Cemiplimab + Fianlimab for Renal Cell Carcinoma

(LAG-BOOST Trial)

Overseen By Lead Nurse

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Oklahoma

Must not be taking: Corticosteroids, Immunosuppressives, others

Disqualifiers: Brain metastasis, Autoimmune disease, 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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of cemiplimab, used alone or with fianlimab, for individuals with clear cell renal cell carcinoma. The trial targets those who have undergone radiation therapy and have a few metastatic cancer spots. Suitable candidates have been diagnosed with this specific kidney cancer and have between one and five measurable cancer spots. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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. However, if you are on medications for active autoimmune disease or certain infections, you may need to discuss this with the trial team.

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

Research shows that the combination of cemiplimab and fianlimab is generally well-tolerated by patients with advanced clear cell kidney cancer. In studies, patients found this treatment manageable and experienced positive, long-lasting effects.

These drugs have undergone testing before, and the safety results were promising. Some patients experienced side effects, but they were usually mild. Cemiplimab aids the immune system in fighting cancer by blocking a protein called PD-1, while fianlimab targets a protein called LAG-3 in a similar manner.

Although side effects may occur, earlier research suggests these treatments are promising options. It is important to consult a healthcare provider before considering joining a trial to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for renal cell carcinoma, which often include drugs like sunitinib or pazopanib, Cemiplimab and Fianlimab offer a fresh approach by harnessing the power of the immune system. Cemiplimab is a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells more effectively. When combined with Fianlimab, an anti-LAG-3 antibody, this duo targets multiple immune checkpoints, potentially leading to a more robust and comprehensive immune response against the cancer. Researchers are excited because this combination could improve treatment outcomes by overcoming resistance mechanisms that limit the effectiveness of existing therapies.

What evidence suggests that this trial's treatments could be effective for renal cell carcinoma?

Research has shown that the combination of cemiplimab and fianlimab, which participants in this trial may receive, may effectively treat kidney cancer. Studies have found that this combination led to lasting improvements in patients with advanced clear cell kidney cancer who had already undergone many treatments. Specifically, about 61% of patients saw their cancer shrink. This treatment helps the body's immune system attack cancer cells more effectively. Using these two drugs together could potentially lead to better results for people with this type of cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Adanma Ayanambakkam, MD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for individuals with oligometastatic clear cell renal cell carcinoma who have finished radiation therapy. Specific inclusion and exclusion criteria are not provided, but typically these would involve factors like overall health status, prior treatments received, and the absence of conditions that could interfere with the study or pose additional risk to participants.

Inclusion Criteria

All patients of childbearing potential must have a serum test within 14 days prior to randomization to rule out pregnancy.

My cancer can be treated with targeted radiation according to my radiation oncologist.

My heart function is classified as class 2B or better, despite my history of cardiac issues or treatments.

Exclusion Criteria

Patients with uncontrolled hypertension (systolic blood pressure [BP] > 190mmHg or diastolic BP > 110mmHg).

Patient pregnant or breastfeeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.

Patients must not expect to conceive or father children and should use accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 6 months after the last dose of protocol treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants undergo standard of care SBRT to primary tumor and/or all metastatic tumor sites

1-2 weeks

1-5 fractions

Treatment

Participants receive cemiplimab with or without fianlimab every 3 weeks for up to 1 year

12 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Fianlimab

Trial Overview The trial is examining the safety and effects of a PD-1 inhibitor called cemiplimab alone or in combination with a LAG-3 inhibitor named fianlimab. These medications are given through an IV after patients have completed stereotactic body radiotherapy.

How Is the Trial Designed?

Group I: Cemiplimab + Fianlimab Experimental Treatment 2 Interventions

Cemiplimab, 350 mg, IV, and Fianlimab 1600 mg, IV, q3w for 1 year. Patients will undergo treatment with the study drug(s) every 3 weeks for a maximum of 17 cycles (approximately 12 months) or until disease recurrence, unacceptable toxic effects, or intercurrent illness preventing further administration.

Group II: Cemiplimab Active Control 1 Intervention

Cemiplimab 350 mg, IV, Q3W for 1 year. Patients will undergo treatment with the study drug(s) every 3 weeks for a maximum of 17 cycles (approximately 12 months) or until disease recurrence, unacceptable toxic effects, or intercurrent illness preventing further administration.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07223541

Study Details | NCT07223541 | Cemiplimab or ... The purpose of this research is to test the safety of PD-1 inhibitor cemiplimab with or without LAG-3 inhibitor fianlimab, and see what effects ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.434

A phase 1 study of fianlimab (anti-LAG-3) in combination ... Fianlimab + cemiplimab demonstrated promising signs of clinical activity with durable responses among patients with anti–PD-1/PD-L1-naïve (cohort 3) and anti– ...

3. onclive.com onclive.com/view/fianlimab-plus-cemiplimab-yields-early-efficacy-signs-in-pretreated-advanced-ccrcc

Fianlimab Plus Cemiplimab Yields Early Efficacy Signs in ... Fianlimab plus cemiplimab produced durable responses in heavily pretreated advanced clear cell renal cell carcinoma.

4. targetedonc.com targetedonc.com/view/fianlimab-plus-cemiplimab-shows-efficacy-in-pd-1-pretreated-metastatic-melanoma

Fianlimab Plus Cemiplimab Shows Efficacy in PD-1– ... The objective response rate (ORR) for fianlimab/cemiplimab was 61.2% in all patients, 60.9% in patients with any adjuvant treatment, and 61.5% ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-renal-cell-11-2024-45887

Cemiplimab + Fianlimab for Kidney Cancer Cemiplimab + Fianlimab is unique because it combines two immune checkpoint inhibitors, which may enhance the body's immune response against kidney cancer cells.

6. targetedonc.com targetedonc.com/view/positive-responses-are-reported-for-fianlimab-cemiplimab-in-ccrcc

Positive Responses Are Reported for Fianlimab ... Fianlimab plus cemiplimab was well-tolerated and showed durable responses, in pretreated patients with advanced clear cell renal carcinoma.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11647203/

First-in-Human Dose-Escalation Study of Fianlimab, an ... Conclusions: Fianlimab as monotherapy and in combination with cemiplimab demonstrated acceptable safety and preliminary antitumor activity, which is generally ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301624023939

Safety and Activity Profile of Fianlimab (Anti–LAG-3) in ... In the Phase 1b biomarker study, 33 pts were enrolled and treated with cemiplimab. 88% of pts were male and 46% were White. 70% of pts had prior ...