Study to Evaluate the Safety and Pharmacokinetics of Efmarodocokin Alfa in Combination With Standard of Care in Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Genentech

Status and phase: Completed; Phase 1

Conditions: Acute Graft-versus-host Disease

Treatments: Drug: Efmarodocokin Alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT04539470

GA41825

Details and patient eligibility

About

This is a Phase Ib, open-label, multicenter, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics of Efmarodocokin Alfa and to make a preliminary assessment of activity of Efmarodocokin Alfa in combination with standard-of-care (SOC) in the prevention of acute graft-versus-host disease (aGVHD) in participants undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eligible for hematopoietic stem cell transplantation (HSCT)
• Donor meeting human leukocyte antigen (HLA) matching criteria of HLA-matched related or HLA-matched unrelated (HLA-A, HLA-B, HLA-C, and HLA-DRB1, eight out of eight) from either peripheral blood or bone marrow stem cells and meeting donor-eligibility criteria as outlined by the U.S. Food and Drug Administration (FDA) in 21 CFR 1271 (including screening for Zika and SARS-CoV-2 exposure or infection)
• Planned HLA (HLA-A, HLA-B, HLA-C, and HLA-DRB1)-matched (eight out of eight) related or planned HLA-matched (eight out of eight) unrelated HSCT, from either peripheral blood or bone marrow stem cells, for patients with acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) in first complete remission (per institutional criteria) or patients with intermediate or high-risk myelodysplastic syndrome (MDS)
• Planned myeloablative conditioning regimen per institutional guidelines
• Planned aGvHD prophylaxis consisting of tacrolimus and methotrexate; in cases of tacrolimus intolerance, cyclosporine or sirolimus may be used as a substitute

Exclusion criteria

• Prior receipt of autologous or allogeneic HSCT
• Diagnosis of myelofibrosis or myelodysplastic/myeloproliferative overlap syndrome
• Treatment with investigational biologic or non-biologic therapy within 5 drug elimination half-lives (or within 90 days or 30 days, respectively, if half-life is unknown) prior to initiation of study drug
• Positive hepatitis B virus (HBV) or hepatitis C virus (HCV) serologies
• History of Grade >1 cervical intraepithelial neoplasia
• A marked baseline prolongation of QT/QTc interval
• Risk factors for torsades de pointes
• Pregnant or breastfeeding
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

Cohort A: Efmarodocokin Alfa Dosage Level 1

Experimental group

Description:

Participants undergoing allogeneic hematopoietic stem cell transplantation will receive Efmarodocokin Alfa dosage level 1 in combination with standard of care prophylaxis treatment for acute graft versus-host disease (aGVHD), consisting of tacrolimus plus methotrexate per institutional practices.

Treatment:

Drug: Efmarodocokin Alfa

Cohort B: Efmarodocokin Alfa Dosage Level 2

Experimental group

Description:

Participants undergoing allogeneic hematopoietic stem cell transplantation will receive Efmarodocokin Alfa dosage level 2 in combination with standard of care prophylaxis treatment for acute graft versus-host disease (aGVHD), consisting of tacrolimus plus methotrexate per institutional practices.

Treatment:

Drug: Efmarodocokin Alfa

Cohort C: Efmarodocokin Alfa Dosage Level 3

Experimental group

Description:

Participants undergoing allogeneic hematopoietic stem cell transplantation will receive Efmarodocokin Alfa dosage level 3 in combination with standard of care prophylaxis treatment for acute graft versus-host disease (aGVHD), consisting of tacrolimus plus methotrexate per institutional practices.

Treatment:

Drug: Efmarodocokin Alfa