fianlimab (REGN3767) / Regeneron, Sanofi - LARVOL DELTA

Fianlimab, a human lymphocyte activation gene-3 monoclonal antibody, in combination with cemiplimab: Tumor-specific expansion cohorts in advanced malignancies. (PubMed, Cancer) - P1 | "Fianlimab plus cemiplimab demonstrated modest clinical efficacy with an acceptable safety profile in patients with advanced malignancies across several tumor types mostly in treatment-naive patients. Further investigation is warranted."

First-in-human • Journal • Clear Cell Renal Cell Carcinoma • Dermatology • Endocrine Disorders • Fatigue • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Pruritus • Renal Disease • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • LAG3

A Study of Radiation Therapy and Cemiplimab With or Without Fianlimab In People With Bladder Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Memorial Sloan Kettering Cancer Center | N=44 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

PHASE 2 STUDY OF UBAMATAMAB ALONE OR IN COMBINATION WITH ADDITIONAL AGENTS IN PATIENTS WITH PLATINUM-RESISTANT OVARIAN CANCER: TRIAL IN PROGRESS (IGCS 2026) - P2 | "Combination arms include ubamatamab + standard doses of bevacizumab (Arm B), triple immunotherapy (ubamatamab + cemiplimab + fianlimab; Arm C), and ubamatamab + pegylated liposomal doxorubicin (Arm D). Patients will receive sarilumab prophylaxis to mitigate CRS risk...Primary completion is December 2028. With limited immunotherapy options in PROC, ubamatamab may offer a novel approach."

Clinical • Combination therapy • P2 data • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor

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

Fianlimab&Cemiplimab as TotalNeoadj The (TNT) ForMelanoma (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: University of California, Irvine | Initiation date: Jul 2026 ➔ Dec 2026

Trial initiation date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

CLeAR: Cemiplimab +/- Fianlimab Post Y90 Radioembolization in Patients With Hepatocellular Carcinoma (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Virginia Commonwealth University | N=20 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Hepatocellular Cancer • Oncology • Solid Tumor

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

Phase II study of cemiplimab ± fianlimab following SBRT for oligometastatic clear-cell RCC (LAG-BOOST). (ASCO 2026) - P2 | "The study is powered for H₀: 65% versus Hₐ: 85% 1-year PFS, with α = 0.05 and power = 0.8. ClinicalTrials.gov identifier: NCT07223541."

Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Renal Cell Carcinoma • LAG3

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

Long-Term Overall Survival (OS) with Fianlimab (Fian) plus Cemiplimab (Cemi) in Advanced Melanoma (aMel): Survival Follow-Up of a Phase 1 Study (ESMO 2026) - No abstract available

Clinical • Metastases • P1 data • Melanoma • Oncology • Solid Tumor

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

NACho: Cemiplimab With Fianlimab for Resectable Non-Metastatic Colon Cancer (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: John Strickler, M.D. | Trial completion date: Nov 2029 ➔ Jun 2029 | Initiation date: Jul 2026 ➔ Oct 2026 | Trial primary completion date: Aug 2028 ➔ Dec 2028

Trial completion date • Trial initiation date • Trial primary completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal 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 | Initiation date: Jul 2026 ➔ Oct 2026

Trial initiation date • Hepatocellular Cancer • 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 | Trial primary completion date: Apr 2026 ➔ Aug 2026

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

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

Enrollment open • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor

Fianlimab + Libtayo: Data from P3 trial (NCT05608291) for adjuvant melanoma in Q4 2026 (Regeneron Pharmaceuticals) - Q2 2026 Results

P3 data • Melanoma • Oncology

Cemiplimab and Fianlimab With Neoadjuvant Chemotherapy in Early-Stage High-Risk ERBB2-Negative Breast Cancer: The I-SPY2 Randomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "Both groups received weekly paclitaxel for 12 weeks, then doxorubicin and cyclophosphamide followed by surgery; concomitant with paclitaxel, the intervention group also received 4 doses of cemiplimab and fianlimab (PCF) every 3 weeks. These results warrant further definitive trials. ClinicalTrials.gov Identifier: NCT01042379."

Clinical • IO biomarker • Journal • Breast Cancer • Endocrine Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Nephrology • Oncology • Renal Disease • Solid Tumor • Triple Negative Breast Cancer • HER-2

Phase II Study of Cemiplimab ± Fianlimab Following SBRT for Oligometastatic Clear-Cell RCC (LAG-BOOST) (NCT07223541) (KCRS 2026) - P2 | "The trial is currently open and actively enrolling patients. Conclusions N/A Keywords Oligometastatic clear cell renal cell carcinoma (ccRCC), Stereotactic body radiation therapy (SBRT), Dual checkpoint blockade (PD-1/LAG-3), Cemiplimab and Fianlimab DOD CDMRP Funding no"

IO biomarker • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Renal Cell Carcinoma • LAG3

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

Enrollment open • Minimal residual disease • Trial initiation date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

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=160 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | N=950 ➔ 160

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

A Trial to See if the Combination of Fianlimab With Cemiplimab Works Better Than Pembrolizumab for Preventing or Delaying Melanoma From Coming Back After it Has Been Removed With Surgery (clinicaltrials.gov) - P3 | N=1564 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Trial primary completion date: May 2028 ➔ Jul 2026

Trial primary completion date • Melanoma • Oncology • Solid Tumor

Androgen Deprivation, With or Without pTVG-AR, and With or Without T-Cell Checkpoint Blockade, in Patients With Newly Diagnosed, High-Risk Prostate Cancer (clinicaltrials.gov) - P1/2 | N=57 | Active, not recruiting | Sponsor: University of Wisconsin, Madison | Recruiting ➔ Active, not recruiting

Checkpoint inhibition • Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

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=149 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | N=850 ➔ 149 | Trial completion date: Feb 2032 ➔ Sep 2027 | Trial primary completion date: Mar 2030 ➔ Sep 2027

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

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

Enrollment open • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor