fianlimab (REGN3767) / Regeneron, Sanofi - LARVOL DELTA

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

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

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

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 | "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

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

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

R3767-ONC-2011: Clinical Study of Fianlimab in Combination With Cemiplimab Versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma (clinicaltrials.gov) - P3 | N=1546 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2025 ➔ Mar 2026

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

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 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Nov 2029 ➔ Dec 2030 | Initiation date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Apr 2027 ➔ Jun 2028

IO biomarker • Trial completion date • Trial initiation date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

ENCEFALO (GEM2301) clinical trial: Encorafenib and binimetinib followed by cemiplimab and fianlimab in BRAF-mutant melanoma and symptomatic brain metastases (ESMO-IO 2025) - P2 | "If among the first 18 pts, ≥4 had icPD at 6m or sooner, the study will stop. Accrual started in May 2025 and five patients were included by Sep 2025.Editorial acknowledgement Mfar Clinical Research staff."

Clinical • IO biomarker • Melanoma • Oncology • Solid Tumor • BRAF

Capecitabine/Oxaliplatin Chemotherapy and Cemiplimab With or Without Fianlimab or REGN7075 in Locally Advanced Rectal Cancer (clinicaltrials.gov) - P2 | N=66 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

New P2 trial • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

Opdualag vs. Cemiplimab/Fianlimab in Relation to the Immunological Response in Tumor and Peripheral Blood in Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: John Kirkwood | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor

LAG-MAPS: Trial Assessing Fianlimab Plus Cemiplimab Plus Chemotherapy or Cemiplimab Plus Chemotherapy in Patients With Pleural Mesothelioma (clinicaltrials.gov) - P2 | N=126 | Not yet recruiting | Sponsor: Intergroupe Francophone de Cancerologie Thoracique

New P2 trial • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • 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=180 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Apr 2029 ➔ Nov 2029 | Trial primary completion date: Sep 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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

New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

NACho: Cemiplimab With Fianlimab for Resectable Non-Metastatic Colon Cancer (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: John Strickler, M.D.

New P2 trial • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Opdualag vs. Cemiplimab/Fianlimab in Relation to the Immunological Response in Tumor and Peripheral Blood in Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P=N/A | N=20 | Not yet recruiting | Sponsor: John Kirkwood

New trial • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor

Fianlimab + Libtayo: Initial data from P2 trial (NCT06161441) for 1L advanced NSCLC in H1 2026 (Regeneron Pharmaceuticals) - Q3 2025 Results: Data from P3 trial (NCT05352672) for 1L metastatic melanoma in H1 2026

P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology

Fianlimab + Libtayo: Initiation of P2 trial (NCT06769698) for HPV+/HPV- HNSCC in H1 2026 (Regeneron Pharmaceuticals) - Q3 2025 Results: Initiation of trial for perioperative HNSCC in 2026

New trial • Trial initiation date • Oncology • Squamous Cell Carcinoma of Head and Neck