The aim of this Phase 2 study is to evaluate the efficacy and safety of nivolumab, an anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, in T1aN0M0 clear-cell RCC patients ineligible for surgical treatment.

Surgery remains the standard curative-intent therapy for localized renal cell carcinoma (RCC). Thus, systemic therapy for RCC should still be considered only in patients who have contraindications to surgery.

Results of Phase 3 CheckMate 214 study showed that a combination of nivolumab and ipilimumab has a significant impact on tumor burden in intermediate- and poor-risk metastatic RCC patients with a complete response rate of 11% (Motzer et al. Lancet Oncology 2019). Median time to objective response was 2.8 months. Among all complete responders to nivolumab plus ipilimumab in the intention-to-treat population, 5% achieved a complete response at the first scan, whereas most converted from the partial response at a median of 6.9 months or from the stable disease at a median of 11.3 months.

We hypothesize that this combination could completely eliminate primary tumors in patients with small primary (less than 4 cm) ineligible for surgical treatment. There are no studies evaluating checkpoint inhibitors in this setting in RCC patients.

Inclusion Criteria:

1. Cytologically proven clear-cell RCC
2. CT-confirmed measurable primary tumor less than 4 cm and no evidence of extranodal metastatic disease (T1aN0M0)
3. Inability to perform surgery for any reason (functional single kidney with a central, high-complexity RCC, high risk of nephrectomy and dialysis, patients with complex coagulation disorders, etc.) or preference of patient is to have no surgery for any reason
4. No contradictions to nivolumab and ipilimumab
5. Age 18 or older
6. Written informed consent

Exclusion Criteria:

1. prior treatment for RCC
2. pregnant or nursing
3. history of serious hypertension, cardiac arrhythmia, congestive heart failure, angina pectoris, or another severe cardiovascular disease (i.e., New York Heart Association class III or IV)
4. evidence of metastatic disease
5. local and/or systemic infections requiring antibiotics within 28 days prior to study entry
6. other malignancy