Primary CNS tumors MedDRA version: 21.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: BAVENCIO
Product Name: BAVENCIO
Product Code: MSB0010718C
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AVELUMAB
Other descriptive name: Anti PD-L1
Concen
Sponsors
Merck Healthcare KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Are = 2 and 16 years at Scr. 5. Adequate bone marrow function at Scr. ANC must be = 1000/µL. Platelet count must be = 100,000/mm3. Hem must be = 8 g/dL. 6. Adequate renal function: Scr. serum CR must be = 1.5 × upper limit of normal (ULN) or CR clearance > 70 mL/minute if serum creatinine > 1.5 × ULN, according to the Cockcroft-Gault formula or by 24-hour urine collection for creatinine clearance or according to local institutional standard method. 7. Adequate hepatic function Screening total bilirubin must be = 1.5 × ULN for age or direct bilirubin = ULN for age if total bilirubin > 1.5 × ULN for age. Scr. serum AST and ALT must be = 3 × ULN for age. 8. Screening prothrombin time/international normalized ratio (INR) must be = 1.5 × institutional ULN for age. 9. Availability of tissue as FFPE block or a minimum of 10 (preferably 25) unstained tumor slides suitable for PD-L1 expression assessment. Tumor tissue from the most recent biopsy should be submitted, and this should be from a nonirradiated area. 10. A negative serum pregnancy test at Scr for all postmenarchal girls, girls = 10 years of age, or per local or institutional guidelines must be obtained. 11. For participants of childbearing potential: agreement to remain abstinent or use 2 adequate methods of contraception for the duration of study intervention period and at least for 60 days after stopping the study interventions. 12. A fractional shortening = 30% or left ventricular ejection fraction = 50% by echocardiogram or multigated acquisition (MUGA) scan within 28 days of study intervention initiation must be demonstrated. 13. Participants with seizures that are well controlled are eligible and may be on antiepileptic medications, provided the dose of the antiepileptic drug(s) is/are stable. 14. Part. must demonstrate an ability to comply with study prot. 15. Are male and/or female. a. Female participants Are not pregnant or breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential OR If a woman of childbearing potential, use a highly effective contraceptive method (i.e., with a failure rate of < 1% per year), preferably with low user dependency, for the following time periods: Before the first dose of the study intervention(s), if us
Exclusion criteria
Exclusion criteria: 1. Participants with low-grade gliomas, for example but not limited to, subependymal giant cell astrocytoma, pilocytic astrocytoma and WHO Grade 1 tumors. 2. Participants demonstrating evidence of worsening of neurologic deficit within 1 week prior to initiation of study interventions. 3. Participants with bulky tumor 4. Participants are not eligible if they experience uncontrolled seizures 5. Tumor surgeries a. Participants eligible for tumor surgery. b Participants who have received major surgery within 28 days prior to the first dose of study interventions. 6. A history of intracranial hemorrhage/spinal cord hemorrhage within 28 days prior to the first dose of study interventions. 7. Participants require therapeutic anticoagulation. 8. Participants with a history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for investigational drug treatment. 9. Participants with urine protein = 1 g protein/24-hour will be ineligible. 10. Gastrointestinal malabsorption, GI anastomosis, or any other condition that might affect absorption of lenvatinib. 11. Clinically significant cardiovascular or cerebrovascular disease 12. Active hemoptysis (bright red blood of at least 2.5 mL) within 3 weeks prior to the first dose of study interventions. 13. Participants with active hepatitis B or hepatitis C infections. 14. Participants with known human immunodeficiency virus infection. 15. Participants with a serious nonhealing wound, ulcer or bone fracture. 16. The participant has known hypersensitivity to any of the study interventions or any components in their formulations, any history of anaphylaxis, or recent (within 5 months) history of uncontrollable asthma. 17. Prior solid organ transplantation. 18. Severe and/or clinically relevant acute or chronic diseases which, might impair the participant’s tolerance for the study or ability to consistently participate in study procedures. 19. Participants with current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation for the full duration of the study. 20. Pregnancy or breast feeding. 21. Any other active malignancy within the past 2 years of Screening. 22. The participant is affected with an autoimmune disease necessitating steroid therapy or other immunomodulatory therapy within the past 2 years of Screening 23. Known active alcohol or drug abuse. Prior/Concomitant Therapy 24. The participant has received treatment with chemotherapy, differentiation therapy, or other immunotherapy within 3 weeks of study entry. 25. The participant has received prior therapy with anti-PD-1, anti-PD-L1, anti-CTLA4 or CD137 directed therapy. 26. The participant has received prior treatment with lenvatinib or any tyrosine kinase inhibitor. 27. Requirement for daily doses of steroids > 8 mg of methylprednisolone (or equivalent). 28. The participant is experiencing any nonhematologic toxicity from prior treatment that has not resolved to Grade = 1 per (CTCAE) Version 5.0 at Screening. 29. The participant has an active infection necessitating systemic treatment with antibiotics, antifungals, antivirals or steroids within 72 hours of the first dose of study intervention. 30. Prior allogeneic stem cell transplant within the last 5 years. 31. The participant has received any hematopoietic growth factor within 2 weeks of study entry. 32. The participant has received transfusion of packed red blood
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Escalation Part 1 1. To evaluate the safety and tolerability of avelumab + lenvatinib 2. To determine the recommended avelumab and lenvatinib dose for expansion Dose Expansion Part 2 1. To assess efficacy by PFS;Secondary Objective: Dose Escalation Part 1 1. To assess PFS based on Investigator assessments and OS Dose Expansion Part 2 1. To assess the OS Dose Escalation Part 1 and Dose Expansion Part 2 1. To further evaluate the safety and tolerability of avelumab + lenvatinib 2. To assess antitumor activity of avelumab + lenvatinib by ORR and DoR 3. To characterize the PK profile of avelumab and lenvatinib when administered in combination. 4. To characterize the immunogenicity of avelumab in combination with lenvatinib;Primary end point(s): Dose Escalation Part 1 1. Occurrence and severity of CTCAE Grade = 3 TEAEs according to NCI-CTCAE Version 5.0. 2. Occurrence of DLTs Dose Expansion Part 2 1. PFS as assessed by Investigators according to RANO criteria;Timepoint(s) of evaluation of this end point: . | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose Escalation Part 1 1. PFS per RANO criteria Dose Escalation Part 1 and Dose Expansion Part 2 1. Occurrence and severity of any grade TEAEs, treatment-related AEs, AESIs, deaths, and clinically significant changes in laboratory parameters. 2. Confirmed objective response as assessed by Investigators according to RANO criteria 3. DoR according to RANO criteria assessed by Investigator. 4. Overall Survival 5. PK parameters including CEOI, AUC, Ctrough of avelumab; Cmax, tmax, and AUC of lenvatinib of at least a single dose as data permit. 6. Immunogenicity of avelumab as measured by ADA assay;Timepoint(s) of evaluation of this end point: . | — |
Countries
Canada, France, Germany, Korea, Republic of, United States
Contacts
Public ContactCommunication Center
Merck Healthcare KGaA
Outcome results
None listed