^
    4d
    MAHOGANY: Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer (clinicaltrials.gov)
    P2/3, N=82, Completed, MacroGenics | Active, not recruiting --> Completed
    Trial completion
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • HER-2 positive
    |
    PD-L1 IHC 22C3 pharmDx
    |
    Herceptin (trastuzumab) • 5-fluorouracil • capecitabine • oxaliplatin • Margenza (margetuximab-cmkb) • Zynyz (retifanlimab-dlwr) • tebotelimab (MGD013)
    10d
    First-in-human phase I study of EMB-02, a bispecific antibody targeting PD-1 and LAG-3 in patients with advanced solid tumors. (PubMed, Br J Cancer)
    EMB-02 demonstrated a favorable safety profile and early efficacy signals in multiple solid tumors, warranting further development. (NCT04618393).
    P1 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • LAG3 (Lymphocyte Activating 3)
    |
    PD-L1 expression
    |
    EMB-02
    11d
    A Study to Evaluate Whether Participants With Melanoma Prefer Subcutaneous vs Intravenous Administration of Nivolumab and Nivolumab + Relatlimab Fixed-dose Combinations (clinicaltrials.gov)
    P2, N=100, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: Aug 2025 --> Apr 2025
    Trial primary completion date
    |
    Opdivo (nivolumab) • Opdualag (nivolumab/relatlimab-rmbw) • Opdivo Qvantig (nivolumab and hyaluronidase-nvhy)
    17d
    N-PLANC: Cemiplimab and Fianlimab Before Surgery for the Treatment of Stage IB-IIIB Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=60, Not yet recruiting, Mayo Clinic
    New P2 trial • Checkpoint inhibition
    |
    Libtayo (cemiplimab-rwlc) • fianlimab (REGN3767)
    17d
    ARID1A and/or KDM6A Mutation and CXCL13 Expression (clinicaltrials.gov)
    P2, N=6, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 6
    Enrollment closed • Enrollment change
    |
    ARID1A (AT-rich interaction domain 1A)
    |
    ARID1A mutation
    |
    Opdivo (nivolumab) • relatlimab (BMS-986016)
    23d
    KEYFORM-008: A Study of Coformulated Favezelimab/Pembrolizumab (MK-4280A) Versus Physician's Choice Chemotherapy in PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma (MK-4280A-008) (clinicaltrials.gov)
    P2, N=200, Active, not recruiting, Merck Sharp & Dohme LLC | Phase classification: P3 --> P2 | N=360 --> 200
    Phase classification • Enrollment change
    |
    gemcitabine • favezelimab/pembrolizumab (MK-4280A)
    24d
    A single-center phase II clinical study to evaluate the efficacy and safety of IBI110 in combination with sintilimab in the treatment of advanced metastatic or unresectable acinar soft tissue sarcoma (stage IV). (ChiCTR2500097943)
    P=N/A, N=30, Completed, Beijing Cancer Hospital; Beijing Cancer Hospital
    New trial
    |
    Tyvyt (sintilimab) • IBI110
    30d
    CA209-6D9: Pilot Study of Nivolumab w/Ipilimumab or Relatlimab in Surgically Resectable Melanoma Brain Metastases (clinicaltrials.gov)
    P1, N=1, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed | N=16 --> 1 | Trial completion date: Jun 2025 --> Aug 2024
    Trial completion • Enrollment change • Trial completion date
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Opdualag (nivolumab/relatlimab-rmbw) • relatlimab (BMS-986016)
    30d
    Treatment of metastatic melanoma with anti-PD-1 and anti-LAG-3 in a kidney transplant recipient. (PubMed, Immunotherapy)
    In this case, report, we highlight the successful use of a lymphocyte activation gene 3 (LAG-3) inhibitor, relatlimab, in combination with nivolumab (a programmed cell death protein 1 [PD-1] inhibitor) for the treatment of metastatic melanoma in a kidney transplant recipient. LAG-3 expression was notably positive in the renal graft, but negative in the metastatic melanoma tumor tissue. Although the outcome resulted in rapid renal graft rejection, this underscores the need for further research into LAG-3's dual role in cancer therapy and allograft rejection in organ transplant recipients.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    LAG3 (Lymphocyte Activating 3)
    |
    Opdivo (nivolumab) • relatlimab (BMS-986016)
    1m
    XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) in Treating Melanoma Prior Immune Checkpoint Inhibitor Therapy (clinicaltrials.gov)
    P1, N=6, Terminated, University of California, San Francisco | Trial completion date: Dec 2025 --> Apr 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Apr 2024; Sponsor decision
    Trial completion date • Trial termination • Trial primary completion date • Checkpoint inhibition
    |
    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • LAG3 (Lymphocyte Activating 3)
    |
    bavunalimab (XmAb22841) • izuralimab (XmAb23104)
    1m
    89Zr-DFO-REGN3767 in PET Scans in People With Diffuse Large B Cell Lymphoma (DLBCL) (clinicaltrials.gov)
    P1, N=7, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> Mar 2025 | Trial primary completion date: Sep 2025 --> Mar 2025
    Trial completion • Trial completion date • Trial primary completion date • IO biomarker
    |
    fianlimab (REGN3767)
    1m
    Immunologic correlates in a CIC::DUX4 fusion-positive sarcoma responsive to dual immune checkpoint blockade. (PubMed, NPJ Precis Oncol)
    Here, we present the first case of a patient with CDS responding to dual ICB with nivolumab and relatlimab. This case provides the first evidence of dual PD-1/LAG-3 blockade inducing an immune response in CDS. The favorable response and tolerability observed in this patient highlight the potential of dual ICB as a therapeutic option in CDS that merits further investigation.
    Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3) • FOXP3 (Forkhead Box P3) • DUX4 (Double Homeobox 4)
    |
    PD-L1 expression
    |
    Opdivo (nivolumab) • relatlimab (BMS-986016)
    1m
    KEYFORM-007: A Study of Coformulated Favezelimab/Pembrolizumab (MK-4280A) Versus Standard of Care in Subjects With Previously Treated Metastatic PD-L1 Positive Colorectal Cancer (MK-4280A-007)-China Extension Study (clinicaltrials.gov)
    P3, N=94, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed
    Trial completion
    |
    Keytruda (pembrolizumab) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil) • favezelimab/pembrolizumab (MK-4280A)
    1m
    KEYFORM-007: A Study of Coformulated Favezelimab/Pembrolizumab (MK-4280A) Versus Standard of Care in Subjects With Previously Treated Metastatic PD-L1 Positive Colorectal Cancer (MK-4280A-007) (clinicaltrials.gov)
    P3, N=505, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed
    Trial completion
    |
    Keytruda (pembrolizumab) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil) • favezelimab/pembrolizumab (MK-4280A)
    1m
    RELATIVITY-020: An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors (clinicaltrials.gov)
    P1/2, N=1499, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed
    Trial completion
    |
    Opdivo (nivolumab) • Opdualag (nivolumab/relatlimab-rmbw) • relatlimab (BMS-986016)
    1m
    CA209-1451: Neoadjuvant Opdualag Versus Nivolumab for Resectable High-Risk Basal Cell Carcinoma (clinicaltrials.gov)
    P2, N=30, Not yet recruiting, University of California, San Diego | Trial completion date: Feb 2028 --> May 2028 | Initiation date: Jan 2025 --> May 2025 | Trial primary completion date: Feb 2028 --> May 2028
    Trial completion date • Trial initiation date • Trial primary completion date
    |
    Opdualag (nivolumab/relatlimab-rmbw) • relatlimab (BMS-986016)
    1m
    RELATIVITY-073: A Study of Relatlimab in Combination With Nivolumab in Participants With Advanced Liver Cancer Who Have Never Been Treated With Immuno-oncology Therapy After Prior Treatment With Tyrosine Kinase Inhibitors (clinicaltrials.gov)
    P2, N=266, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Apr 2025 --> Oct 2025
    Trial completion date
    |
    Opdivo (nivolumab) • relatlimab (BMS-986016)
    1m
    Using Pharmacokinetic and Pharmacodynamic Analysis to Optimize the Dosing Regimens of Fanastomig (EMB-02) in Patients With Advanced Solid Tumors. (PubMed, CPT Pharmacometrics Syst Pharmacol)
    Based on these findings, two dosing regimens have been selected for further clinical development. Trial Registration: ClinicalTrials.gov identifier: NCT04618393.
