Niktimvo (axatilimab-csfr) / Syndax Pharma, UCB, Incyte, Royalty - LARVOL DELTA

A phase Ib study of novel combination (New) of low dose oral cyclophoSphamide (S) To potentiate axatilimab (A) + retifanlimab (R) in treating metastatic Triple negative breast cancer (NEW START) (SABCS 2024) - No abstract available

Metastases • P1 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Axatilimab: First Approval. (PubMed, Drugs) - "Axatilimab was added to the NCCN guidelines for cGVHD in August 2024. This article summarizes the development milestones leading to this first approval of axatilimab for the treatment of cGVHD."

Journal • Review • Chronic Graft versus Host Disease • Graft versus Host Disease • Idiopathic Pulmonary Fibrosis • Immunology • Pediatrics • Pulmonary Disease • Respiratory Diseases • CSF1R

TRIAL IN PROGRESS: EVALUATING COMBINATION OF NIVOLUMAB AND AXATILIMAB IN PATIENTS WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA (NAHL) (ISHL 2024) - P2 | "Key secondary endpoints include frequency of AEs and serious adverse events (SAEs), PFS and ORR as measured by LYRIC criteria. Exploratory endpoints include: (i) pre-treatment and on-treatment lymph node biopsy to examine changes in tumor microenvironment, (ii) serial blood analysis including cytokine profile, circulating tumor DNA testing, and flow cytometry."

Clinical • IO biomarker • Endocrine Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • CSF1 • PD-L1

NAHL: Evaluating Combination of Nivolumab and Axatilimab in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=9 | Suspended | Sponsor: University of Utah | Recruiting ➔ Suspended

Trial suspension • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

Dynamics of Overall and Organ-Specific Responses to Axatilimab in Chronic Graft-Versus-Host Disease: Analysis from the Agave-201 Study (ASH 2024) - P2 | "Patients received a median of 4 prior therapy lines (range, 2–15), including ruxolitinib (74.3%), ibrutinib (31.1%), and belumosudil (23.2%). Most patients who achieved an overall clinical response or ≥7-point improvement in mLSS in the first 6 treatment cycles of AGAVE-201 did so by D84. By D56, more than half of responders had clinical responses and reported symptom improvement. Median times to organ-specific responses ranged from 1.0 to 3.7 months across organs; lower GI, upper GI, esophagus, liver, and joints/fascia were fastest to respond, whereas lung, mouth, eye, and skin responses were slower due to the highly fibrotic nature of these organ manifestations."

Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Inflammation • CSF1R

Axatilimab Abrogates Inflammatory Cytokines and Chemokines and Interrupts the Differentiation of Monocytes to Macrophages, a Pathogenic Driver of Inflammation and Fibrosis in Cghvd (ASH 2024) - P1/2, P2 | "Taken together, these data suggest that blocking CSF-1/CSF-1R signaling by axatilimab reduces proinflammatory signaling in monocytes and monocyte-derived macrophages and specifically reduces the number of monocytes and macrophages in the peripheral blood and peritoneal lavages of human CSF-1R knock-in mice. These data support the observation from clinical studies (phase 1/2 and pivotal AGAVE-201 study) that nonclassical monocytes were depleted in patients with cGVHD treated with axatilimab."

Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Inflammation • Oncology • CCL4 • CCL8 • CD14 • CXCL5 • CXCL6 • CXCL8 • ITGAM • PTPRC • TGFB1

Identification of High-Risk Patients and Establishment of a Clinical Prediction Model for Frontline Steroid Failure in Chronic Graft-Versus-Host-Disease (ASH 2024) - "Unrelated donor use, severe acute/chronic GvHD and ≥2 involved organs are high risk characteristics for frontline steroid failure. Future research should assess interventions including incorporation of newer agents such as ruxolitinib, belumosudil or axatilimab in addition to corticosteroids in these high-risk patients."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology

Exposure-Response Relationships for Axatilimab, a Humanized Monoclonal Antibody Targeting CSF-1R, in Patients with Chronic Graft-Versus-Host Disease (ASH 2024) - P1/2, P2 | "These results support the 0.3 mg/kg Q2W regimen of axatilimab in patients with cGVHD."

