A Study to Assess Dendritic Cell Immunotherapy Plus Standard-of-Care to Treat Advanced Renal Cell Carcinoma

Overview

About this study

The purpose of this study is to evaluate CMN-001 in a randomized trial between standard-of-care (SOC) (first line ipilimumab+nivolumab followed by second line lenvatinib+everolimus) with or without CMN-001.

 

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age ≥ 18 years.
  • Advanced disease histologically assessed as RCC, with predominantly clear cell histology.
  • Metastatic disease (measurable or non-measurable) that can be monitored throughout the course of study participation per iRECIST.
  • Time from initial RCC diagnosis to initiation of randomized study treatment of <1 year
  • Subjects who are candidates for standard first-line therapy initiating wtih nivolumab + ipilimumab.
  • Subjects who have initiated first line therapy with nivolumab + ipilimumab within 3 months of Randomization are eligible for the treatment study if all of the following conditions are met:
    • Has no documented Disease Progression per RECIST 1.1 since initiation of nivolumab + ipilimumab
    • Has not had a decline of KPS ≥ 20% since initiation of nivolumab + ipilimumab
    • Is judged by the investigator to be tolerating nivolumab + ipilimumab
  • KPS  ≥ 70%
  • ≥2 or Heng risk factors are present
  • Prior or concurrent malignancy whose natural history or treatment do not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
  • 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 5.0.
  • Tumor specimen submitted to and assessed by CoImmune as having suitable tumor supporting potential for CMN-001 production
  • Adequate hematologic function, as defined by central laboratory values for all three of the following criteria:
    • Absolute neutrophil count (ANC) LLN; and
    • Platelets 75,000/mm^3 or 75.0 x 10^9/L; and
    • Hemoglobin (Hgb) 8.0 g/dL.
  • Adequate renal function, as defined by either of the following criteria:
    • Serum creatinine 1.5 x upper limit of normal (ULN); OR
    • If serum creatinine greater than 1.5 x ULN, estimated glomerular filtration rate (eGFR) 30 mL/min.
  • Adequate hepatic function, as defined by both of the following:
    • Total serum bilirubin 1.5 x ULN;
    • 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.
  • Adequate coagulation function as defined by either of the following criteria:
    • INR < 1.5 x ULN;
    • 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.
  • 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.
  • Normal ECG or clinically non-significant finding(s) at Screening, in the Investigator's opinion.
  • Able to abstain from taking prohibited drugs, either prescription or non-prescription, during the treatment phase of the study.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • 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:

  • Prior systemic therapy for RCC, including immunotherapy, chemotherapy, hormonal, or investigational therapy, except standard first line therapy with nivolumab + ipilimumab per Treatment Study Inclusion Criterion 6.
  • Prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
  • History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of brain or leptomeningeal disease
  • Patients will be excluded if they have < 2 of the following risk factors at Screening:
    • Time from diagnosis to systemic treatment < 1 year;
    • Hgb < LLN;
    • Corrected calcium > 10.0 mg/dL;
    • KPS < 80%;
    • Neutrophils > ULN;
    • Platelets > ULN.
  • NCI CTCAE Grade 3 hemorrhage < 28 days before Visit 1.
  • Clinically significant cardiovascular conditions within 3 months prior to Randomization, which in the Investigator’s opinion prohibits the initiation of standard therapy, including:
    • Cardiac angioplasty;
    • Myocardial infarction;
    • Unstable angina;
    • Coronary artery by-pass graft or stenting;
    • Class III or IV congestive heart failure (CHF), per NYHA Classification;
    • Symptomatic peripheral vascular disease;
    • Cerebrovascular accident (CVA) or transient ischemic attack (TIA);
    • Symptomatic or uncontrolled pulmonary embolism or deep vein thrombosis (DVT);
    • 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;
    • Uncontrolled or untreated atrial fibrillation;
    • 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 < 150/90 for eligibility;
    • Evidence of active bleeding or a bleeding diathesis at Screening.
  • Significant gastrointestinal abnormalities:
    • Any history of major resection of the stomach or small bowel with ongoing impaired healing;
    • Malabsorption syndrome with active symptoms, which would significantly impair the aborption of permitted oral therapies in the Investigator’s opinion, within 3 months prior to Randomization;
    • Active peptic ulcer, which cannot be appropriately managed in the Investigator’s opinion, within 3 months prior to Randomization;
    • Intra-luminal bleeding lesions within 3 months prior to Randomization;
    • History of abdominal fistula or intra-abdominal abscess within 3 months prior to Randomization.
  • Pre-existing thyroid abnormality (excluding Hashimoto’s disease) with thyroid function that cannot be appropriately managed with medication, in the Investigator’s opinion.
  • Active autoimmune disease or condition (excluding Sjogren’s syndrome) 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.
  • Clinically significant infections, including human immunodeficiency virus (HIV), syphilis, and active hepatitis B or C.
  • Current treatment with an investigational therapy on another clinical trial.
  • Pregnancy or breastfeeding.
  •  Any serious medical condition or illness considered by the investigator to constitute an unwarranted high risk for investigational treatment.

Eligibility last updated 12/22/21. Questions regarding updates should be

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Bradley Leibovich, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
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CLS-20520964

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