fianlimab (REGN3767) / Regeneron, Sanofi - LARVOL DELTA

CLeAR: Cemiplimab +/- Fianlimab Post Y90 Radioembolization in Patients With Hepatocellular Carcinoma (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Virginia Commonwealth University | Initiation date: Feb 2026 ➔ Jul 2026

Trial initiation date • Hepatocellular Cancer • Oncology • Solid Tumor • CD4

Cemiplimab Plus Fianlimab for the Treatment of Locally Advanced Head and Neck Basal Cell Carcinoma Before Surgery (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Thomas Jefferson University | Trial completion date: Jul 2027 ➔ Jul 2031 | Trial primary completion date: Jul 2027 ➔ Jul 2031

Trial completion date • Trial primary completion date • Basal Cell Carcinoma • Head and Neck Cancer • Non-melanoma Skin Cancer • Oncology

A Study to See if Giving Fianlimab and Cemiplimab Together is Better Than Cemiplimab Alone at Treating Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

TRIPL: Thoracic Radiotherapy and Inhibition of PD-1 and LAG-3 for Locally Advanced Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - P2 | "Introduction : SPRINT (NCT03523702) was a multi-center Phase II trial where biomarker-selected (PD-L1 TPS ≥ 50%) locally advanced non-small cell lung cancer (LA-NSCLC) patients were treated with 3 cycles of induction therapy with the PD-1 inhibitor pembrolizumab followed by risk-adapted radiotherapy (RT), then consolidation pembrolizumab to complete a 1-year course while chemotherapy was omitted (PMID: 37988638)...Thus, we hypothesize that dual IO with the PD-1 inhibitor cemiplimab plus the LAG-3 inhibitor fianlimab administered before and after thoracic RT, as per the SPRINT approach, has valuable potential as a biomarker-driven treatment regimen for LA-NSCLC patients...Safety will be assessed via a safety-run in phase and extended adverse events collection. Additional endpoints will include ORR on CT, PFS, OS, quality of life assessments, and exploratory analyses focused on tissue and blood-based immune effector signatures."

IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LAG3

NSABP FC-13 (EMPIRE): A phase II platform study of cemiplimab monotherapy or cemiplimab-based combinations in patients with colorectal cancer and minimal residual disease (MRD) after definitive therapy. (ASCO-GI 2026) - P2 | " This multicenter Phase II platform study randomizes patients with MSS stage II–III or oligometastatic stage IV CRC who are ctDNA-positive within 12 weeks of completing definitive therapy (surgery ± chemotherapy/chemoradiotherapy) to one of three arms: 1) Cemiplimab 350 mg IV q3w × 1 year; 2) Cemiplimab 350 mg + fianlimab 1600 mg IV q3w × 1 year; and 3) Cemiplimab 350 mg + REGN7075 2700 mg IV q3w × 1 year. Statistical design: Arm 1 follows a Simon two-stage design with up to 33 patients (α=0.047, power=0.80), and Arms 2 & 3 enroll up to 23 patients each (single-stage; α=0.05, power=0.78). Status: Enrollment began in September 2025 across NSABP Foundation sites and is ongoing."

Clinical • IO biomarker • Minimal residual disease • Monotherapy • P2 data • Residual disease • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Cemiplimab With or Without Fianlimab to Treat Older Patients With Localized or Locally Advanced MSI-H Colorectal Cancer (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=33 ➔ 44

Enrollment change • MSI-H • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Non-animal platforms using ex-vivo human tissue and live-cell biosensors enable functional drug testing in renal cell carcinoma (AACR 2026) - "Treatment groups included: a) cabozantinib (cabo) alone, b) cabo with cemiplimab (cemi, a PD-1 inhibitor), c) cemi with fianlimab (fin, a LAG-3 inhibitor)...Cells were plated on biosensor-compatible microplates and treated with metabolic inhibitors (2-DG, oligomycin) and pharmacological targeted drugs relevant to RCC [(PI103- PI3K/mTOR inhibitor), sunitinib and cabozantinib (tyrosine kinase inhibitors), and linsitinib (IGF1R inhibitor)]... This integrated, fully non-animal strategy overcomes key limitations of animal models by combining preserved human tumor microenvironments with high-resolution metabolic biosensing. Together, these platforms enable rapid and mechanism-based profiling of therapeutic vulnerabilities in RCC."

Preclinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AMPK • HIF1A • LAG3

A Randomized Trial of Fianlimab and Cemiplimab +/- Ipilimumab or Ipilimumab Plus Nivolumab in First-line Advanced Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Brian Rini | Not yet recruiting ➔ Recruiting

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD4

A Study Comparing Two Immunotherapy Options for Human Papillomavirus Positive HPV-Positive Head and Neck Cancer After Treatment (clinicaltrials.gov) - P2 | N=68 | Not yet recruiting | Sponsor: University of Chicago | Initiation date: Jan 2026 ➔ Dec 2026

Minimal residual disease • Trial initiation date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

Trial assessing fianlimab plus cemiplimab plus chemotherapy or cemiplimab plus chemotherapy in patients with pleural mesothelioma (clinicaltrialsregister.eu) - P1/2 | N=126 | Not yet recruiting | Sponsor: Intergroupe Francophone De Cancerologie Thoracique

New P1/2 trial • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor

A phase 1/2 trial investigating REGN5668, a MUC16×CD28 costimulatory bispecific antibody, in combination with other targeted therapies in patients with recurrent ovarian or endometrial cancer: trial in progress update (ESGO 2026) - P1/2 | "In stage 1, 20 patients will be enrolled; if there are ≥3/20 objective responses, ≤50 patients will be enrolled in stage 2.Module 2 dose-escalation will evaluate REGN5668 + ubamatamab (± sarilumab [anti–interleukin-6 receptor α-subunit monoclonal antibody]) in an OC cohort using a Bayesian optimal interval design. Key secondary endpoints: ORR (Module 2 dose-escalation), safety and pharmacokinetics (Module 1 dose-expansion), further efficacy outcomes, immunogenicity.Results Module 1 dose-expansion has enrolled the first patient. Module 2 dose-escalation has progressed through multiple dose levels (enrolment ongoing).Conclusion This trial will evaluate REGN5668 + cemiplimab ± fianlimab or + ubamatamab in patients with OC/EC."

Clinical • Combination therapy • First-in-human • P1/2 data • Carcinosarcoma • Endometrial Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • IL6R • MUC16

LAG-BOOST: Cemiplimab or Cemiplimab and Fianlimab After Stereotactic Body Radiotherapy in Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P2 | N=72 | Recruiting | Sponsor: University of Oklahoma | Not yet recruiting ➔ Recruiting

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Significant durable response with fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) in advanced melanoma: Post adjuvant PD-1 analysis. (ASCO 2023) - P1, P3 | "2.0% of pts had received prior metastatic Tx (not anti–PD-(L)1) and 23.5% had received prior systemic Tx for Mel in the adj/neo-adj setting (disease-free interval > 6 mos), including 13.3% treated with an anti-PD-1 (nivolumab or pembrolizumab). Fianlimab + cemiplimab in advanced Mel pts showed high clinical activity that compares favorably with other approved combinations of immune checkpoint inhibitors in the same clinical setting. This is the first indication that dual LAG-3 blockade can produce high level of activity with significant ORR in pts with advanced Mel post adj anti-PD-1 Tx. The safety profile of fianlimab + cemiplimab is similar to anti-PD-1 monotherapy with the exception of AI."