    PK/PD data • Journal
    |
    LAG3 (Lymphocyte Activating 3)
    |
    EMB-02
    2ms
    Study of INCA32459 a LAG-3 and PD-1 Bispecific Antibody in Participants With Select Advanced Malignancies (clinicaltrials.gov)
    P1, N=46, Active, not recruiting, Incyte Corporation | Trial completion date: Apr 2026 --> Aug 2026 | Trial primary completion date: Apr 2026 --> Aug 2026
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    INCA32459
    2ms
    TRIPL: Thoracic Radiotherapy and Inhibition of PD-1 and LAG-3 for Locally Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=76, Not yet recruiting, Albert Einstein College of Medicine
    New P2 trial
    |
    cisplatin • carboplatin • docetaxel • albumin-bound paclitaxel
    2ms
    RELATIVITY-127: A Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination (FDC) in Previously Untreated Metastatic or Unresectable Melanoma (clinicaltrials.gov)
    P3, N=570, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting | Trial completion date: Aug 2025 --> Nov 2027
    Enrollment closed • Trial completion date
    |
    Opdualag (nivolumab/relatlimab-rmbw)
    2ms
    CA209-906: Nivolumab +/- Relatlimab Prior to Chemoradiation With II/III Gastro/Esophageal Cancer (clinicaltrials.gov)
    P1, N=32, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Mar 2025 --> Mar 2027
    Trial completion date • Trial primary completion date
    |
    Opdivo (nivolumab) • carboplatin • paclitaxel • relatlimab (BMS-986016)
    2ms
    A Study of Lomvastomig (RO7121661) and Tobemstomig (RO7247669) Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus (clinicaltrials.gov)
    P2, N=206, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Jan 2025 | Trial primary completion date: Jun 2025 --> Jan 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    Opdivo (nivolumab) • lomvastomig (RG7769) • tobemstomig (RG6139)
    2ms
    A Study of AK129 in Patients With Advanced Malignant Tumors (clinicaltrials.gov)
    P1, N=182, Recruiting, Akeso | Phase classification: P1a/1b --> P1 | Trial completion date: Feb 2025 --> Jun 2026 | Trial primary completion date: Feb 2025 --> Feb 2026
    Phase classification • Trial completion date • Trial primary completion date
    2ms
    Study to Evaluate the Safety and Efficacy of a Combination of Favezelimab (MK-4280) and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003) (clinicaltrials.gov)
    P1/2, N=174, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 --> Jan 2026 | Trial primary completion date: Oct 2028 --> Jan 2026
    Trial completion date • Trial primary completion date
    |
    Keytruda (pembrolizumab) • favezelimab (MK-4280)
    2ms
    Effect of prior and first-line immunotherapy on baseline immune biomarkers and modulation of the tumor microenvironment in response to nivolumab and relatlimab combination therapy in patients with melanoma from RELATIVITY-020. (PubMed, J Immunother Cancer)
    Nivolumab and relatlimab combination therapy can modulate the tumor microenvironment in patients with both IO-refractory and IO-naïve melanoma. Further research is needed to identify patients who will most benefit from anti-LAG-3/PD-(L)1 agents, and to elucidate the mechanisms of action of, and resistance to, this combination therapy in patients with advanced melanoma.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8)
    |
    PD-L1 expression
    |
    Opdivo (nivolumab) • relatlimab (BMS-986016)
    2ms
    A Study to Learn About the Long-Term Health of Adult Participants From a Previous Study of a New Melanoma Treatment (clinicaltrials.gov)
    P2, N=98, Not yet recruiting, Regeneron Pharmaceuticals
    New P2 trial
    |
    Libtayo (cemiplimab-rwlc) • fianlimab (REGN3767)
    2ms
    Induction IBI110 and Sintilimab with Chemotherapy in LA HNSCC (clinicaltrials.gov)
    P1/2, N=27, Recruiting, Fudan University | Active, not recruiting --> Recruiting | Phase classification: P1 --> P1/2 | N=20 --> 27
    Enrollment open • Phase classification • Enrollment change • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    paclitaxel • Tyvyt (sintilimab) • IBI110
    2ms
    The Risk of Adrenal Insufficiency after Treatment with Relatlimab in Combination with Nivolumab is Higher than Expected. (PubMed, J Clin Endocrinol Metab)
    This study is the first cohort analysis of hypophysitis in patients treated with relatlimab-nivolumab compared to nivolumab monotherapy. Combination treatment with relatlimab-nivolumab confers a significantly higher risk of developing adrenal insufficiency, likely secondary to hypophysitis, compared to nivolumab alone.
    Journal
    |
    LAG3 (Lymphocyte Activating 3)
    |
    Opdivo (nivolumab) • relatlimab (BMS-986016)
    2ms
    A Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Participants With Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma (clinicaltrials.gov)
    P2, N=199, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: May 2025 --> Oct 2026
    Trial primary completion date • Checkpoint inhibition
    |
    Keytruda (pembrolizumab) • Inlyta (axitinib) • tiragolumab (RG6058) • tobemstomig (RG6139)
    2ms
    A Study of Tobemstomig + Nab-Paclitaxel Compared With Pembrolizumab + Nab-Paclitaxel in Participants With Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov)
    P2, N=83, Active, not recruiting, Hoffmann-La Roche | N=160 --> 83
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    Keytruda (pembrolizumab) • albumin-bound paclitaxel • tobemstomig (RG6139)
    2ms
    Safety Study of BMS-986016 With or Without Nivolumab in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=35, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Jul 2025 --> Jul 2024
    Trial completion • Trial completion date
    |
    Opdivo (nivolumab) • relatlimab (BMS-986016)
    2ms
    The tetravalent, bispecific properties of FS118, an anti-LAG-3/PD-L1 antibody, mediate LAG-3 shedding from CD4+ and CD8+ tumor-infiltrating lymphocytes. (PubMed, Anticancer Drugs)
    We also show that PD-L1, not PD-1, binding drives the LAG-3 reduction on TILs. We hypothesize that the LAG-3 bivalency in the fragment crystallizable region of FS118 allows LAG-3 clustering, which optimizes cleavage by ADAM10/ADAM17 and thus shedding.
