First-line CBDCA/PTX/LEN/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas (Artemis)

Inclusion Criteria: 1. 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. 2. 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. Or, in the case of stage III Masaoka-Koga classification, patients who are judged to be incapable of radical resection (R0 resection is not possible due to the combined resection of invasive lesions in surrounding organs (pericardial sac, lung, great vessels, etc.) or who are not eligible for curative treatment with chemoradiotherapy. A history of adjuvant chemotherapy and radiation therapy is acceptable for perioperative adjuvant therapy prior to the finding of recurrence. If platinum-containing cancer chemotherapy has been administered as adjuvant therapy, it is eligible if there is an interval of at least 24 weeks before registration. 3. No symptomatic brain metastases, carcinomatous meningitis, or spinal metastases requiring radiotherapy or surgery 4. No prior history of an antiangiogenetic agent targeting VEGFR for thymic carcinoma 5. Not receiving radiotherapy within 14 days before registration Male participants 6. A male participant must agree to use contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 135 days after the last dose of study treatment and refrain from donating sperm during this period. Female participants: 7. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR 2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment. 8. The participant provides written informed consent for the trial 9. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions 10. Meet the following criteria for Hepatitis B and C Patients with no history of HBV or HCV infection or who meet the following criteria 10.1 Hepatitis B positive subjects Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have an undetectable HBV viral load prior to registration. Participants should remain on anti-viral therapy throughout the study intervention and follow local guidelines for HBV anti-viral therapy post-completion of the study intervention. 10.2 Participants with a history of HCV infection Participants are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to registration. 11. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. 12. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days before registration. 13. Have adequate organ function as defined in the following table (Table 8). Specimens must be collected within 14 days prior to registration. 14. Have a predicted life expectancy of \>12 weeks Exclusion Criteria: 1. Has diagnosed as thymomas 2. Has related immune-related complications such as myasthenia gravis, pure red cell aplasia, or hypogammaglobulinemia 3. Patients with ECG QT correction interval prolongation or history of such prolongation (patients with QTcF \> 480 ms) 4. Has a LVEF below the institutional normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO) 5. A WOCBP who has a positive urine pregnancy test within 72 hours prior to registration (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required 6. Has urine protein ≥1 g/24 hours Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria 7. Has had major surgery within 3 weeks prior to the first dose of study interventions 8. Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability 9. Has any of the following a) to i): 1. History of interstitial pneumonia or evidence of interstitial lung disease 2. Uncontrollable autoimmune disease receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy 3. History or complications of hypertensive crisis or hypertensive encephalopathy 4. Surgery under general anesthesia within 28 days before registration 5. History of total gastrectomy 6. Complication of congenital bleeding predisposition or abnormal coagulation 7. Complication of Grade 3 or higher gastrointestinal or non-gastrointestinal fistula with CTCAE v5.0 8. History of Grade 3 or higher bleeding (site not specified) with CTCAE v5.0 within 28 days prior to registration 9. Blood pressure is not well controlled (with 2 or fewer antihypertensive drugs\* 2, systolic blood pressure is 150 mmHg or less and diastolic blood pressure is 90 mmHg or less) \*Antihypertensive drugs are counted by the number of compounds 10. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. 11. Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib 12. Active hemoptysis (bright red blood of at least 0.5 teaspoons) within 3 weeks prior to the first dose of the study drug 13. Has received prior radiotherapy within 14 days before registration. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease 14. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. Approved COVID-19 vaccines (excluding live vaccines and/or live-attenuated vaccines) are allowed 15. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent 16. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study drug 17. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded 18. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening),clinically stable and without the requirement of steroid treatment for at least 14 days prior to the first dose of the study intervention 19. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients 20. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with the use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed 21. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease 22. Has an active infection requiring systemic therapy 23. Has a known history of Human Immunodeficiency Virus (HIV) infection 24. Concurrent active Hepatitis B ( defined as HBsAg positive and detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection 25. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator 26. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial 27. Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Is expecting to father children within 135 days after the last dose of trial treatment 28. Has had an allogeneic tissue/solid organ transplant