ALPN-101 in Steroid-resistant or Steroid-refractory Acute GVHD

Phase 1

Terminated

Brief Summary: The Balance study will assess the safety, tolerability, and efficacy of an investigational drug called ALPN-101 in adults with steroid-resistant or steroid-refractory acute graft versus host disease (aGVHD).

Detailed Description: AIS-A02 is a Phase 1b open-label study of ALPN-101 administered to adult subjects with steroid-resistant or steroid-refractory acute graft versus host disease (aGVHD).

It will be conducted at approximately 10 US sites. Up to 72 subjects will be enrolled in Part A (dose escalation) and up to 25 subjects will be enrolled in Part B (dose expansion).

In each Part, safety and efficacy assessments will be performed throughout the dosing and follow-up periods, and multiple PK and PD samples will be collected.

Recruitment & Eligibility

Inclusion Criteria

Age ≥ 18 years
Status post first allogeneic stem cell transplantation (allo-SCT) from any donor source using any conditioning regimen.
Grade Ⅱ-Ⅳ acute GVHD per Mount Sinai Acute GVHD international Consortium (MAGIC) criteria.
Corticosteroid resistant or refractory as defined as any of the following:
1. Progression of aGVHD within 5 days following initiation of treatment with ≥ 2 mg/kg/day of prednisone or equivalent;
2. Failure to improve within 7 days following initiation of treatment with ≥ 2 mg/kg/day of prednisone or equivalent; or
3. Incomplete response (failure to achieve Complete Response) after 28 days of immunosuppressive treatment including steroids (treatment with ≥ 2 mg/kg/day of prednisone or equivalent).
Must agree to use appropriate contraception.
Female subjects must not be pregnant or breastfeeding.

In addition, the following criteria must be met prior to dosing with ALPN-101 on Day 1:
Karnofsky performance score ≥ 40.
No evidence of an active, uncontrolled bacterial, viral, or fungal infection.

Exclusion Criteria

Current veno-occlusive disease, or current treatment with dialysis or mechanical ventilation associated with GVHD.
Prior donor lymphocyte infusion (DLI).
Receipt of any live vaccine within 4 weeks of ALPN-101 dosing.
Presence of any active malignant disease.
Corticosteroid therapy at doses > 1 mg/kg/day prednisone or equivalent for indications other than GVHD ≤ 7 days p ALPN-101 dosing.
Treatment with any of the following ≤ 2 weeks prior to ALPN-101 dosing: targeted inhibitors of the CD28/CD80/86 pathway (e.g. abatacept, belatacept), targeted inhibitors of the ICOS/ICOSL pathway
Initiation of treatment with salvage therapy < 2 days prior to ALPN-101 dosing. Concurrent salvage therapy that is intended to be continued must be at a stable dose for ≥ 2 days prior to ALPN-101 dosing.
Treatment for aGVHD with adoptive cell therapy, investigational agents, devices, or procedures ≤ 2 weeks or 5 half-lives-whichever is greater-prior to ALPN-101 dosing, unless approved by the medical monitor and sponsor; prior treatment with mesenchymal stem cells is permitted.
Known allergies, hypersensitivity, or intolerance to study drug, excipients, or similar compounds.
Any medical complications or conditions that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.

Arm && Interventions

Group	Intervention	Description
ALPN-101	ALPN-101	All subjects will receive a single dose of ALPN-101. In Part A, ascending dose levels of ALPN-101 will be evaluated. In Part B, a single dose level of ALPN-101-as identified in Part A-will be evaluated.

Primary Outcome Measures

Name	Time	Method
Adverse events	From study Day 1 (dosing of ALPN-101) until Day 29	The incidence, severity, and seriousness of AEs, including dose-limiting toxicities, assessed by CTCAE

Secondary Outcome Measures

Name	Time	Method
Malignancy relapse/progression (MR)	From study Day 1 (dosing of ALPN-101) until the date of relapse/progression of the primary malignancy, assessed up to 36 months
Non-relapse mortality (NRM)	From study Day 1 (dosing of ALPN-101) until progression or death due to any cause without prior progression, assessed up to 36 months
Objective Response Rate (ORR)	From study Day 1 (dosing of ALPN-101) until the date of best response, assessed up to 36 months	Assessed by MAGIC criteria
Duration of Response (DOR)	From the date of best response until disease progression, assessed up to 36 months
Failure-free survival (FFS)	From study Day 1 (dosing of ALPN-101) until relapse, initiation of new systemic therapy, or non-relapse mortality; assessed up to 36 months
Event-free survival (EFS)	From study Day 1 (dosing of ALPN-101) until disease (aGVHD)-related event or death due to any cause, assessed up to 36 months
Time to maximum observed concentration (tmax) of ALPN-101	From study Day 1 (dosing of ALPN-101) until Day 29
Overall survival (OS)	From study Day 1 (dosing of ALPN-101) until death due to any cause, assessed up to 36 months
Area under the concentration-time curve (AUC) of ALPN-101	From study Day 1 (dosing of ALPN-101) until Day 29
Maximum observed concentration (Cmax) of ALPN-101	From study Day 1 (dosing of ALPN-101) until Day 29

Locations (4): University of Kansas Hospital
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Kansas City, Kansas, United States
St. David's South Austin medical Center
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Austin, Texas, United States
University of Miami
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Miami, Florida, United States
Sarah Cannon Center for Blood Cancer
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Nashville, Tennessee, United States