease, pulmonary fibrosis, or radiation pneumonitis diagnosed by diagnostic imaging. However, patients with radiation pneumonitis who are confirmed to be stabilized by fibrosis and have no concern of relapse may be enrolled.
(8) Patients with complicated diverticulitis or symptomatic gastrointestinal ulcer disease
(9) Patients with pericardial, pleural, or ascites effusions requiring continuous treatment
(10) Patients with stable and uncontrolled tumor-related pain
(11) Patients with a history of transient ischemic or cerebrovascular attack within 180 days prior to enrollment in this study
(12) Patients with a history of severe thrombosis or thromboembolism such as pulmonary artery embolism or deep vein thrombosis. However, patients who have had a history of thrombosis or thromboembolism for at least 90 days and have no concerns about recurrence may be enrolled.
(13) Patients who have participated in other clinical trials within 30 days prior to enrollment.
(14) Patients with a history of hypersensitivity to nivolumab
(15) Patients with the following cardiovascular diseases
Patients with a history of myocardial infarction in the 6 months prior to enrollment
Patients with symptomatic arrhythmia requiring treatment
(16) Patients who received radiation therapy within 28 days prior to enrollment in this study. However, irradiation for palliative purposes prior to 15 days prior to enrollment is acceptable.
(17) Patients who have received radiopharmaceuticals (excluding the use of radiopharmaceuticals for laboratory and diagnostic purposes) within 56 days prior to enrollment in this study.
(18) Patients with a positive HIV antibody test, HBs antigen test, or HCV antibody test. (However, if the HBs antigen test is positive but HBV-DNA quantification is below the limit of detection*, or if the HCV antibody test is positive but the patient does not have active hepatitis C, the patient may be enrolled.)* These patients should be carefully monitored and given prophylactic antiviral drugs in accordance with hepatitis B guidelines.
(19) Patients with bleeding tendency
(20) Pregnant, lactating, or possibly pregnant patients
(21) Patients with systemic infections requiring treatment
(22) Patients with uncontrolled diabetes mellitus
(23) Patients requiring transplantation therapy or with a history of transplantation therapy (excluding autologous transplantation)
(24) Patients who are judged to lack the capacity to consent due to complications such as dementia
(25) Other patients who are judged by the investigator (subinvestigator) to be ineligible for this clinical trial.

Related Information

• Primary Sponsor: Fujimura Taku
• Source(s) of Monetary Support: Renascience Inc.