NCT03635892
Active, not recruiting
Phase 2
A Phase 2 Open-Label Study of Nivolumab Combined With Cabozantinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma (CA209-9KU)
ConditionsAdvanced or Metastatic Non-clear Cell Renal Cell CarcinomaUnclassified Renal Cell CarcinomaPapillary Renal Cell CarcinomaFumarate Hydratase Deficient Renal Cell CarcinomaSuccinate Dehydrogenase Deficient Renal Cell CarcinomaCollecting Duct Renal Cell CarcinomaChromophobe Renal Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- cabozantinib
- Conditions
- Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 60
- Locations
- 7
- Primary Endpoint
- objective response rate
- Status
- Active, not recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
The purpose of this study is to compare any good and bad effects of using a combination of nivolumab (Opdivo®) and cabozantinib (Cabometyx®) in people with metastatic kidney cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed and dated IRB-approved Informed Consent Form
- •Pathologic or histologically confirmed unresectable advanced or metastatic nccRCC
- •0 or 1 prior systemic therapies, including treatment in the adjuvant setting
- •Availability of a representative formalin fixed, paraffin embedded tumor specimen or fresh frozen tissue specimen that enables the definitive diagnosis of RCC, accompanied by an associated pathology report. Specimens can be collected by surgical resection or biopsy of the primary tumor or biopsy or resection of a metastatic lesion.
- •Measurable disease, as defined by RECIST 1.1
- •Age ≥18 years
- •Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless adverse events (AE(s)) are clinically nonsignificant and/or stable on supportive therapy.
- •Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
- •ANC ≥ 1500 cells/μL (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
- •WBC counts ≥ 2500/μL and ≤ 15,000/μL without G-CSF
Exclusion Criteria
- •Prior treatment with an immunotherapy agent including high dose IL-2, anti-CTLA-4, anti-PD1, and anti-PD-L1 agents
- •Prior treatment with cabozantinib for non-clear cell RCC
- •Receipt of any type of small molecule kinase inhibitor within 2 weeks of treatment.
- •Receipt of any type of anti-cancer antibody, cytotoxic anticancer therapy, or any other investigational agents within 4 weeks of treatment start
- •Known malignancies of the brain or spinal cord or leptomeningeal disease
- •Patients requiring pain medication must be on a stable regimen at study entry
- •Systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroids \> 10 mg daily prednisone equivalents are allowed in the absence of autoimmune disease
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- •Uncontrolled hypercalcemia (≥ 1.5 mmol/L ionized calcium or Ca ≥ 12 mg/dL or corrected serum calcium ≥ ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
- •Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy
Arms & Interventions
Cohort 1: Unclassified, papillary, and HL RCC
Cohort 1 is designed as a single stage study with a total sample size of 20. This design discriminates between ORR rates of 10 and 35%.
Intervention: cabozantinib
Cohort 1: Unclassified, papillary, and HL RCC
Cohort 1 is designed as a single stage study with a total sample size of 20. This design discriminates between ORR rates of 10 and 35%.
Intervention: nivolumab
Cohort 2: Chromophobe RCC
Cohort 2 is designed as a Simon's optimal two-stage design with a total possible sample size of 17. This design discriminates between ORR rates of 5 and 25%.
Intervention: cabozantinib
Cohort 2: Chromophobe RCC
Cohort 2 is designed as a Simon's optimal two-stage design with a total possible sample size of 17. This design discriminates between ORR rates of 5 and 25%.
Intervention: nivolumab
Cohort 3: Unclassified, papillary, and HL RCC
Cohort 3 is designed as an expansion cohort of Cohort 1 with 20 additional patients to obtain a more precise estimate of the ORR and clinical outcomes
Intervention: cabozantinib
Cohort 3: Unclassified, papillary, and HL RCC
Cohort 3 is designed as an expansion cohort of Cohort 1 with 20 additional patients to obtain a more precise estimate of the ORR and clinical outcomes
Intervention: nivolumab
Cohort 4: Unclassified, papillary, and HL RCC
Cohort 4 is an expansion of Cohorts 1+3, which will accure an additional 40 patients
Intervention: cabozantinib
Cohort 4: Unclassified, papillary, and HL RCC
Cohort 4 is an expansion of Cohorts 1+3, which will accure an additional 40 patients
Intervention: nivolumab
Outcomes
Primary Outcomes
objective response rate
Time Frame: 2 years
per RECIST v1.1
Study Sites (7)
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Related News
KEYNOTE-B61 Demonstrates Robust Data for Non-Clear Cell Renal Cell Carcinoma Treatment- The KEYNOTE-B61 trial, investigating pembrolizumab plus lenvatinib, shows more robust data than the CA-209 9KU trial for non-clear cell renal cell carcinoma (non-ccRCC).
- KEYNOTE-B61 enrolled 158 patients with various non-ccRCC subtypes, reporting a median PFS of 18 months, providing more reliable findings due to its larger sample size.
- While nivolumab plus cabozantinib remains a viable option, KEYNOTE-B61's pembrolizumab plus lenvatinib has emerged as a preferred treatment for many oncologists treating non-ccRCC.
- Cross-trial comparisons are unreliable due to differences in baseline patient populations, but KEYNOTE-B61 offers narrow confidence intervals and broader representation of histologic subtypes.IO/TKI Combinations Show Promise in Non-Clear Cell Renal Cell Carcinoma- Pembrolizumab plus lenvatinib demonstrated a 50% overall response rate in treatment-naive non-clear cell RCC, leading to FDA approval and NCCN recommendation.
- Cabozantinib plus nivolumab showed a 54% overall response rate in a phase 2 trial, supporting its use in non-clear cell RCC, even with prior therapy in some patients.
- Both IO/TKI combinations exhibit manageable adverse event profiles, with common toxicities including hypertension, diarrhea, and hand-foot syndrome.
- Dose adjustments and interruptions are crucial for managing toxicities and maintaining patients on treatment, potentially improving long-term outcomes.IO/TKI Doublets Emerge as Standard of Care in Non-Clear Cell Renal Cell Carcinoma- Phase 2 trials show that IO/TKI combinations, like lenvatinib plus pembrolizumab, demonstrate efficacy in non-clear cell renal cell carcinoma (non-ccRCC) with manageable safety profiles.
- KEYNOTE-B61 trial reported a 51% objective response rate (ORR) in non-ccRCC patients treated with lenvatinib and pembrolizumab, supporting NCCN guideline recommendations.
- Cabozantinib plus nivolumab also shows promise, with a 48% ORR in a phase 2 trial, establishing IO/TKI doublets as effective first-line options for non-ccRCC.
- Treatment decisions should consider patient preference and individual data interpretation, according to Dr. Moshe Ornstein from Cleveland Clinic.