Trial: Cemiplimab or Cemiplimab and Fianlimab …

Trial Details

Sponsor: University of Oklahoma (other)

Phase: 2

Start date: Jan. 15, 2026

Planned enrollment: 72

Trial ID: NCT07223541

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: fianlimab (REGN3767)

Overview

Fianlimab (REGN3767) is an investigational, fully human monoclonal antibody targeting LAG-3 being developed primarily in combination with the PD‑1 inhibitor cemiplimab for melanoma and other solid tumors. Multiple phase 3 trials are ongoing in advanced and adjuvant melanoma and in first-line non–small cell lung cancer (NSCLC); no phase 3 efficacy results have been reported as of October 7, 2025. (ascopubs.org)

Mechanism of action

Target: Lymphocyte activation gene-3 (LAG‑3), an immune checkpoint receptor expressed on activated T cells. Fianlimab binds LAG‑3 to relieve inhibitory signaling; when combined with PD‑1 blockade (cemiplimab), dual checkpoint inhibition aims to enhance antitumor T‑cell activity. (ascopubs.org)

Efficacy

Advanced melanoma (phase 1, multicohort; fianlimab 1600 mg Q3W + cemiplimab 350 mg Q3W) - PD‑1–naïve advanced disease: ORR 63% in two independent cohorts (n=40 each); combined across three cohorts without prior anti‑PD‑1 for advanced disease (n=98), ORR 61.2% with median PFS 13.3 months (95% CI, 7.5–NE). CR rates were 12–15% across PD‑1–naïve cohorts. (ascopubs.org) - Prior anti‑PD‑1 in the adjuvant setting (relapse after adjuvant therapy; n=13 within a cohort of n=18): ORR 61.5% and median PFS 12 months (95% CI, 1.4–NE). (ascopubs.org) - Prior anti‑PD‑1 for advanced disease (n=15): ORR 13.3% and median PFS 1.5 months (95% CI, 1.3–7.7). (ascopubs.org) - Post hoc/independent review updates: In a combined analysis of PD‑1–naïve cohorts (n=98) with longer follow‑up, ORR 57% by BICR (CR 25%, PR 33%) was reported, with activity observed irrespective of baseline LAG‑3 or PD‑L1 expression. (onclive.com)

Ongoing phase 3 melanoma trials (no results yet) - First‑line unresectable/metastatic melanoma: fianlimab + cemiplimab versus pembrolizumab; primary endpoint PFS; estimated sample size ~1,500+. (ascopubs.org) - Adjuvant high‑risk resected melanoma: fianlimab + cemiplimab versus pembrolizumab (double‑blind, three‑arm design). (ascopubs.org) - Additional phase 3 head‑to‑head versus relatlimab+nivolumab is enrolling. (yalemedicine.org)

NSCLC (ongoing; no results yet) - Two randomized phase 2/3 trials: (1) PD‑L1 ≥50% tumors—fianlimab + cemiplimab versus cemiplimab; (2) all‑comers with chemotherapy—fianlimab + cemiplimab + chemotherapy versus cemiplimab + chemotherapy. (ascopubs.org)

Safety

Across the melanoma phase 1 cohorts of fianlimab + cemiplimab: - Grade ≥3 treatment‑emergent AEs occurred in 44% of patients; grade ≥3 treatment‑related AEs in 22%. An increased incidence of adrenal insufficiency was noted (any‑grade 12%, grade 3–4 4%) relative to typical PD‑1 monotherapy experience; otherwise, the safety profile was broadly comparable to PD‑1 inhibitors. Common AEs included fatigue and rash. (ascopubs.org)

TrialFetch AI Analysis

Goal: The trial is evaluating whether adding the LAG-3 inhibitor fianlimab to the PD-1 inhibitor cemiplimab after definitive stereotactic body radiotherapy improves outcomes in patients with oligometastatic clear cell renal cell carcinoma. The main objective is to compare 1-year progression-free survival with post-SBRT cemiplimab alone versus cemiplimab plus fianlimab, while also characterizing the safety of dual checkpoint blockade in this setting.

