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

Phase 2

Recruiting

• Conditions: Metastatic Renal Cell Carcinoma ( mRCC); OligoProgressive Metastatic Disease
• Interventions: Drug: IMSA101

• Registration Number: NCT06601296
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

To evaluate progression of metastatic renal cell carcinoma from the initiation of PULSAR radiotherapy in combination with IMSA101 injectable onward.

Detailed Description

The study expects to accrue the 20 patients over a 3-4 year period.

Patients with oligoprogressive disease (1-3 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 5 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.

Study Timeline

• Study First Submitted: 2024-09-11
• Study First Submitted QC: 2024-09-13
• Study First Posted: 2024-09-19
• Status Verified: 2025-04
• Study Start: 2025-04-01
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-04
• Primary Completion: 2027-10
• Study Completion: 2028-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Patients must have metastatic ccRCC.
• Patients must have oligoprogression defined as progression in ≤3 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. Lung metastases are excluded.
• ECOG performance status 0-2.
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SAbR with Intratumoral STING agonist IMSA101 and IO with Anti-PD1	IMSA101	Only one arm will be maintained in this phase II study with all patients undergoing the following treatment: SOC treatment: Nivolumab 480 mg monthly PULSAR: 36 Gy in 3 fractions, Q4weeks IMSA101: five intra-tumoral injections of one of the progressive lesions at 1200 mcg (C1D1, C1D8, C1D15, C2D1, C3D1)

Primary Outcome Measures

Name	Time	Method
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 3 months for survival data,up to 4 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 40%.

Trial Locations

Locations (1)

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States