Phase II study of Pembrolizumab plus Chemotherapy With Lenvatinib for Malignant pleural mesothelioma

JRCT ID: jRCT2051230209

Registered date:27/03/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Malignant pleural mesothelioma
• Date of first enrollment: 01/04/2024
• Target sample size: 25
• Study type: Interventional
• Intervention(s): In induction treatment, study interventions include oral lenvatinib, 8 mg QD, and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2), and pemetrexed, 500 mg/m2 all given by intravenous (IV) infusion on Day 1 of a 21-day cycle. Lenvatinib, pembrolizumab, carboplatin/cisplatin, and pemetrexed combination treatment will be given for 4-6 cycles, after which participants may receive maintenance treatment with Lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and Pembrolizumab may be given for up to a total of 35 cycles

Outcome(s)

• Primary Outcome: Tumor shrinkage (response rate) (Physician Judgment by Medical Institution, Modified RECIST criteria)

Secondary Outcome

1. Progression-Free survival (Physician Judgment by Medical Institution, Modified RECIST criteria)
2. Overall survival time
3. Tumor shrinkage (disease control rate) (Physician Judgment by Medical Institution, Modified RECIST criteria)
4. Duration of response (Physician Judgment by Medical Institution, Modified RECIST criteria)
5. Best overall response (Physician Judgment by Medical Institution, Modified RECIST criteria)
6. Safety endpoints (adverse events, laboratory tests, vital signs, 12-lead ECG, chest X-ray, ECOG Performance Status)

Key inclusion & exclusion criteria

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

Include criteria

1.Patients with unresectable advanced or metastatic malignant pleural mesothelioma without prior treatment for malignant pleural mesothelioma
2.Patients expected to survive more than 90 days
3.Patients with a transcutaneous oxygen saturation of 94% or greater measured with a pulse oximeter at rest without oxygen inhalation within 7 days prior to enrollment
4.Patients who have given written consent to participate in this clinical trial (consent by a surrogate is also acceptable, if applicable).
5.Patients who are judged by the principal investigator or subinvestigator to have one or more measurable lesions as defined in mRECIST by CT or MRI imaging within 28 days prior to enrollment. However, if the measurable lesion is a pleural lesion only and there is a history of pleurodesis (patients who underwent pleurodesis within 14 days prior to enrollment or pleurodesis with Picibanil within 28 days prior to enrollment are excluded), only patients whose measurable lesion was confirmed on imaging after pleurodesis are eligible.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
7. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of [insert disease under study and any defining characteristics of the disease population] will be enrolled in this study.
8. Have adequate organ function as defined in the following table. All clinical laboratory tests in the screening period should be performed within 10 days prior to the start of study intervention.

Exclude criteria

1. Patients with concomitant or pre-existing severe hypersensitivity reactions to other drugs, including antibody preparations
2. A WOCBP who has a positive urine pregnancy test within 72 hours prior to trial registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Note. in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (for example, CTLA4, OX40, CD137).
4. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to trial registration.
5. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
6. 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.
7. 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 study drug.
8. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
9. Has known active CNS metastases and or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, in other words. 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 requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
10. Has severe hypersensitivity (more than Grade 3) to pembrolizumab and or any of its excipients.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years (in other words, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (for example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
12. Has a history of (non-infectious) pneumonitis interstitial lung disease that required steroids or has current pneumonitis interstitial lung disease.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV) infection.
15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen (HBsAg) reactive or HBV-DNA detected) or known active Hepatitis C virus (defined as HCV RNA (qualitative) detected or HCV antibody reactive, if HCV-RNA is not the local SOC) infection.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participants participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18. Is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
19. Has had an allogenic tissue solid organ transplant.
20. Patients with diverticulitis or symptomatic gastrointestinal ulcer disease
21. Patients with pleural effusions requiring drainage more frequently than once every 2 weeks
22. Patients with pericardial or ascites effusions requiring treatment
23. Patients with uncontrolled tumor-related pain
24. Patients with a history of transient ischemic attack, cerebral vascular attack, thrombosis or thromboembolism (pulmonary artery embolism or deep vein thrombosis) within 180 days prior to registration
Patients with the following unmanageable or serious cardiovascular diseases
Myocardial infarction within 180 days prior to enrollment
Uncontrolled angina pectoris within 180 days prior to enrollment
New York Heart Association (NYHA) Classification of Cardiac Function Classification III or IV congestive heart failure
Uncontrolled hypertension (systolic blood pressure more than 150 mmHg or diastolic blood pressure more than 90 mmHg for more than 24 hours) despite appropriate therapy
Uncontrolled arrhythmia
25. Patients receiving anticoagulation therapy (excluding antiplatelet therapy including low-dose aspirin) or with diseases requiring such therapy
26. Patients with uncontrolled diabetes mellitus
27. Patients undergoing surgical treatment with local or surface anesthesia within 14 days prior to enrollment
28. Patients undergoing surgical treatment involving general anesthesia within 28 days prior to enrollment
29. Patients who underwent pleurodesis within 14 days prior to enrollment
30. Patients who underwent pleurodesis with picivanil within 28 days prior to enrollment
31. Patients who underwent pericardial adhesion within 28 days prior to enrollment
32. Patients who underwent peritoneal adhesions
33. Patients who received radiation therapy for pain relief within 14 days prior to enrollment
34. Patients who have received radiopharmaceuticals (excluding the use of radiopharmaceuticals for laboratory and diagnostic purposes) within 56 days prior to enrollment
35. Patients who have received other unapproved drugs (including approved drugs not indicated for malignant pleural mesothelioma, drugs administered through clinical studies or unapproved combination drugs, or new formulations) within 28 days (90 days for antibody products) prior to enrollment
36.Patients with prolonged QT interval (QTc, corrected by Fridericia's formula) more than 480 msec
37.Participants with proteinuria 1+ or more on urine dipstick testing/urinalysis will undergo24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein more than 1 g/24 hours will be ineligible.
38.Active hemoptysis (bright red blood more than 1/2 teaspoon) or other uncontrolled bleeding within 14 days prior to the study registration.
39.Radiographic evidence of intratumoral caviations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered because for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy. (In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta).

Related Information

• Primary Sponsor: Kuribayashi Kozo
• Source(s) of Monetary Support: MSD K.K.