Radiotherapy in Combination With Checkpoint Inhibition for Patients With Metastatic Kidney Cancer

STING Agonist and Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy in Combination With Checkpoint Inhibition for Patients With Metastatic Kidney Cancer.

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