Metastatic Renal Cell Carcinoma ( mRCC), OligoProgressive Metastatic Disease
Conditions
Keywords
renal, kidney, mrcc, metastatic, cancer, STING, PULSAR, SABr, SPARK, nivolumab, IMSA 101
Brief 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 (up to 5 lesions) after prior treatment with check-point inhibitor monotherapy (Nivolumab or Pembrolizumab). 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, 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.
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)
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have metastatic ccRCC. * Patients must have oligoprogressive disease (up to 5 progressing lesions) on any ongoing or prior check-point inhibitor regimen that are all amenable to radiation including one lesion suitable for IMSA101 injection. * Karnofsky Performance Status (KPS) of at least 50%. * Life expectancy of at least 6 months. * 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
* Prior high-grade toxicity from check-point inhibitors deemed to place he patient at high risk for toxicity recurrence with re-challenge with check-point inhibitors. * Prior STING agonist use. * Any condition requiring systemic treatment with corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. * Uncontrolled adrenal insufficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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 | 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%. |
Countries
United States
Contacts
CONTACTSARAH NEUFELD, MANAGER OF CLINICAL RESEARCH, MS, MBA
CONTACTRAQUIBUL HANNAN, MD, PhD.
PRINCIPAL_INVESTIGATORRAQUIBUL HANNAN, MD
University of Texas Southwestern Medical Center
Outcome results
None listed