Multi-Respiratory Virus T-Cell Therapy Well-Tolerated after HCT

Sarah Nikiforow, MD, PhD

Credit: Dana-Farber

ALVR106 (AlloVir) multi-respiratory virus T-cell therapy was safe and well tolerated in adult patients with upper or mild lower respiratory tract infections after receiving hematopoietic cell transplant (HCT) or solid organ transplant (SOT).¹

The data, from a phase 1/2 clinical trial (NCT04933968), were presented at the 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024, by Sarah Nikiforow, MD, PhD, Medical Director, Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute, and Assistant Professor of Medicine, Harvard Medical School.

“Upper respiratory infections in these viruses are one responsible for up to 40% in some of the infections in our HSCT patients. Upper respirator tract infections can lead to lower respiratory tract infections which have high mortality rates. Although were getting better at our vaccination strategies, we don’t have great therapies once people have active disease. So, this is where ALVR106 comes in,” Nikiforow said during her presentation.

ALVR106 is an allogeneic, off-the-shelf, polyclonal, multi-respiratory virus T-cell therapy specific for influenza (Flu), human metapneumovirus (hMPV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). The therapy is generated by exposing peripheral bone marrow cells to viral peptides with activating cytokines to create Th1-polarized and polyfunctional cells that selectively kill viral target cells. ALVR106 cells have not shown alloreactivity.

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“These are a polyclonal multi-virus specific lot, but in a given individual, say with RSV, it’s the RSV-directed CD4 and cd8 T-cells that will expand, hone to the site of infection. These are allogeneic, there is no expectation of there being long term engraftment here. These are to be used as a bridge to get through the acute infection, maybe until there’s an immune system change that will allow the body to protect itself against these viruses,” Nikiforow said.

The new data are from 16 patients treated in the trial who received 1×10⁵ (n = 3), 5x10⁵ (n = 4), 1x10⁶ (n = 4), 2×10⁶ cells/kg (n = 3), or placebo (n = 2). Participants received up to 2 infusions of ALVR106. One patient each in cohorts 2-4 had upper respiratory tract infection at baseline. No patients had Flu and only 1 patient, in cohort 2, had RSV. Most patients had hMPV. Nikiforow noted that only 1 patient included in the trial had received SOT while the rest received HCT.¹

There were no serious adverse events (AEs) grade 3 or higher considered related to the therapy, although there were some incidences of mild diarrhea and hyperglycemia. There was 1 case of grade 1 skin acute GvHD which was determined not be related to the therapy In terms of response, the 2 patients that received placebo were partial responders (improved symptoms or undetectable virus) while most patients (n = 9, 64%) were complete responders (improved symptoms and undetectable virus). Investigators found an increase from low levels of virus-specific T-cells after infusion of ALVR106.¹

“There seems to be antiviral activity although the trial was not powered for that. These data are taken, certainly by me, as supporting looking at these therapies and specifically ALVR106 more, for the treatment of respiratory viruses in immunocompromised patients. I think the challenge going forward will be, when do you catch the viral infection, when do you catch the patient, and with that combo, when is there the right patient that has this immune deficit that you can really do them benefit by bridging with this therapy, and I think that’ll be the next rounds of trial design,” Nikiforow concluded.

Nikiforow also noted that the program had been shut down before moving on to phase 2 and any future evaluations on ALVR106 are uncertain. As a company, AlloVir’s future itself is uncertain after it shut down 3 phase 3 trials of its then lead virus specific T-cell therapy, posoleucel, which the company found were unlikely to meet their primary endpoints. Since then, the company has announced that it would lay off 95% of its staff and is now also facing a class action lawsuit for supposedly misleading investors about the potential prospects of posoleucel.^2,3

Read more coverage of the 2024 Tandem meeting now.

REFERENCES

1. Nikiforow S, Horwitz M, McCarty JM, et al. ALVR106, an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Treatment of Respiratory Viral Infections: Results from a Phase 1, First-in-Human, Dose-Ranging Trial. Presented at: 2024 Tandem Meetings, February 21-24, San Antonio, Texas. Abstract #99
2. AlloVir shedding 95% of its staff after discontinuing T cell therapy trials. https://www.marketwatch.com/story/allovir-shedding-95-of-its-staff-after-discontinuing-t-cell-therapy-trial-56302f9e
3. Levi & Korsinsky Notifies Shareholders of AlloVir, Inc.(ALVR) of a Class Action Lawsuit and an Upcoming Deadline. News release. Levi & Korsinsky. February 23, 2024. https://www.wric.com/business/press-releases/cision/20240223NY43749/levi-korsinsky-notifies-shareholders-of-allovir-inc-alvr-of-a-class-action-lawsuit-and-an-upcoming-deadline/mit