Clinical • IO biomarker • Metastases • Endocrine Disorders • Immune Modulation • Melanoma • Nephrology • Oncology • Renal Disease • Solid Tumor

R3767-ONC-2208: A Trial to Learn if Fianlimab and Cemiplimab Are Safe and Work Better Than Anti-PD1 Alone in Adult Participants With Resectable Stage 3 or 4 Melanoma (clinicaltrials.gov) - P2 | N=151 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2031 ➔ Dec 2030 | Trial primary completion date: Mar 2027 ➔ Nov 2026

Enrollment closed • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

A Study of Radiation Therapy and Cemiplimab With or Without Fianlimab In People With Bladder Cancer (clinicaltrials.gov) - P2 | N=44 | Not yet recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Cemiplimab Plus Fianlimab for the Treatment of Locally Advanced Head and Neck Basal Cell Carcinoma Before Surgery (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Thomas Jefferson University | N=35 ➔ 70

Enrollment change • Basal Cell Carcinoma • Head and Neck Cancer • Non-melanoma Skin Cancer • Oncology

CLeAR: Cemiplimab +/- Fianlimab Post Y90 Radioembolization in Patients With Hepatocellular Carcinoma (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Virginia Commonwealth University

New P1 trial • Hepatocellular Cancer • Oncology • Solid Tumor • CD4

HARMONY LUNG-2: A Trial to Learn How the Combination of Fianlimab With Cemiplimab and Chemotherapy Works Compared With Cemiplimab and Chemotherapy for Treating Adult Patients With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P2/3 | N=950 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Biomarker • Enrollment closed • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

HARMONY LUNG-1: A Study to Learn if a Combination of Fianlimab and Cemiplimab Versus Cemiplimab Alone is More Effective for Adult Participants With Advanced Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=850 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A Trial of Locoregionally Advanced Squamous Cell Carcinoma of The Head and Neck (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: University of Chicago

New P2 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Evaluation of anti-PD-1 Cemiplimab plus anti-LAG-3 REGN3767 in early-stage, high-risk HER2-negative breast cancer: Results from the neoadjuvant I-SPY 2 TRIAL (SABCS 2022) - "Treatment included Paclitaxel 80 mg/m2 IV weekly x 12 and Cemiplimab 350 mg and REGN3767 1600 mg both given q3weeks x 4, followed by doxorubicin/cyclophosphamide (AC) every 2 weeks x 4. The I-SPY 2 study aims to assess the probability that investigational regimens will be successful in a phase 3 neoadjuvant trial. Dual immune blockade with a LAG-3 inhibitor and anti-PD1 therapy resulted in a high predicted pCR rate both in HR-/HER2- (60%) and HR+/HER2- (37%) disease. The novel Imprint signature identified a group of HR+ patients most likely to benefit from this active regimen."

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • LAG3

A phase 1 study of fianlimab (anti-LAG-3) in combination with cemiplimab (anti-PD-1) in patients with advanced melanoma: Poor-prognosis subgroup analysis. (ASCO 2023) - P1, P3 | "The combination of fianlimab and cemiplimab showed high activity in pts with advanced Mel and poor prognosis features at BL. The ORR and DCR observed in these subgroups compare positively with the available data for approved combinations of iCPIs in the same clinical setting. A phase 3 trial (NCT05352672) of fianlimab + cemiplimab in Tx-naïve advanced Mel pts is ongoing."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Immune Modulation • Melanoma • Oncology • Solid Tumor

A Trial to Learn if the Combination of Fianlimab, Cemiplimab, and Chemotherapy is Safe and Works Better Than the Combination of Cemiplimab and Chemotherapy in Adult Patients With Non-Small Cell Lung Cancer That Can be Treated With Surgery (clinicaltrials.gov) - P2 | N=195 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

...Eylea outlook and 2026 catalysts (Streetinsider.com) - "Ahmad pointed to a busy 2026 catalyst calendar, including the 'LAG3 readout in 1H26,' an expected Eylea HD PFS approval 'mid-2026,'..."

Approval • P3 data • Diabetic Macular Edema • Diabetic Retinopathy • Melanoma • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

A Randomized Trial of Fianlimab and Cemiplimab +/- Ipilimumab or Ipilimumab Plus Nivolumab in First-line Advanced Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Brian Rini | Initiation date: Nov 2025 ➔ Feb 2026

Trial initiation date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor