Clinical Trials /

Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma

NCT04203901

Description:

CMN-001 is an autologous, tumor antigen-loaded dendritic cell immunotherapy. The active components of CMN-001 are autologous, matured dendritic cells, which have been co-electroporated with both in vitro transcribed (IVT) RNA from an autologous tumor specimen and CD40L RNA. CMN-001 is indicated for treatment of intermediate/poor risk patients with advanced renal cell carcinoma (RCC) in combination with nivolumab plus ipilimumab as first line therapy and in combination with lenvatinib plus everolimus as 2nd line therapy post 1st line failure.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma
  • Official Title: A Phase 2b Randomized Trial of Autologous Dendritic Cell Immunotherapy (CMN-001) Plus Standard Treatment of Advanced Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: CMN-001-1
  • NCT ID: NCT04203901

Conditions

  • Advanced Renal Cell Carcinoma

Interventions

DrugSynonymsArms
CMN-001Combination Arm
Nivolumab+IpilimumabCombination Arm
Lenvatinib+EverolimusCombination Arm

Purpose

CMN-001 is an autologous, tumor antigen-loaded dendritic cell immunotherapy. The active components of CMN-001 are autologous, matured dendritic cells, which have been co-electroporated with both in vitro transcribed (IVT) RNA from an autologous tumor specimen and CD40L RNA. CMN-001 is indicated for treatment of intermediate/poor risk patients with advanced renal cell carcinoma (RCC) in combination with nivolumab plus ipilimumab as first line therapy and in combination with lenvatinib plus everolimus as 2nd line therapy post 1st line failure.

Trial Arms

NameTypeDescriptionInterventions
Combination ArmExperimentalCMN-001 dosing (1x10^7 DC/dose) is initiated at Visit 2 during 1st line therapy and through 2nd line therapy. CMN-001 is administered as 1 dose every 3 weeks for 3 doses (Induction phase), followed by maintenance doses, 1 every 4 weeks for 7 doses (Maintenance phase), followed by booster doses, 1 dose every 12 weeks (Booster phase). 1st line therapy, Nivolumab (3mg/kg) + Ipilimumab (1 mg/kg) will be administered at 3 week intervals for 4 administrations starting at visit 1. Followed by Nivolumab (3 mg/kg) administration every 4 weeks until progression. After progression, 2nd line therapy with lenvatinib (18mg/day) + everolimus (5mg/day) until discontinuation criteria are met.
  • CMN-001
  • Nivolumab+Ipilimumab
  • Lenvatinib+Everolimus
Standard TreatmentActive Comparator1st line therapy, Nivolumab (3mg/kg) + Ipilimumab (1 mg/kg) will be administered at 3 week intervals for 4 administrations starting at visit 1. Followed by Nivolumab (3 mg/kg) administration every 4 weeks until progression. After progression 2nd line therapy with lenvatinib (18mg/day) + everolimus (5mg/day) until discontinuation criteria are met.
  • Nivolumab+Ipilimumab
  • Lenvatinib+Everolimus

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years

          2. Advanced disease histologically assessed as RCC, with predominantly clear cell
             histology

          3. Metastatic disease (measurable or non-measurable) that can be monitored throughout the
             course of study participation per iRECIST

          4. Subjects who are candidates for standard first-line therapy

          5. Time from initial RCC diagnosis to initiation of systemic treatment
             (Nivolumab+Ipilimumab) of <1 year

          6. Karnofsky Performance Status (KPS) ≥ 70%

          7. Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to
             Grade ≤ 1 according to National Cancer Institute (NCI) Common Terminology Criteria for
             Adverse Events (CTCAE) Version 4.0

          8. Adequate hematologic function, as defined by central laboratory values for all three
             of the following criteria:

               1. Absolute neutrophil count (ANC) LLN, and

               2. Platelets 75,000/mm3 or 75.0 x 109/L, and

               3. Hemoglobin (Hgb) 8.0 g/dL

          9. Adequate renal function, as defined by either of the following criteria:

               1. Serum creatinine 1.5 x upper limit of normal (ULN),

               2. OR, if serum creatinine greater than 1.5 x ULN, estimated glomerular filtration
                  rate (eGFR) 30 mL/min

         10. Adequate hepatic function, as defined by both of the following:

               1. Total serum bilirubin 1.5 x ULN

               2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2.5 x ULN or,
                  AST and ALT 5 x ULN if liver function abnormalities are due to underlying
                  malignancy

         11. Adequate coagulation function as defined by either of the following criteria:

               1. INR < 1.5 x ULN

               2. For subjects receiving warfarin or LMWH, the subjects must, in the investigator's
                  opinion, be clinically stable with no evidence of active bleeding while receiving
                  anticoagulant therapy. The INR for these patients may exceed 1.5 x ULN if that is
                  the goal of anticoagulant therapy.

         12. Negative serum pregnancy test for female subjects with reproductive potential, and
             agreement of all male and female subjects of reproductive potential to use a reliable
             form of contraception during the study and for 12 weeks after the last dose of study
             drug

         13. Normal ECG or clinically non-significant finding(s) at Screening, in the
             Investigator's opinion

         14. Able to abstain from taking prohibited drugs, either prescription or non-prescription,
             during the treatment phase of the study

         15. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures

         16. Signed and dated informed consent document indicating that the subject (or legally
             acceptable representative) has been informed of all pertinent aspects of the trial
             prior to enrollment

        Exclusion Criteria:

          1. Prior systemic therapy (including adjuvant or neoadjuvant) of any kind for RCC,
             including immunotherapy, chemotherapy, hormonal, or investigational therapy

          2. Prior history of malignancy within the preceding 3 years, except for adequately
             treated in situ carcinomas or non-melanoma skin cancer, adequately treated early stage
             breast cancer, superficial bladder cancer, and non-metastatic prostate cancer with a
             normal PSA.

          3. History of or known brain metastases, spinal cord compression, or carcinomatous
             meningitis, or evidence of brain or leptomeningeal disease

          4. Patients will be excluded if they have <2 of the following risk factors at Screening:

               1. Time from diagnosis to systemic treatment < 1 year

               2. Hgb < LLN

               3. Corrected calcium > 10.0 mg/dL

               4. KPS < 80%

               5. Neutrophils > ULN

               6. Platelets > ULN

          5. NCI CTCAE Grade 3 hemorrhage < 28 days before Visit 1 (Week 0)

          6. Clinically significant cardiovascular conditions within 3 months prior to
             Randomization, which in the Investigator's opinion prohibits the initiation of
             standard targeted therapy, initiating with sunitinib, including:

               1. Cardiac angioplasty

               2. Myocardial infarction

               3. Unstable angina

               4. Coronary artery by-pass graft or stenting

               5. Class III or IV congestive heart failure (CHF), per NYHA Classification NOTE:
                  Patients with left ventricular ejection fraction (LVEF) < LLN as assessed by
                  either echocardiography or multiple gated acquisition (MUGA) scan, who are
                  asymptomatic and are NOT classified as having NYHA Class III or IV CHF, may be
                  eligible but should be monitored for LVEF changes while on sunitinib therapy as
                  recommended in the current sunitinib prescribing information.

               6. Symptomatic peripheral vascular disease

               7. Cerebrovascular accident (CVA) or transient ischemic attack (TIA)

               8. Symptomatic or uncontrolled pulmonary embolism or deep vein thrombosis (DVT)

               9. Uncontrolled cardiac dysrhythmias of NCI CTCAE Grade ≥ 2, or prolongation of the
                  QTc for males > 450 msec and for females > 470 msec as corrected by either the
                  Fridericia or Bazett formula

              10. Uncontrolled or untreated atrial fibrillation

              11. Poorly controlled hypertension, defined as a systolic blood pressure (SBP), ≥ 150
                  mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg NOTE: Initiation of
                  antihypertensive medication(s) is permitted prior to study entry. Blood pressure
                  must be re-assessed on 2 occasions separated by at least 1 hour. Mean SBP/DBP
                  values must be less than 150/90 for eligibility.

              12. Evidence of active bleeding or a bleeding diathesis at Screening

          7. Significant gastrointestinal abnormalities:

               1. Any history of major resection of the stomach or small bowel with ongoing
                  impaired healing.

               2. Malabsorption syndrome with active symptoms in the Investigator's opinion, within
                  3 months prior to Randomization

               3. Active peptic ulcer, which cannot be appropriately managed in the Investigator's
                  opinion, within 3 months prior to Randomization

               4. Intra-luminal bleeding lesions within 3 months prior to Randomization

               5. History of abdominal fistula or intra-abdominal abscess within 3 months prior to
                  Randomization

          8. Pre-existing thyroid abnormality with thyroid function that cannot be appropriately
             managed with medication, in the Investigator's opinion.

          9. Active autoimmune disease or condition requiring chronic immunosuppressive therapy,
             such as rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, organ
             transplant recipient, etc.

             NOTE: Abnormal laboratory values for autoimmunity markers in the absence of other
             signs/symptoms of autoimmune disease are not exclusionary.

         10. Clinically significant infections, including human immunodeficiency virus (HIV),
             syphilis, and active hepatitis B or C

         11. Current treatment with an investigational therapy on another clinical trial

         12. Pregnancy or breastfeeding

         13. Any serious medical condition or illness considered by the investigator to constitute
             an unwarranted high risk for investigational treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:Patients will be followed for OS until the completion of the study.

Secondary Outcome Measures

Measure:Monitor treatment emergent adverse events between both arms
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:Compare adverse events between both arms
Measure:Progression free survival
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:Progression-free survival from the date of subject randomization as assessed by the investigator per iRECIST. Radiological evidence of progression will be derived from tumor imaging assessments at baseline (Screening, Week 0) and restaging scans at Week 13, 21, 29, 37 then every 12 weeks until progression or study withdrawal.
Measure:Tumor Response
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:To compare tumor responses based on iRECIST between study arms

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:CoImmune

Last Updated

September 23, 2020