    Journal • Tumor-infiltrating lymphocyte • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3) • CD4 (CD4 Molecule) • ADAM17 (ADAM Metallopeptidase Domain 17) • ADAM10 (ADAM Metallopeptidase Domain 10)
    |
    FS118
    2ms
    Immuno-Oncology Drugs Elotuzumab, Anti-LAG-3 and Anti-TIGIT (clinicaltrials.gov)
    P1/2, N=14, Terminated, Multiple Myeloma Research Consortium | Trial completion date: Dec 2024 --> Aug 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Aug 2024; Pharmaceutical support has been discontinued.
    Trial completion date • Trial termination • Trial primary completion date
    |
    dexamethasone • pomalidomide • Empliciti (elotuzumab) • relatlimab (BMS-986016) • renvistobart (BMS-986207)
    2ms
    RELATIVITY-106: A Study of Nivolumab and Relatlimab in Combination With Bevacizumab in Advanced Liver Cancer (clinicaltrials.gov)
    P1/2, N=162, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    Opdivo (nivolumab) • Avastin (bevacizumab) • relatlimab (BMS-986016)
    2ms
    BGB-900-102: Study of BGB-A425 and LBL-007 in Combination With Tislelizumab in Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=114, Completed, BeiGene | Active, not recruiting --> Completed
    Trial completion
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Tevimbra (tislelizumab-jsgr) • alcestobart (LBL-007) • surzebiclimab (BGB-A425)
    2ms
    Gemcitabine/Cisplatin Plus Cemiplimab With or Without Fianlimab in Localized Muscle-invasive Bladder Cancer (NeoSTOP-IT) (clinicaltrials.gov)
    P2, N=36, Not yet recruiting, Columbia University | Initiation date: Nov 2024 --> Jun 2025
    Trial initiation date
    |
    cisplatin • gemcitabine • Libtayo (cemiplimab-rwlc) • fianlimab (REGN3767)
    2ms
    A Study of Cemiplimab and Fianlimab in People With Clear Cell Renal Cell Carcinoma (clinicaltrials.gov)
    P2, N=10, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting | Trial completion date: Dec 2026 --> Feb 2028 | Trial primary completion date: Dec 2026 --> Feb 2028
    Enrollment open • Trial completion date • Trial primary completion date
    |
    Libtayo (cemiplimab-rwlc) • fianlimab (REGN3767)
    2ms
    A Study of AK129 With or Without AK117 in PD(L)1-refractory Classic Hodgkin Lymphoma (clinicaltrials.gov)
    P1/2, N=280, Recruiting, Akeso | Not yet recruiting --> Recruiting | Initiation date: Oct 2024 --> Jan 2025
    Enrollment open • Trial initiation date
    |
    ligufalimab (AK117)
    2ms
    GIANT: Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab (clinicaltrials.gov)
    P2, N=92, Not yet recruiting, Duke University
    New P2 trial
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    Opdivo (nivolumab) • relatlimab (BMS-986016)
    3ms
    Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial. (PubMed, J Hematol Oncol)
    LBL-007 plus toripalimab exhibited a manageable safety profile in patients with advanced solid tumors and demonstrated promising antitumor activity in NPC, especially in immunotherapy-naive patients. These findings warrant further validation in future studies.
    P1/2 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Loqtorzi (toripalimab-tpzi) • alcestobart (LBL-007)
    3ms
    TRICK-MCC: Triple Immune Checkpoint Inhibition for Advanced or Metastatic PD-(L)1 Refractory Merkel Cell Carcinoma (clinicaltrials.gov)
    P2, N=12, Active, not recruiting, University of Washington | N=20 --> 12 | Trial completion date: Dec 2029 --> Apr 2027 | Trial primary completion date: Dec 2029 --> Jan 2027 | Recruiting --> Active, not recruiting
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Checkpoint inhibition
    |
    Zynyz (retifanlimab-dlwr) • tuparstobart (INCAGN2385) • verzistobart (INCAGN2390)