Patients: The study is enrolling adults with pathologically confirmed clear cell renal cell carcinoma and oligometastatic disease, defined as 1 to 5 RECIST-measurable metastatic lesions, all of which must be amenable to SBRT along with the primary tumor if present. Eligible patients may have ECOG performance status 0-2, adequate organ and marrow function, and selected treated or small minimally symptomatic untreated brain metastases. Key exclusions include variant histology RCC, prior combination systemic therapy for metastatic RCC, recent checkpoint inhibitor or other immuno-oncology therapy within 12 months, active autoimmune disease requiring systemic immunosuppression, significant uncontrolled cardiovascular or infectious comorbidity, gastrointestinal-invading metastases, more than 2 liver metastases or obstructive jaundice from liver disease, active inflammatory bowel disease, and pregnancy or breastfeeding.

Design: This is a randomized phase II treatment trial. All eligible patients first receive standard-of-care SBRT to all known sites of disease, including the primary tumor if present, using 1 to 5 fractions over approximately 1 to 2 weeks. Within about 3 weeks after completion of SBRT, patients are randomized 1:1 to cemiplimab plus fianlimab or cemiplimab alone. Treatment continues every 3 weeks for up to 17 cycles, approximately 1 year, or until recurrence, unacceptable toxicity, or an intercurrent illness prevents further treatment.

Treatments: Both arms receive cemiplimab 350 mg IV every 3 weeks for up to 1 year. Cemiplimab is an anti-PD-1 monoclonal antibody that enhances antitumor T-cell activity by blocking PD-1 signaling; PD-1 blockade is an established immune checkpoint strategy across multiple solid tumors, including renal cell carcinoma as part of broader immunotherapy-based treatment paradigms. The experimental arm also receives fianlimab 1600 mg IV every 3 weeks for up to 1 year. Fianlimab is a fully human IgG4 monoclonal antibody targeting LAG-3, an inhibitory checkpoint receptor expressed on activated T cells; blockade of LAG-3 is intended to restore T-cell effector function and may complement PD-1 inhibition. The most mature clinical data for fianlimab are in combination with cemiplimab in advanced melanoma, where a phase 1 study in anti-PD-1–naïve advanced melanoma reported an objective response rate of approximately 61% and median progression-free survival of 13.3 months; activity was lower in patients previously treated with anti-PD-1 in the advanced-disease setting. The combination has generally shown a checkpoint inhibitor safety profile, with notable immune-related toxicities including adrenal insufficiency reported more frequently than expected with PD-1 monotherapy.

Outcomes: The primary endpoint is the proportion of patients progression-free at 1 year after SBRT and treatment with cemiplimab alone versus cemiplimab plus fianlimab. Secondary endpoints include treatment-related, treatment-emergent, immune-mediated, and serious adverse events assessed by CTCAE v5.0; objective response rate by RECIST v1.1 and RANO criteria for brain metastases; local disease control and time to local progression by iRECIST; distant progression-free survival; duration of response; overall survival; and overall disease control rate, including complete response, partial response, and stable disease.

Burden on patient: The estimated patient burden is moderate. All participants undergo SBRT to every known disease site before systemic therapy, requiring radiation planning and 1 to 5 treatment fractions over 1 to 2 weeks, followed by IV immunotherapy visits every 3 weeks for up to 17 cycles. Monitoring will include routine laboratory testing, toxicity assessments, and serial imaging for response and progression, with additional brain MRI follow-up for patients with brain metastases. There are no described mandatory on-treatment biopsies or intensive pharmacokinetic blood-draw schedules, so the main added burden beyond standard oncologic care is the frequency and duration of infusion visits and the need to complete comprehensive SBRT to all disease sites before randomization.

Last updated: May 2026

Eligibility

Show Criteria

Inclusion Criteria:

* Patient must be \>= 18 years of age.

* Patient must have a biopsy/pathologically (histologically or cytologically) proven diagnosis of clear cell renal cell carcinoma (ccRCC) prior to randomization.

* Patient must have at least 1 and not more than 5 metastatic lesions measurable by RECIST v1.1, with imaging obtained within 45 days prior to randomization.

