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

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).

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.

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥ 18 years
2. Status post first allogeneic stem cell transplantation (allo-SCT) from any donor source using any conditioning regimen.
3. Grade Ⅱ-Ⅳ acute GVHD per Mount Sinai Acute GVHD international Consortium (MAGIC) criteria.
4. 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).
5. Must agree to use appropriate contraception.
6. 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:
7. Karnofsky performance score ≥ 40.
8. No evidence of an active, uncontrolled bacterial, viral, or fungal infection.

Exclusion Criteria:

1. Current veno-occlusive disease, or current treatment with dialysis or mechanical ventilation associated with GVHD.
2. Prior donor lymphocyte infusion (DLI).
3. Receipt of any live vaccine within 4 weeks of ALPN-101 dosing.
4. Presence of any active malignant disease.
5. Corticosteroid therapy at doses \> 1 mg/kg/day prednisone or equivalent for indications other than GVHD ≤ 7 days p ALPN-101 dosing.
6. 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
7. 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.
8. 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.
9. Known allergies, hypersensitivity, or intolerance to study drug, excipients, or similar compounds.
10. 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.