Cemiplimab + Fianlimab for Kidney Cancer

Recruiting at 6 trial locations

Overseen By Abraham Hakimi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immune checkpoint inhibitors, Corticosteroids

Disqualifiers: Autoimmune disease, Uncontrolled infection, Recent malignancy, 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: 9 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether two drugs, cemiplimab (an immunotherapy drug) and fianlimab (an experimental treatment), can be safely and effectively administered before kidney cancer surgery to shrink the tumor without delaying the operation. The trial focuses on patients with high-risk, non-metastatic clear cell renal cell carcinoma, a type of kidney cancer that hasn't spread beyond the kidney and nearby lymph nodes. Ideal participants are those already scheduled for kidney removal surgery due to this specific condition. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study treatment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that cemiplimab and fianlimab are likely to be safe for humans?

Research has shown that cemiplimab and fianlimab have been studied together for safety. Earlier studies found no unexpected safety issues when these treatments were combined, with side effects similar to those seen in past research with these drugs. Another study found that this combination worked well for patients with advanced melanoma, suggesting it can be effective and generally well-tolerated.

Since this study is in Phase 2, the treatment has already been tested for basic safety in humans, but more information is needed to fully understand its safety. Participants should consider this when deciding whether to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cemiplimab and fianlimab for kidney cancer because these treatments work by harnessing the power of the immune system in a novel way. Unlike traditional therapies like surgery, targeted therapy, or chemotherapy, which directly attack cancer cells, cemiplimab and fianlimab are immune checkpoint inhibitors. They target and block proteins that prevent the immune system from attacking cancer cells, enabling a more robust immune response against the tumor. This approach has the potential to be more effective and offer longer-lasting results by empowering the body's natural defenses to fight the cancer.

What evidence suggests that cemiplimab and fianlimab might be an effective treatment for kidney cancer?

Research shows that cemiplimab, when combined with fianlimab, yields promising results for treating certain cancers. In this trial, all participants will receive this combination. In patients with advanced clear cell renal cell carcinoma (a type of kidney cancer) who have undergone multiple treatments, this combination has led to lasting improvements. Cemiplimab blocks a pathway that cancer cells use to evade the immune system, while fianlimab targets another checkpoint to enhance the body's ability to fight cancer. Previous studies in patients with advanced melanoma showed response rates between 56% and 63% with this combination. These early results suggest that cemiplimab and fianlimab together could effectively treat kidney cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Martin Voss, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with clear cell renal cell carcinoma, a type of kidney cancer. Participants should be candidates for nephrectomy (kidney removal surgery) and must not have conditions that could delay surgery or affect the safety and effectiveness of the immunotherapy drugs cemiplimab and fianlimab.

Inclusion Criteria

Patient must be able to provide informed consent, or a legal authorized representative (LAR) must be identified to provide consent in cases where the patient cannot

Signed and dated IRB-approved Informed Consent Form

I have had a biopsy confirming clear cell cancer before starting treatment.

Exclusion Criteria

Patients with Troponin TnT or troponin I TnI > 2x institutional ULN at baseline

I have previously received immunotherapy.

I haven't taken steroids or immunosuppressants in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab and fianlimab every 3 weeks for a total of 3 treatments

9 weeks

3 visits (in-person)

Surgery

Participants undergo nephrectomy following treatment with cemiplimab and fianlimab

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Fianlimab

Trial Overview The study tests if giving two immunotherapy drugs, cemiplimab and fianlimab, before kidney removal surgery is feasible without causing delays. It also examines their safety, effectiveness in shrinking tumors pre-surgery, and overall impact on treatment outcomes.

How Is the Trial Designed?

Group I: Cemiplimab and Fianlimab Experimental Treatment 2 Interventions

All patients will be treated as follows: cemiplimab and fianlimab every 3 weeks for a total of 3 treatments, or until unacceptable toxic effects, overt disease progression, or withdrawal from study.

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

This pilot study involving 20 patients with metastatic renal cell carcinoma (mRCC) explored the immune effects of tyrosine kinase inhibitor (TKI) therapy, identifying specific T cell populations and soluble immune molecules that correlate with patient responses to treatment.

The findings suggest that profiling immune responses can help develop predictive biomarkers, potentially guiding better treatment strategies and improving outcomes for mRCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploratory Pilot Study of Circulating Biomarkers in Metastatic Renal Cell Carcinoma. Zizzari, IG., Napoletano, C., Di Filippo, A., et al.[2020]

Targeted therapies and immune checkpoint inhibitors, such as anti-PD-1 antibodies, have significantly improved response rates and survival outcomes for patients with renal cell carcinoma compared to traditional treatments like cytokines and chemotherapy.

Combination therapies, including treatments like axitinib with pembrolizumab and nivolumab with ipilimumab, have shown promising efficacy with response rates between 70-100%, although high toxicity and costs remain challenges in their widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy of Renal Cell Carcinoma]. Poprach, A., Lakomý, R., Büchler, T.[2019]

In a phase II trial involving 111 patients with metastatic renal cell carcinoma, the combination treatment of interleukin-2 (IL-2), interferon alfa-2a (IFNalpha), and fluorouracil (5-FU) showed a very low response rate of only 1.8%, indicating that this regimen is ineffective for this type of cancer.

