To evaluate the impact of combining innate immune system activation (with IMSA101) with antigen release (through SAbR/PULSAR) on limited progressing lesions during ongoing adaptive immune system activation (with maintenance Nivo).

The study expects to accrue the 15 patients over a 3-4 year period.

Patients with oligoprogressive disease (≤5 lesions) after treatment with Anti-PD1 / Anti-CTLA-4 will continue Anti-PD1 (nivolumab). All patients will have a mandatory PD-L1 PET (Pre-treatment and Week 12). All patients will undergo baseline biopsy (just before the administration of IMSA101 of the same lesion to be injected). SAbR will be delivered in 3 fractions at 12 Gy every 4 weeks (PULSAR regimen) to all progressing lesions. One lesion will also receive 3 intratumoral injections of IMSA101 (C1D1, C1D8, C1D15, C2D1, C3D1) immediately after radiation either on the same day or within 72 hours after the PULSE.

Selected Phase 2 dosing of IMSA101 (1200mcg) will be utilized.

At disease progression, patients have the option to undergo additional imaging and tissue/blood collections.

Inclusion Criteria:

• Patients must have metastatic ccRCC.
• Patients must have oligoprogression defined as progression in ≤5 lesions.
• All oligoprogression lesions must be suitable for radiation.
• Patients must have at least one site of disease that can be safely injected with IMSA101.
• Karnofsky Performance Status (KPS) of at least 50%.
• Age ≥ 18 years.
• Patients must have adequate organ and marrow function within 14 days prior to study entry.
• All IMDC risk categories are allowed.

Exclusion Criteria:

• Patients with progressive ultracentral/central chest lesions will be excluded