Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma

NCT04203901 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: CMN-001-1
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Advanced Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Patients will be followed for OS until the completion of the study.

  Through study completion, an average of 2 years

Secondary Outcomes (3)

• Monitor treatment emergent adverse events between both arms

  Through study completion, an average of 2 years

• Progression free survival

  Through study completion, an average of 2 years

• Tumor Response

  Through study completion, an average of 2 years

Study Arms (2)

Combination Arm

EXPERIMENTAL

CMN-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.

Biological: CMN-001; Biological: Nivolumab+Ipilimumab; Drug: Lenvatinib+Everolimus

Standard Treatment

ACTIVE COMPARATOR

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.

Biological: Nivolumab+Ipilimumab; Drug: Lenvatinib+Everolimus

Interventions

CMN-001 BIOLOGICAL

Autologous Dendritic Cell Therapy

Combination Arm

Nivolumab+Ipilimumab BIOLOGICAL

anti-PD-1 and anti-CTLA4 antibodies

Combination Arm; Standard Treatment

Lenvatinib+Everolimus DRUG

TKI+mTOR inhibitors

Combination Arm; Standard Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Subjects who are candidates for standard first-line therapy
• Time from initial RCC diagnosis to initiation of systemic treatment (Nivolumab+Ipilimumab) of \<1 year
• Karnofsky Performance Status (KPS) ≥ 70%
• 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
• 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/mm3 or 75.0 x 109/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:

You may not qualify if:

• 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.
• 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 (Week 0)
• 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:
• Cardiac angioplasty
• Myocardial infarction
• Unstable angina
• Coronary artery by-pass graft or stenting

Sponsors & Collaborators

• CoImmune: lead

Study Sites (9)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

West Virginia University Cancer Institute

Morgantown, West Virginia, 26506, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 18, 2019
• Study Start: July 22, 2020
• Primary Completion: September 28, 2023
• Study Completion: September 28, 2023
• Last Updated: October 2, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)