A Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease

A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease

This study will be conducted to determine the preliminary efficacy of axatilimab in combination with ruxolitinib and to assess the contribution of axatilimab to the combination treatment effect in participants with cGVHD.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Graft-versus-host-disease
• Intervention / Treatment: Drug: Axatilimab; Drug: Ruxolitinib; Drug: Corticosteroids

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Incyte Corporation Call Center (US); Phone Number: 1.855.463.3463; Email: medinfo@incyte.com
• Study Contact Backup: Name: Incyte Corporation Call Center (ex-US); Phone Number: +800 00027423; Email: eumedinfo@incyte.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ≥ 12 years of age at the time of informed consent.
• New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Development Project Criteria for Clinical Trials in cGVHD, requiring systemic therapy.
• History of 1 allo-SCT (any type of stem cell donor, any conditioning regimen, and source of hematopoietic stem cells).
• Adequate hematologic function independent of platelet transfusion and growth factors for at least 7 days prior to study entry: ANC ≥ 0.75 × 109/L and platelet count ≥ 20 × 109/L.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Received more than 1 prior allo-SCT. Prior autologous HCT is allowed.
• Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD.
• Received previous systemic treatment for cGVHD, including systemic corticosteroids and extracorporeal photopheresis.
• Received systemic corticosteroids within 2 weeks prior to C1D1, regardless of indication.
• Initiated systemic treatment with CNIs or mTOR inhibitors within 2 weeks prior to C1D1.
• Prior treatment with a JAK inhibitor within 8 weeks before randomization. Participants who received a JAK inhibitor for the treatment of aGVHD are eligible only if they achieved a response (CR or PR) to JAK inhibitor treatment and did not discontinue due to toxicity.
• Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-SCT was performed, including DLIs for the treatment of molecular relapse.
• History of acute or chronic pancreatitis.
• History of thromboembolic events (such as deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction) in the 6 months prior to study entry.
• Active symptomatic myositis.
• Severe renal impairment, that is, estimated CrCl < 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or end-stage renal disease on dialysis. Participants with CrCl of 30 to 59 mL/min on treatment with fluconazole are not eligible.
• Impaired liver function, defined as total bilirubin > 1.5 × ULN and/or ALT and AST > 3 × ULN in participants with no evidence of liver cGVHD.
• Currently active significant cardiac disease, such as uncontrolled arrhythmias, uncontrolled hypertension, or Class 3 or 4 congestive heart failure as defined by New York Heart Association, or a history of myocardial infarction or unstable angina within 6 months prior to randomization.
• Pregnant or breastfeeding.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group A; Axatilimab will be administered at a protocol defined starting dose plus ruxolitinib at a protocol defined starting dose.	Drug: Axatilimab; Axatilimab will be administered at protocol defined dose.; Drug: Ruxolitinib; Ruxolitinib will be administered at protocol defined dose.
Experimental: Treatment Group B; Ruxolitinib will be administered at a protocol defined starting dose.	Drug: Ruxolitinib; Ruxolitinib will be administered at protocol defined dose.
Experimental: Treatment Group C; Corticosteroids alone will be administered at a protocol defined starting dose.	Drug: Corticosteroids; Corticosteroids will be administered at protocol defined dose.; Other Names: prednisone, prednisolone, methylprednisolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Defined as Complete Response (CR) or Partial Response (PR) at 6 months in the absence of new systemic therapy for cGVHD. Response assessment will be based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with a ≥ 7-point improvement in modified Lee symptom scale (mLSS) score		Up to 2 years
Axatilimab pharmacokinetic (PK) in Plasma	Axatilimab concentration in plasma.	Up to 2 years and 30 days
Number of participants with Treatment-emergent Adverse Events (TEAEs)	Defined as adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment.	Up to 2 years and 30 days
Duration of Response	Defined as the time from the first response (PR or CR) to the date of progression of cGVHD, start of new systemic therapy or death from any cause.	Up to 2 years
Best overall response in the first 6 months	Define as PR or CR in the first 6 months.	Up to 6 months
OR at 12 months, defined as CR or PR at 12 months (C14D1) in the absence of new systemic therapy for cGVHD.	Defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD	12 months
Proportion of participants who remain corticosteroid-free		4 weeks, 8 weeks and 6 months
Organ-specific response in the first 6 cycles and on study, based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.	Based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.	Up to 2 years
Failure-free Survival (FFS)	Defined as the time from date of randomization to date of initiation of a new cGVHD treatment, malignancy relapse, or death due to any cause.	Up to 2 years and 30 days
Ruxolitinib PK in Plasma	Ruxolitinib concentration in plasma.	Up to 2 years and 30 days

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Incyte Medical Monitor, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): July 8, 2024
• Primary Completion (Estimated): March 5, 2027
• Study Completion (Estimated): September 5, 2028

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: cGVHD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone; Prednisone
• Other Study ID Numbers: INCA34176-254; 2022-502168-19-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No