Clinical • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • CSF1R

Syndax Pharmaceuticals and Royalty Pharma Enter into $350 Million Royalty Funding Agreement for Niktimvo (PRNewswire) - "Under the terms of the agreement, Syndax received an upfront payment of $350 million in exchange for a 13.8% royalty on U.S. net sales of Niktimvo. Royalty payments to Royalty Pharma will cease upon reaching a multiple of 2.35x....Proceeds expected to support the upcoming planned launches and fund the continued development of Niktimvo and revumenib."

Financing • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease

Syndax to Host ASH Investor Event in Person and via Webcast on December 9, 2024 (PRNewswire) - "Syndax Pharmaceuticals...announced that the Company will host an in-person investor event, along with a live webcast, on Monday, December 9, 2024, at 7:00 a.m. PT/10:00 a.m. ET during the 66th American Society of Hematology (ASH) Annual Meeting in San Diego, California. Members of the Syndax management team will be joined by multiple key opinion leaders to discuss data updates from the Company's revumenib and Niktimvo (axatilimab-csfr) programs."

Clinical • Hematological Malignancies • Oncology • Solid Tumor

Syndax Announces New Data from Secondary Analysis of the Pivotal AGAVE-201 Trial of Niktimvo (axatilimab-csfr) in Chronic Graft-Versus-Host Disease to Be Presented at 66th ASH Annual Meeting (Syndax) - "Title: Dynamics of Overall and Organ-Specific Responses to Axatilimab in Chronic Graft-Versus-Host Disease: Analysis From the AGAVE-201 Study Presenter: Hannah Choe, M.D."

Syndax Announces New Data from Secondary Analysis of the Pivotal AGAVE-201 Trial of Niktimvo (axatilimab-csfr) in Chronic Graft-Versus-Host Disease to Be Presented at 66th ASH Annual Meeting (PRNewswire) - "Syndax Pharmaceuticals....today announced that multiple abstracts evaluating Niktimvo (axatilimab-csfr)...have been accepted for presentation at the 66th American Society of Hematology (ASH) Annual Meeting being held in San Diego, California, December 7-10, 2024. The presentations will highlight a secondary analysis of overall and organ-specific responses and findings from an exposure-response analysis in patients with chronic GVHD from the pivotal Phase 2 AGAVE-201 trial of Niktimvo, as well as preclinical data further characterizing the Niktimvo mechanism of action."

P2 data • Preclinical • Chronic Graft versus Host Disease

Axatilimab With or Without Azacitidine for the Treatment of Patients With Advanced Phase Myeloproliferative Neoplasms, Myeloproliferative Neoplasm/Myelodysplastic Syndrome Overlap or High Risk Chronic Myelomonocytic Leukemia (clinicaltrials.gov) - P1/2 | N=52 | Recruiting | Sponsor: Uma Borate | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Axatilimab in Combination With Extracorporeal Photopheresis (ECP) in Chronic Graft-versus-Host Disease (clinicaltrials.gov) - P2 | N=49 | Not yet recruiting | Sponsor: University of Miami

Combination therapy • New P2 trial • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

AGAVE-201 Study - FDA Approval of Axatilimab for Chronic Graft-versus-Host Disease (cGVHD) (YouTube) - "In this episode of the Oncology Brothers Podcast, host...welcome Dr. Shernan Holtan...to discuss the recent approval of Axatilimab, a novel monoclonal antibody for the treatment of chronic graft-versus-host disease (GVHD). Join us as we explore the differences between acute and chronic GVHD, the challenges faced by community oncologists in managing this condition, and the exciting results from the AGAVE-201 study that led to Axatilimab's FDA approval. Dr. Holtan shares insights on the drug's mechanism of action, its dosing regimen, and the importance of patient-reported outcomes in assessing treatment efficacy."

