Safety and Efficacy of AMG 592 in Subjects With Steroid Refractory Chronic Graft Versus Host Disease

Key Inclusion Criteria:

- Male or Female ≥ 18 years old at the time of signing the informed consent.

- Recipient of an allogeneic HSCT.

- Moderate to severe steroid-refractory cGVHD as defined by all following criteria:

- Diagnosed with cGVHD per the 2014 cGVHD NIH Consensus Criteria(Jagasia, 2015;
Appendix 8) within the past 2 years prior to screening.

- Steroid refractory cGVHD, defined as having persistent signs and symptoms of
cGVHD despite ≥ 4 weeks of prednisone (or equivalent) dosed at ≥ 0.25 mg/kg/day
(or ≥ 0.5 mg/kg every other day) within the 12 months prior to screening.

- Moderate to severe cGVHD (in accordance with 2014 cGVHD NIH Consensus Criteria
[Jagasia, 2015; Appendix 9]) at screening with involvement of at least one of the
following organs at the screening and baseline visits: skin, mouth, eyes,
gastrointestinal (GI) tract, liver, lungs, and joint and fascia.

- No more than 3 previous treatments for cGVHD, excluding topical agents.

- Stable dose of ≤ 1 mg/kg/day of systemic prednisone or equivalent for at least 2 weeks
prior to first dose of AMG 592.

- Stable dose of non-corticosteroid immunosuppressants for the 2 weeks prior to first
dose of AMG 592.

- Karnofsky performance status score ≥ 50%.

- Adequate bone marrow function indicated by ANC > 1.00 x 109/L and platelets > 50 x
109/L without growth factors or transfusions within the 4 weeks prior to starting AMG
592.

Key Exclusion Criteria:

- Concurrently receiving treatment with calcineurin-inhibitor plus sirolimus (either
agent alone is acceptable).

- Received ibrutinib or following therapies considered investigational for treatment of
cGVHD including imatinib, bortezomib, ruxolitnib, or entospletinib, within 4 wks prior
to starting AMG 592 or is currently receiving treatment in another investigational
drug or device study.

- Treatment with T-cell depleting, B-cell depleting or IL-2 signaling targeted
medication (eg, ATG, alemtuzumab, basiliximab, denileukin diftitox, IL-2, rituximab
within 12wks prior to starting AMG 592.

- Treatment with T regulatory cell expanding therapies (ie ECP, PUVA, UVB, adoptively
transferred T regulatory cells) within 4 wks prior to starting dose of AMG 592.

- Donor lymphocyte infusion within 12 wks prior to starting dose of AMG 592.

- Active morphologic relapse/progression of hematologic malignancy post transplantation.

- History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic
thrombocytopenic purpura.

- Active infection requiring treatment with IV antibiotics or hospitalized for treatment
of an active infection in 4 wks prior to starting dose of AMG 592.

- History of active tuberculosis.

- Hep B and Hep C

- HIV-positive.

- Phase 1b subject has a positive drug or alcohol urine test at screening visit.

- Phase 1b subject is unable to avoid alcohol or tobacco consumption for the duration of
the study.