The treatment was associated with moderate toxicity, including 3.6% of patients experiencing grade 4 adverse events and two treatment-related deaths, highlighting safety concerns with this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Français d'Immunothérapie. Ravaud, A., Audhuy, B., Gomez, F., et al.[2018]

The phase III IMmotion151 trial demonstrated that the combination of atezolizumab and bevacizumab significantly improves progression-free survival in patients with advanced or metastatic renal cell carcinoma compared to sunitinib.

Patients with PD-L1-positive tumors experienced an even greater benefit, with an increase in progression-free survival of 3.5 months, highlighting the efficacy of this combination therapy in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Combo Bests Sunitinib in RCC. [2019]

In a phase I trial involving 20 patients with metastatic renal cell carcinoma, the maximum tolerated dose (MTD) of 5-FU was determined to be 300 mg/m2, with significant toxicities including grade III nausea and one case of sudden cardiac death.

In the subsequent phase II trial with 25 patients, the combination therapy resulted in a 28% response rate, indicating some efficacy, but also increased toxicity, suggesting that further randomized trials are needed to evaluate the potential benefits of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and II trials of subcutaneously administered rIL-2, interferon alfa-2a, and fluorouracil in patients with metastatic renal carcinoma. Olencki, T., Peereboom, D., Wood, L., et al.[2019]

Sunitinib and pazopanib have been the standard first-line treatments for metastatic clear cell renal cell cancer (mccRCC) since their approval in 2007 and 2009, respectively, but recent advancements have introduced immunotherapy options that can be combined with tyrosine kinase inhibitors (TKIs).

New combinations of immunotherapy and TKIs, such as nivolumab/ipilimumab and various checkpoint inhibitors with TKIs, have been approved for treating mccRCC, although there is currently no specific biomarker to guide the selection of the most suitable treatment for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma. Popovic, M., Matovina-Brko, G., Jovic, M., et al.[2023]

In the IMmotion150 study involving 305 patients with metastatic renal cell carcinoma, atezolizumab combined with bevacizumab did not show a significant improvement in progression-free survival (PFS) compared to sunitinib, with a hazard ratio of 1.0, indicating similar effectiveness.

Exploratory analyses revealed that certain molecular profiles, such as angiogenesis and immune response signatures, may help predict treatment outcomes, suggesting that targeting VEGF could enhance the effectiveness of immunotherapy in overcoming resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. McDermott, DF., Huseni, MA., Atkins, MB., et al.[2022]

Combining VEGFR tyrosine kinase inhibitors with immune checkpoint blockers, like cabozantinib with nivolumab or axitinib with pembrolizumab, is now a standard treatment for advanced renal cell carcinoma, showing promising efficacy in clinical trials.

In silico drug modeling suggests that while these combinations are effective, the necessity of using both mechanisms may vary among patients, highlighting the potential for personalized treatment strategies based on tumor profiling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In silico modeling of combination systemic therapy for advanced renal cell carcinoma. Kotecha, RR., Hsu, DJ., Lee, CH., et al.[2023]

An ex vivo functional assay measuring the tumor cell killing ability of patient-derived cytotoxic lymphocytes (CLs) shows promise in predicting individual responses to PD-1/PD-L1 immune checkpoint inhibitors in renal cell carcinoma patients.

The newly developed PD-L1 inhibitor H1A was found to enhance CL activity more effectively than FDA-approved inhibitors like pembrolizumab and nivolumab, suggesting its potential as a next-generation treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel PD-L1 Antibody Promotes Antitumor Function of Peripheral Cytotoxic Lymphocytes after Radical Nephrectomy in Patients with Renal Cell Carcinoma. An, Z., Hsu, MA., Gicobi, JK., et al.[2023]

In the KEYNOTE-B61 trial involving 158 patients with advanced non-clear-cell renal cell carcinoma, the combination of pembrolizumab and lenvatinib demonstrated a 49% objective response rate, indicating significant antitumor activity as a first-line treatment.

The safety profile was consistent with previous studies, with 51% of patients experiencing grade 3-4 treatment-related adverse events, primarily hypertension, but no deaths were attributed to the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Albiges, L., Gurney, H., Atduev, V., et al.[2023]

Citations

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

Study Details | NCT07223541 | Cemiplimab or ... By binding to PD-1, cemiplimab (Libtayo) has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. Other ...

2. 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.

3. clin.larvol.com clin.larvol.com/trial-detail/NCT03005782

Study of REGN3767 (Anti-LAG-3) With or Without ... The presentations on fianlimab in combination with Libtayo will provide safety and efficacy data from three independent confirmatory cohorts of advanced ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07188896

A Randomized Trial of Fianlimab and Cemiplimab ... Karnofsky Performance Status ≥ 70% within 14 days prior to registration. Histological or cytological evidence of renal cell carcinoma having a ...

5. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/fianlimab-lag-3-inhibitor-combined-libtayor-cemiplimab-shows

Fianlimab (LAG-3 inhibitor) Combined with Libtayo® ... Data demonstrate objective response rates from 56% to 63% across three independent cohorts of advanced melanoma patients.

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

A phase 1 study of fianlimab (anti-LAG-3) in combination ... We present safety and clinical activity data from a Phase 1 study in patients with clear cell renal cell carcinoma (ccRCC) treated with anti–LAG ...

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

First-in-Human Dose-Escalation Study of Fianlimab, an ... There were no unexpected safety signals with fianlimab monotherapy or fianlimab-plus-cemiplimab combination therapy compared with previous reports for ...