A phase II, investigator-initiated, non-randomized, open-label, single-arm, multicenter study to evaluate the efficacy and safety of Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab combination for previously untreated advanced or recurrent thymic carcinomas
Patients aged 18 years or older at the time of informed consent, who are pathologically (histologically or cytologically) diagnosed with thymic carcinoma for primary or metastatic thymic lesions, are included. They are preferred to be positive for CD5 or c-KIT by immunohistochemical staining. For those with non-squamous epithelial carcinoma negative for p40 or p63, non-primary cases should be excluded based on their clinical and pathological findings. In addition, those with thymoma are excluded.
Patients with unresectable advanced thymic carcinoma (equivalent to stage IVa or IVb of Masaoka-Koga classification), metastatic or recurrent, who have not been treated with systemic cancer chemotherapy.
No symptomatic brain metastases, carcinomatous meningitis, or spinal metastases requiring radiotherapy or surgery
No prior history of an antiangiogenetic agent targeting VEGFR for thymic carcinoma
Has diagnosed as thymomas
Has related immune-related complications such as myasthenia gravis, pure red cell aplasia, or hypogammaglobulinemia
Patients with ECG QT correction interval prolongation or history of such prolongation (patients with QTcF > 480 ms)
Has a LVEF below the institutional normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
Single group
MK-3475
DrugPembrolizumab will be administered at a dose of 200 mg by intravenous infusion every 21 days (3 weeks) for up to 35 cycles.
Lenvatinib
DrugLenvatinib will be administered at a dose of 8 mg orally QD every 21 days (3 weeks) for up to 4 cycles in the induction phase, followed by 20 mg QD for up to 31 cycles in the maintenance phase. Then, further maintenance therapy with lenvatinib will be allowed until progression or unacceptable adverse events.
Carboplatin
DrugCarboplatin will be administered at a dose of AUC 5 intravenously every 21 days (3 weeks) for up to 4 cycles in the induction phase.
Paclitaxel
DrugPaclitaxel will be administered at a dose of 175 mg/m\^2 intravenously every 21 days (3 weeks) for up to 4 cycles in the induction phase.
Response Rate (RR) by the Blinded independent review committee
RR is defined as the proportion of patients with the best overall response to complete response (CR) or partial response (PR) as evaluated by the independent review committee according to RECIST 1.1
Progression-free survival (PFS)
The registration date shall be the starting date, and the period up to the earlier of date determined to be progression or the date of death due to any cause.
Overall Survival Rate (OS)
The period from the registration date to the date of death due to any cause.
Duration of response (DoR)
The progression-free survival rate at 1 year and 2nd year, and median DoR are calculated using the Kaplan-Meier method. The 95% confidence interval for the progression-free survival rate at 1 year and 2nd year is calculated using Greenwood's formula. The 95% confidence interval for the median DoR is determined using the Brookmeyer and Crowley method.
Adverse event rate
In the safety analysis target population, the frequency of the worst grade in all cycles according to the CTCAE v5.0 Japanese translation JCOG version is calculated for each adverse event and discontinuation by adverse events due to protocol treatment.
Click on the lead sponsor to view all of their trials.
National Cancer Center, Japan
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
