Posoleucel (ALVR105, Formerly Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant

Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of ALVR105 (Viralym-M) Compared to Placebo for the Prevention of AdV, BKV, CMV, EBV, HHV-6, and JCV Infection and/or Disease, in High-Risk Patients After Allogeneic Hematopoietic Cell Transplant

This is a Phase 2 study to evaluate posoleucel (ALVR105, formerly Viralym-M); an allogeneic, off-the-shelf multi-virus specific T cell therapy that targets six viral pathogens: BK virus, cytomegalovirus, adenovirus, Epstein-Barr virus, human herpesvirus 6 and JC virus.

This is a Phase 2/3, multicenter, randomized, double-blind, placebo controlled trial comparing posoleucel to placebo for the prevention of infection or disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV in high-risk adult and pediatric patients after allogeneic HCT.

There are 2 parts to the study, an open label Phase 2 cohort described in this posting, and a randomized, placebo controlled Phase 3 cohort described in NCT05305040. In the Phase 2 part, 25 to 35 eligible allogeneic HCT recipients will be enrolled and will receive 7 doses of posoleucel over 12 weeks, followed by a 14 week follow-up period.

Key Inclusion Criteria

• ≥1 year of age at the day of screening visit.

• Either no evidence of viral infection or viremia, or asymptomatic, viral infection with 3 or fewer viruses of interest at time of screening

• Within 15 and 42 days of receiving a first allogeneic HCT and have demonstrated clinical engraftment

• Meet one or more of the following criteria at the time of randomization:

  • Related (sibling) donor with at least one mismatch at one of these HLA-gene loci: HLA-A, -B or -DR
  • Haploidentical donor
  • Unrelated donor with at least one mismatch at one of these HLA-gene loci: HLA-A, -B, -C, or -DR
  • Use of umbilical cord blood as stem cell source
  • Ex vivo graft manipulation resulting in T cell depletion
  • Lymphocyte Count <180/mm3 and/or cluster of differentiation 4 (CD4) Count <50/mm3

Key Exclusion Criteria:

• History of AdV, BKV, CMV, EBV, HHV-6, and/or JCV end-organ disease within 6 months prior to randomization
• Evidence of active Grade >2 acute GVHD
• Presence of non-minor uncontrolled or progressive bacterial, viral or fungal infections
• Known history or current (suspected) diagnosis of CRS requiring treatment associated with the administration of peptides, proteins, and/or antibodies
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose >0.5 mg/kg/day) within 24 hours prior to dosing
• Relapse of primary malignancy other than minimal residual disease

Note: Other protocol defined Inclusion/Exclusion criteria may apply.