STING Agonist and Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy in Combination With Checkpoint Inhibition for Patients With Metastatic Kidney Cancer.
Summary
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).
Detailed description
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.
Arms & interventions
- DrugIMSA101
All enrolled patients to undergo the following treatment: SOC treatment: Nivolumab 480mg monthly PULSAR: 36 Gy in 3 fractions, Q4weeks IMSA101: three intra-tumoral injections of one of the progressive lesions at 1200 mcg (C1D1, C2D1, C3D1)
Outcome measures
Primary
To evaluate the PFS rate associated with the therapeutic intervention. PFS is defined as the duration of time from initiation of PULSAR/IMSA101 to disease progression as defined by RECIST1.1 or death.
Exact binomial test will be used to test if the lower limit of the 95% confidence interval of the probability of postponing systemic therapy \>9 months will be greater than 30%.
Time frame: Time from initiation of PULSAR/IMSA101 until death from any cause. Follow-up visits to be done every 12 weeks (+/- 1 week) for study duration until patient has progressed. Afterward, subjects to be contacted every 6 months for survival data up to 5 years
Eligibility criteria
Study locations (1)
University of Texas Southwestern Medical Center
Dallas, Texas, 75390