IL6-receptor Inhibitor Iwith Belumosudil for the Treatment of Belumosudil-refractory cGVHD

IL6-receptor Inhibitor in Combination With Belumosudil for the Treatment of Belumosudil-refractory Chronic Graft-versus-host Disease (cGVHD)

A single-center, Phase 1, open-label, investigator-initiated clinical trial evaluating the safety, tolerability, and preliminary efficacy of sarilumab (anti-IL-6R) monotherapy as a rescue in adult patients with belumosudil-refractory chronic graft-versus-host disease (cGVHD).

Study Overview

• Status: Not yet recruiting
• Conditions: cGVHD
• Intervention / Treatment: Drug: Belumosudil; Drug: Sarilumab

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sally Arai, MD; Phone Number: (650) 725-6186; Email: sarai1@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Active cGVHD and currently receiving belumosudil with inadequate response (defined as disease progression at any time or failure to achieve at least a partial response after a minimum of 3 months of belumosudil therapy, and for whom the treating physician believes a new systemic therapy is required).
3. Persistent cGVHD manifestations and systemic therapy indicated.

4. Karnofsky Performance Score of ≥ 60.

   Laboratory Parameters:

5. Absolute neutrophil count ≥ 1.5 x 109/L
6. Platelet count ≥ 50 x 109/L
7. ALT and AST < 1.5 × ULN
8. Total bilirubin ≤ 1.5 × ULN

9. Glomerular filtration rate (GFR) ≥ 30 ml/min/1.73m2

   General Criteria:

10. Negative urine pregnancy test at screening for females of childbearing potential.
11. Sexually active females of childbearing potential must agree to use two accepted methods of contraception during treatment and for 3 months after their last dose.
12. Sexually active male subjects with female partners of childbearing potential must agree to use two accepted methods of contraception and refrain from sperm donation during treatment and for at least 3 months after their last dose.

14. Ability to provide written informed consent (or consent from legally authorized representative). 15. Minimum weight of 63 kg

Exclusion Criteria:

1. Not on a stable systemic cGVHD treatments for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus are allowed. Systemic investigational GVHD treatments are not permitted).
2. Histological relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.

3. Current treatment with ibrutinib or ruxolitinib. Prior treatment is allowed with a washout of at least 1 week prior to randomization.

   General Criteria:

4. Pregnant or breastfeeding.
5. History or other evidence of severe illness or any other conditions that would make the subject, in the opinion of the sponsor-investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease or coronary artery disease).
6. Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) or history of human immunodeficiency virus (HIV).

7. Malignancy diagnosed within 3 years (other than malignancy for which transplant was performed), with the exception of:

   1. Completely resected basal cell or squamous cell carcinoma of the skin
   2. Carcinoma in situ of the cervix
   3. Resected breast ductal carcinoma in situ
   4. Prostate cancer with Gleason score <6 and stable PSA over 12 months
8. QTc(F) > 480 ms
9. Sponsor-investigator deems subject unlikely to adhere to study procedures/treatment.
10. Investigational agent, device, or procedure within 28 days of first dose (or 5 half-lives, whichever longer).
11. Active TB or a history of incompletely treated TB regardless of screening Quantiferon Result.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1: Sarilumab 150 mg + Belumosudil; Participants receive Belumosudil 200 mg orally once daily and sarilumab 150 mg subcutaneously every 2 weeks.	Drug: Belumosudil; Belumosudil (2-(3-(4-(1H-indazol-5-ylamino) quinazolin-2-yl) phenoxy)-N-isopropylacetamide-methane sulfonic acid salt), formerly also known as KD025, is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor. Belumosudil will be provided as 200 mg tablets.; Drug: Sarilumab; Sarilumab is an interleukin-6 (IL-6) receptor antagonist FDA approved for treatment of: Adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).; Adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. Sarilumab will be provided as single-use 1.14 ml prefilled glass syringes containing 131.6 mg/mL (150 mg), 175 mg/mL (200 mg) of sarilumab
Experimental: Dose Level 2: Sarilumab 200 mg + Belumosudil; Participants receive Belumosudil 200 mg orally once daily and sarilumab 200 mg subcutaneously every 2 weeks.	Drug: Belumosudil; Belumosudil (2-(3-(4-(1H-indazol-5-ylamino) quinazolin-2-yl) phenoxy)-N-isopropylacetamide-methane sulfonic acid salt), formerly also known as KD025, is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor. Belumosudil will be provided as 200 mg tablets.; Drug: Sarilumab; Sarilumab is an interleukin-6 (IL-6) receptor antagonist FDA approved for treatment of: Adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).; Adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. Sarilumab will be provided as single-use 1.14 ml prefilled glass syringes containing 131.6 mg/mL (150 mg), 175 mg/mL (200 mg) of sarilumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events	To evaluate the safety and tolerability of sarilumab monotherapy for the treatment of cGVHD after inadequate response to Belumosudil.	From first dose through 6 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Sarilumab	Maximum observed plasma concentration of sarilumab following administration.	Baseline through 6 months
Time to Maximum Plasma Concentration (Tmax) of Sarilumab	Time required to reach maximum plasma concentration following sarilumab administration.	Baseline through 6 months
Area Under the Plasma Concentration-Time Curve (AUC) of Sarilumab	Area under the plasma concentration-time curve used to characterize sarilumab exposure.	Baseline through 6 months
Incidence of serious infections	To evaluate the incidence of serious infections associated with sarilumab monotherapy as a rescue in subjects with belumosudil refractory cGVHD.	From first dose through 6 months
Overall response rate	To evaluate preliminary efficacy of sarilumab monotherapy as a rescue in subjects with cGVHD after inadequate response to belumosudil	Up to 6 months

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Sally Arai, MD, Stanford Universiy

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: sarilumab; belumosudil
• Other Study ID Numbers: IRB-83208

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes