Radiotherapy + Checkpoint Inhibitor for Kidney Cancer

(SPARK Trial)

Overseen By RAQUIBUL HANNAN, MD, PhD.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Ultracentral chest lesions

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 17

Duration: 12 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for advanced kidney cancer that has spread. It combines a targeted radiation therapy called PULSAR with an injectable treatment, IMSA101 (a checkpoint inhibitor), and an immune therapy called nivolumab. The goal is to determine how effectively this combination stops cancer growth. People with kidney cancer that has spread to a few treatable areas may qualify, but those with lung metastases are not eligible. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that IMSA101 is likely a safe treatment. In earlier studies, patients used IMSA101 alone or with other treatments and found it generally safe, even at higher doses of 1,200 micrograms. Most patients did not experience serious side effects.

For the radiotherapy part, studies indicate that stereotactic ablative radiotherapy (SAbR) is effective and safe for kidney cancer. It did not damage kidney function in patients, suggesting it is well-tolerated.

Together, these treatments have demonstrated good safety records in previous research, providing some confidence about their use in trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for kidney cancer, which typically include surgery, targeted therapies, or immunotherapies like Nivolumab alone, the study treatment combines radiotherapy with a checkpoint inhibitor and a unique STING agonist, IMSA101. Researchers are excited because IMSA101 is administered directly into the tumor, which could enhance the immune system's response more effectively by activating local immune pathways. This approach aims to not just inhibit cancer growth but also to stimulate a more robust immune attack on the tumor, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

Research has shown that IMSA101, a drug that activates the immune system, may effectively fight tumors. Lab studies have demonstrated that it can strengthen the body's defense against cancer, especially when combined with other treatments. Meanwhile, stereotactic body radiotherapy (SAbR), a precise radiation therapy, has achieved a high success rate of 97.2% in treating kidney cancer in past studies. In this trial, researchers are combining IMSA101 with SAbR and another drug, nivolumab, to enhance treatment effectiveness. Early signs suggest that this combination might improve cancer control by directly killing cancer cells with radiation and boosting the immune system. ^{1 3 4 5 6}

Who Is on the Research Team?

RAQUIBUL HANNAN, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic renal cell carcinoma, a type of kidney cancer that has spread to other parts of the body. Specific eligibility criteria are not provided, so it's important to contact the study organizers for detailed requirements.

Inclusion Criteria

My cancer has spread to 3 or fewer places.

My organ and bone marrow functions are within normal ranges.

All IMDC risk categories are allowed

Exclusion Criteria

My cancer has not spread to the center of my chest.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PULSAR radiotherapy and IMSA101 injections in combination with Nivolumab

12 weeks

5 visits for IMSA101 injections, monthly visits for Nivolumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Follow-up visits every 12 weeks

Long-term follow-up

Participants are contacted every 3 months for survival data

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• IMSA101
• Radiotherapy

Trial Overview The trial is testing the effectiveness of PULSAR radiotherapy when combined with an injectable treatment called IMSA101 in slowing down or stopping the progression of metastatic kidney cancer.

How Is the Trial Designed?

Group I: SAbR with Intratumoral STING agonist IMSA101 and IO with Anti-PD1 Experimental Treatment 1 Intervention

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: three intra-tumoral injections of one of the progressive lesions at 1200 mcg (C1D1, C2D1, C3D1)

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

A 56-year-old woman with recurrent renal cell carcinoma showed significant reduction in multiple metastases after receiving conventional palliative radiotherapy following 22 cycles of nivolumab, an immune checkpoint inhibitor.

This case suggests that combining radiotherapy with immune checkpoint inhibitors may produce systemic effects, potentially leading to an abscopal effect, where localized treatment impacts distant metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible abscopal effect after discontinuation of nivolumab in metastatic renal cell carcinoma. Nakajima, N., Kano, T., Oda, K., et al.[2022]

Lenvatinib plus pembrolizumab had the highest rates of severe treatment-related adverse events (grade ≥3 TRAEs) and treatment discontinuation among the combination therapies for advanced renal cell carcinoma.

Nivolumab plus ipilimumab had the lowest rates of severe TRAEs but was linked to more endocrine-related adverse events, highlighting the need to balance efficacy with safety in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of systemic immune-based combination therapies in the first-line treatment of patients with metastatic renal cell carcinoma: systematic review and network meta-analysis. Quhal, F., Mori, K., Remzi, M., et al.[2023]

The combination of ipilimumab and nivolumab has been approved as the first dual checkpoint inhibitor therapy for treatment-naïve patients with intermediate to poor risk metastatic renal cell carcinoma (mRCC), marking a significant advancement in immunotherapy for this cancer.

This review discusses the trials that led to the approval of this combination therapy and highlights ongoing research, indicating a strong focus on optimizing treatment for various patient populations and addressing remaining clinical questions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and Nivolumab as First-Line Treatment of Patients with Renal Cell Carcinoma: The Evidence to Date. Sheng, IY., Ornstein, MC.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12182170/

Phase 1 first-in-human dose-escalation study of IMSA101, a ... IMSA101 is a small molecule analog of cGAMP and a potent STING agonist. Preclinical studies demonstrate antitumor activity of IMSA101 alone and in combination ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06601296

Study Details | NCT06601296 | Radiotherapy in ... To evaluate progression of metastatic renal cell carcinoma from the initiation of PULSAR radiotherapy in combination with IMSA101 injectable onward.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-03899

STING Agonist (IMSA101) and Personalized Ultra- ... This phase II trial studies how well IMSA101 and personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) with nivolumab works in treating ...

4. mdpi.com mdpi.com/1422-0067/26/18/9008

STINGing Cancer: Development, Clinical Application, and ... This review summarizes a selection of STING agonists evaluated in clinical trials to date and discusses their effects on tumor-infiltration immune cells, ...

5. advanced.onlinelibrary.wiley.com advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202509890

Emerging cGAS‐STING Agonist‐Based Nanotherapeutics ... This review summarizes recent advances in cGAS-STING agonist-based nanotherapeutics for cancer combination therapy.

6. researchgate.net researchgate.net/publication/392822646_Phase_1_first-in-human_dose-escalation_study_of_IMSA101_a_novel_cyclic_di-nucleotide_STING_agonist_for_patients_with_advanced_solid_tumor_malignancies

Phase 1 first-in-human dose-escalation study of IMSA101, ... Results 40 patients (22 monotherapy, 18 combination therapy) received at least one dose of IMSA101. IMSA101 1,200 µg (monotherapy) and 2,400 µg ...