Axatilimab in Combination With Extracorporeal Photopheresis (ECP) in Chronic Graft-versus-Host Disease

Inclusion Criteria:

1. Recipient of allogeneic hematopoietic cell transplantation (HCT).

2. Age greater or equal to 12.

3. Chronic GVHD per 2014 National Institutes of Health Consensus Criteria (NCC) (Jagasia et al. 2015) or overlap syndrome requiring new therapy in patients with atleast 2 prior lines of therapy, steroid refractoriness, or steroid dependence:

4. Prior systemic lines of therapy may include corticosteroids, calcineurininhibitor (CNI) or sirolimus, or other systemic immunosuppressive agent such asruxolitinib, belumosudil, or ibrutinib. GVHD prophylaxis does not count as aprior line of therapy.

5. Steroid refractory is defined as any of the following criteria:

• i. Manifestations progress despite the use of ≥ 1 mg/kg/day prednisone forat least 1 week
• ii. Manifestations persist without improvement despite treatment with ≥ 0.5 mg/kg/day or 1 mg/kg every other day for at least four weeks.
• iii. Recurrence after a CR, or
• iv. Progression after a PR.

3. Steroid dependence is defined as inability to control cGVHD symptoms whiletapering prednisone below 0.25 mg/kg/day on at least two occasions separated byat least 8 weeks. There must be evidence of clinically active cGVHD.

4. For patients receiving approved or commonly used agents, all GVHD systemictreatments should be discontinued except for corticosteroids and drugs beingcontinued from GVHD prophylaxis at screening.

5. Eastern Cooperative Oncology Group (ECOG) performance status 0-3 as assessed atScreening.

6. Platelet count > 50,000 platelets/μL and absolute neutrophil count > 1,000 cells/μLas measured at Screening.

7. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x upper limitof normal (ULN), unless attributed to presumed cGVHD as measured at Screening.

8. Stable dose of corticosteroids for at least 14 days prior to treatment.

9. Sexually mature individuals must use contraception as described in Section 4.12. Forindividuals less than 18 years of age, sexual maturity will be determined as pertreating pediatrician.

Exclusion Criteria:

1. Pregnancy or breast-feeding.

2. Active relapse of underlying malignancy.

3. History or the presence of interstitial pneumonitis or drug-related pneumonitis.

4. Active gastrointestinal (GI) bleeding.

5. Inability to tolerate volume shifts associated with ECP (e.g., inadequate renal,hepatic, pulmonary and cardiac function (ejection fraction (EF) < 40%) perInvestigator discretion.

6. History of myositis.

7. History of splenectomy.

8. History of pancreatitis.

9. History of other malignancy (within 3 years of Screening) unless treated withcurative intent and approved by Principal Investigator (PI).

10. Significant, uncontrolled, or active comorbid conditions or are unable to adhere tothe study requirements.

11. Acquired Immune Deficiency Syndrome (AIDS) or active hepatitis B (Hep B) or activehepatitis C (Hep C) infection.

12. Prior colony-stimulating factor-1 (CSF-1R) targeted therapies.

13. Prior history of ECP treatment failure or intolerance.

14. Intolerance to methoxsalen, heparin, or citrate products.

15. Patients with aphakia due to risk of increased retinal damage or photosensitivedisease (albinism, systemic lupus erythematosus, porphyria).

16. Lack of stable IV access. Acceptable forms include central venous catheter,peripherally inserted central catheter (PICC), or peripheral IV line perinstitutional guidelines.

17. Insurance denial of coverage for the ECP procedure.