* Patients with untreated brain metastasis measuring \<2cm in diameter (intracranial RANO-BM measurable disease required) and with minimal neurological symptoms. Patients with treated brain metastasis are eligible for the trial as long as they have had three or fewer brain metastasis without signs of progression of disease on post-treatment MRI of the brain as per RANO for Brain Metastases (RANO-BM) guidelines.

* Patient must have documentation from a radiation oncologist confirming that all sites (metastases and primary tumor, if present) are amenable to stereotactic body radiation therapy (SBRT).

* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.

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

* Patient must have the ability to understand and the willingness to sign a written informed consent document.

* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

* Patients must have adequate organ and bone marrow function per protocol.

* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study.

* For patients with history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. If no previous history, testing for HBV is not required for entry onto the study.

* For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. If no previous history, testing for HCV is not required for entry onto the study.

* Patients with prior radiation to sites but without evidence of progression will be allowed, however these RT-treated sites will not be treated on study. Patients who have had a prior nephrectomy can be included in the study, patients with prior metastasectomy are also eligible for the study.

Exclusion Criteria:

* Patients with untreated brain metastasis \>2cm, significant neurological deficits and unamenable to surgical resection.

* Patient with variant histology renal cell carcinoma.

* Patient with metastasis invading gastrointestinal tract (such as esophagus, stomach, intestines, colon, rectum).

* Patients with more than 2 liver metastatic lesions, or liver lesions resulting in obstructive jaundice.

* Patient who have received any prior combination systemic therapy for metastatic RCC (including immune checkpoint inhibitors, tyrosine kinase inhibitors or combinations)

* Patients who have received any check point inhibitor or immune therapies (i.e. Vaccine or other immune-oncology agent) within the last 12 months. Patients who have previously been treated for non-metastatic RCC with adjuvant pembrolizumab can be included if over 12 months since last dose and they have not had radiographic progression within 12 months from the last dose of pembrolizumab

* Patients with active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

* Patients with no more than 1 prior systemic therapy for metastatic disease.

* Patients with active tuberculosis per protocol.

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

* Patients requiring major surgery within 30 days prior to randomization.

* Patients with any serious (requiring hospital stay or long-term rehab) non-healing wound, ulcer, or bone fracture within 30 days prior to randomization.

* Patients with any arterial thrombotic (ST elevation myocardial infarction \[STEMI\], non-STEMI \[NSTEMI\], cerebrovascular accident \[CVA\], etc.) events within 180 days prior to randomization.

* Patients with moderate or severe hepatic impairment (child-Pugh B or C).

* Patients with untreated pulmonary embolism (PE) or deep-vein thrombosis (DVT) is not allowed.

* Patients with unstable cardiac arrhythmia within 180 days prior to randomization.

* Patients with history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to randomization.

* Patients with history of or active inflammatory bowel disease.

* Patients with history of connective tissue disease or other disease in which radiation therapy is contraindicated.

* 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.

* Patients with a history of myocarditis.

* Patients with troponin T (TnT) or troponin I (TnI) \> 2x institutional ULN at baseline per protocol.

* Patients with history or current evidence of significant (CTCAE grade ≥2) local or systemic infection (e.g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.

* Patients with active infection requiring therapy.

* Patients with ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.

* Patients with uncontrolled infection with HIV, HBV, or HCV infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection per protocol.

* Patients with known hypersensitivity to the active substances or to any of the excipients.

* Patients who received a live vaccine within 30 days of planned start of study medication per protocol.

* Women who are fertile following menarche until becoming postmenopausal or women of childbearing potential (WOCBP\*), unless permanently sterile must have a negative serum (beta-hCG) at screening per protocol.

* Pregnant or breastfeeding women.

Sites (1)

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University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

[email protected] / 405-271-4022

Status: Recruiting

A Randomized Phase II Trial of Cemiplimab or Cemiplimab and Fianlimab After Stereotactic Body Radiotherapy in Oligo-Metastatic Clear Cell Renal Cell Carcinoma