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Refractory encephalitis as an atypical manifestation of chronic graft-versus-host disease (DGHO 2024) - "A 25 year-old male patient received alloSCT for severe aplastic anemia after non-myeloablative conditioning including 2 Gy total body irradiation and GvHD prophylaxis with ATG, cyclosporine and MMF...Steroid taper during the following weeks resulted in progression of neurological symptoms but rotation to natalizumab induced complete remission of cGvHD...Re-initiation of fingolimod did not control the CNS disease and axatilimab (0.3mg/kg every 2 nd week) was started within a compassionate use program...Due to neurological deterioration, belumosudil was added however without any effect. This case instructively demonstrates core features of atypical CNS cGvHD I) initial diagnosis is frequently a diagnosis of exclusion with decent findings such as mild CNS fluid pleocytosis and response to immunosuppression; II) cMRI findings suggest that CNS GvHD follows the clinical course of classic cGvHD (inflammation, dysregulation and subsequent fibrosis); III) cGvHD can be highly..."

Anemia • Aplastic Anemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • CNS Disorders • Epilepsy • Fibrosis • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Rare Diseases • IL2

AGAVE-201: A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD) (clinicaltrials.gov) - P2 | N=241 | Active, not recruiting | Sponsor: Syndax Pharmaceuticals | Trial completion date: Dec 2024 ➔ Sep 2027

Trial completion date • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

OncLive’s August Roundup of Key FDA Approvals in Oncology (OncLive) - "Earlier this year, a panel of experts comprised of...Corey Cutler, MD, MPH...and Hannah Choe, MD...shared insights on emerging agents in GVHD as part of an OncLive Peer Exchange program. The panel reviewed the data shared during the 2023 ASH Annual Meeting and projected that axatilimab would be a promising addition to the chronic GVHD treatment arsenal, with unique mechanisms of action. However, they also acknowledged the need for careful consideration of its intravenous delivery and potential toxicities."

Evolving Landscape of Chronic GVHD Management: From Diagnosis to Novel Therapies : Episode 8: Clinical Considerations with Axtilimab in R/R GVHD (Targeted Oncology) - "Panelists discuss how clinical considerations shape the use of axatilimab in relapsed or refractory graft-versus-host disease, addressing factors that influence its application and management in practice."

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Controversy: Is Axatilimab becoming the new standard for chronic cGvHD? - No (COSTEM 2024) - No abstract available.

CSF-1R Inhibitor (Axatilimab) for Chronic GVHD (ICBMT 2024) - "Responses were not influenced by the extent of cGVHD involvement at baseline organ, number of received prior lines of treatment (including use of ruxolitinib, ibrutinib or belumosudil), and were seen across all organs, including sclerotic manifestation such as joints and fascia, esophagus, lung, and skin. Targeting CSF-1R–dependent monocytes and macrophages in refractory chronic GVHD with axatilimab represents a novel therapeutic strategy with high efficacy and manageable safety profile. Development of axatilimab in cGVHD continues, with studies planned in newly diagnosed and recurrent/refractory cGVHD, including corticosteroid-free approaches."

Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • CSF1R

Current Approaches for the Prevention and Treatment of Acute and Chronic GVHD. (PubMed, Cells) - "Calcineurin Inhibitors (CNI) with either Methotrexate (MTX) or Mycophenolate (MMF) still represent the standard prophylaxis in HLA-matched allogeneic stem cell transplantation (HSCT); other strategies focused on ATG, Post-Transplant Cyclophosphamide (PTCy), Abatacept and graft manipulation...For Ruxolitinib-refractory cGVHD, Belumosudil and Axatilimab represent the most promising agents. Bronchiolitis obliterans syndrome (BOS) still represents a challenge; among the compounds targeting non-immune effectors, Alvelestat, a Neutrophil elastase inhibitor, seems promising in BOS. Finally, in both aGVHD and cGVHD, the association of biological markers with specific disease manifestations could help refine risk stratification and the availability of reliable biomarkers for specific treatments."

Journal • Review • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation • ELANE

A Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

My Treatment Approach: Optimizing Treatment for Chronic GVHD : Episode 10: AGAVE-201: Axatilimab for cGVHD (OncLive) - "Medical experts discuss the mechanism of action within axatilimab."

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Evolving Landscape of Chronic GVHD Management: From Diagnosis to Novel Therapies : Episode 7: Axatilimab in Refractory/Recurrent cGVHD: A Promising Later-Line Option (Targeted Oncology) - "Panelists discuss how axatilimab emerges as a promising later-line treatment option for patients with refractory or recurrent chronic graft-versus-host disease (cGVHD), highlighting its potential in challenging cases."

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