Radiation and Immunotherapy for Liver Cancer

(PRISM Trial)

Overseen By Fabiana Gregucci, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must not be taking: High-dose steroids

Disqualifiers: Other malignancy, Autoimmune disease, HIV, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for liver cancer, which includes radiation and immunotherapy. Participants will receive targeted radiation on their tumors and two drugs, Tremelimumab and Durvalumab, to boost their immune system's ability to fight the cancer. The main goal is to determine the safety and effectiveness of this combination. Individuals with liver cancer that can be surgically removed and meet certain medical criteria may qualify for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the study team to understand any potential interactions or requirements.

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

Research has shown that the combination of Durvalumab and Tremelimumab is generally safe. In studies, patients tolerated this combination well, with some experiencing manageable side effects such as tiredness or mild skin reactions. This combination is already approved for some liver cancers, indicating its safety.

For the radiation therapy component, MRI-guided or CT-guided radiotherapy has been used safely to treat liver tumors. Studies indicate that patients tolerated this treatment well, with few serious side effects. Common mild effects included fatigue and skin changes at the treatment site.

Overall, previous research has found both treatments in this study to be generally well-tolerated, with the most common issues being mild and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Durvalumab and Tremelimumab for liver cancer because these treatments harness the power of the immune system in a new way. Unlike traditional therapies that directly target cancer cells, these medications are immune checkpoint inhibitors that help the body's own defenses recognize and fight the cancer more effectively. Durvalumab and Tremelimumab block specific proteins that often allow cancer cells to escape the immune response, potentially leading to better outcomes. This approach is particularly promising because it could offer a more targeted and potentially less toxic option compared to conventional chemotherapy or surgical methods.

What evidence suggests that this combination treatment could be effective for liver cancer?

This trial will evaluate the combination of Tremelimumab and Durvalumab with stereotactic body radiotherapy for liver cancer. Studies have shown that using Tremelimumab and Durvalumab together can extend survival in people with liver cancer. Specifically, the STRIDE treatment plan, which includes both drugs, resulted in better survival rates than Sorafenib for patients with liver cancer that cannot be surgically removed. This suggests that the combination might enhance the immune system's ability to fight cancer.

Research also shows that using MRI or CT scans to guide stereotactic body radiotherapy, a type of focused radiation treatment, is safe and effective for liver tumors. It has been successful in shrinking tumors while minimizing damage to healthy tissue. These findings make the combination of these treatments a promising option for patients with liver cancer in this trial. ^{1 4 5 6 7}

Who Is on the Research Team?

Encouse Golden, M.D.,PHD

Principal Investigator

Weill Cornell Medicine, New York, NY, USA

Are You a Good Fit for This Trial?

This trial is for individuals with resectable/advanced hepatocellular carcinoma, which is a type of liver cancer. Participants should be suitable for MRI or CT-guided radiotherapy and immunotherapy. Specific eligibility criteria are not provided but typically include factors like age, overall health, and the stage of cancer.

Inclusion Criteria

Patient must have measurable disease defined as a lesion that can be accurately measured in at least one dimension and measures ≥ 15 mm with conventional techniques or ≥ 10 mm with more sensitive techniques such as MRI or spiral CT scan.

I weigh more than 30kg.

My liver cancer is confirmed by a high-level scan or biopsy.

Exclusion Criteria

Patients must not be scheduled to receive another experimental drug while on this study.

Any underlying medical condition, which, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events.

Patients with prior orthotropic liver transplantation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Immunotherapy

Participants receive MRI-guided or CT-guided radiotherapy in three sessions (8 Gy each) and immunotherapy with a single dose of Tremelimumab and regular doses of Durvalumab every four weeks

7 weeks

3 radiation sessions, 1 Tremelimumab dose, 2 Durvalumab doses

Surgery

Participants undergo hepatic resection

1 week

1 surgical visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• MRI-guided or CT-guided Radiotherapy
• Tremelimumab

Trial Overview The study tests a new treatment combining radiation therapy (three sessions using MRI or CT guidance) with immunotherapy drugs Tremelimumab (one dose) and Durvalumab (every four weeks). The aim is to evaluate the safety and potential effectiveness of this regimen in treating liver cancer.

How Is the Trial Designed?

Group I: Stereotactic Body Radiotherapy for HCC Experimental Treatment 4 Interventions

Hypofractionated radiotherapy - 8Gy x3 fractions (week 0) Tremelimumab - single dose of 300 mg IV (week 0). Durvalumab - 1500 mg IV every 4-weeks (weeks 0-3) prior to hepatic resection Surgery - hepatic resection (week 7)

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Citations

1. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2100070

Tremelimumab plus Durvalumab in Unresectable ... The primary outcome was overall survival, defined as time from date of randomization until death from any cause, for STRIDE versus sorafenib.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40222621/

Five-year overall survival update from the HIMALAYA study ... STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) vs. sorafenib in unresectable HCC and demonstrated long- ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01462

Patient-Reported Outcomes From the Phase III HIMALAYA ... Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms.

4. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(24)02424-3/fulltext

Outcomes in the Asian subgroup of the phase III ... The global, phase III HIMALAYA study found that the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen improved overall survival ( ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2824%2900049-8/fulltext

Four-year overall survival update from the phase III ... Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39089633/

Outcomes in the Asian subgroup of the phase III ... In the Asian subgroup, ORR (including unconfirmed responses) was numerically higher for STRIDE (28.2%) and durvalumab (18.6%) vs. sorafenib (9.0 ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4122

Sequential or up-front triple combination with durvalumab ... The MONTBLANC trial evaluates the efficacy and safety of combined durva, treme and bev in patients (pts) with aHCC.