Viralym-M (posoleucel) / Kalaris Therapeutics - LARVOL DELTA

Posoleucel for BK Polyomavirus in Kidney Transplant Recipients. (PubMed, J Am Soc Nephrol) - No abstract available

Journal • Transplantation

Posoleucel (ALVR105, Formerly Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=26 | Completed | Sponsor: AlloVir | Active, not recruiting ➔ Completed

Trial completion • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Infectious Disease • Transplantation • CD4 • HLA-B • HLA-C

Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients. (PubMed, Cytotherapy) - P2, P2/3, P3 | "Our results demonstrate that posoleucel is enriched for central and effector memory CD4+ and CD8+ T cells with specificity for posoleucel target viruses and expressing a broad repertoire of T cell receptors. Antigen-driven upregulation of cell-surface molecules and production of cytokine and effector molecules indicative of proliferation, co-stimulation, and cytolytic potential demonstrate the specificity of posoleucel and its potential to mount a broad, polyfunctional, and effective Th1-polarized antiviral response upon viral exposure. We also show the low risk for off-target and nonspecific effects as evidenced by the enrichment of posoleucel in memory T cells, low frequency of naive T cells, and lack of demonstrated alloreactivity in vitro. The efficacy of posoleucel is being explored in four placebo-controlled clinical trials in transplant recipients to treat and prevent viral infections (NCT05179057, NCT05305040, NCT04390113, NCT04605484)."

Clinical • Journal • Virus specific T cells • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Infectious Disease • Solid Organ Transplantation • Transplantation • CD4 • CD8

Final Outcomes from a Phase 2 Trial of Posoleucel in Allogeneic Hematopoietic Cell Transplant Recipients. (PubMed, Blood Adv) - P2/3 | "Repeat posoleucel dosing was generally safe and well tolerated and associated with functional immune reconstitution. www.clinicaltrials.gov NCT04693637."

Journal • P2 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Transplantation • IFNG

Posoleucel in Kidney Transplant Recipients with BK Viremia: Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. (PubMed, J Am Soc Nephrol) - "Posoleucel was generally safe, well tolerated, and associated with a larger reduction of BK viremia compared to placebo. Limitations of this study include the relatively short duration of follow-up and lack of power to detect significant differences in clinical outcomes."

Clinical • Journal • P2 data • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Transplant Rejection • Transplantation

Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=378 | Terminated | Sponsor: AlloVir | Trial completion date: Dec 2024 ➔ Jan 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Jan 2024; Study discontinued as DSMB determined it was futile. No safety concerns were noted.

Trial completion date • Trial primary completion date • Trial termination • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Infectious Disease • Transplantation • HLA-B

Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation (clinicaltrials.gov) - P3 | N=51 | Terminated | Sponsor: AlloVir | N=80 ➔ 51 | Trial completion date: Jun 2024 ➔ Jan 2024 | Recruiting ➔ Terminated; Study discontinued as DSMB determined it was futile. No safety concerns were noted.

Enrollment change • Trial completion date • Trial termination • Infectious Disease • Pediatrics • Transplantation

Study to Evaluate Viralym-M (ALVR105) for the Treatment of Virus-Associated Hemorrhagic Cystitis (HC) (clinicaltrials.gov) - P3 | N=97 | Terminated | Sponsor: AlloVir | Trial completion date: Jun 2024 ➔ Jan 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2024 ➔ Jan 2024; Study discontinued as DSMB determined it was futile. No safety concerns were noted.

Trial completion date • Trial primary completion date • Trial termination • Hematological Disorders • Infectious Disease • Transplantation

Phenotypic and Functional Characterization of Posoleucel, a Multivirus-Specific T Cell Therapy for the Treatment and Prevention of Viral Infections in Immunocompromised Patients (TCT-ASTCT-CIBMTR 2024) - P2, P2/3, P3 | "PSL is enriched for central and effector memory CD4+ and CD8+ T cells that contain a broad repertoire of TCRs with specificity for AdV, BKV, CMV, EBV, HHV-6 and JCV. Upregulation of cell-surface molecules and production of effectors indicative of proliferation, co-stimulation and cytolytic potential show that PSL can mediate a diverse and effective antiviral response. Furthermore, PSL has a low risk for off-target and alloreactive responses as evidenced by its enrichment in memory T cells, low frequency of naïve T cells, and lack of demonstrated alloreactivity in vitro."

Clinical • IO biomarker • Virus specific T cells • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Infectious Disease • Transplantation • CD28 • CD40LG • CD69 • CD8 • CSF2 • HAVCR2 • IFNG • IL2 • IL2RA • LAG3 • LAMP1 • TNFA

Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=378 | Active, not recruiting | Sponsor: AlloVir | Recruiting ➔ Active, not recruiting

Enrollment closed • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Infectious Disease • Transplantation • HLA-B

FINAL CLINICAL AND BIOMARKER DATA FROM A PHASE 2 TRIAL OF POSOLEUCEL, AN OFF-THE-SHELF, MULTIVIRUS-SPECIFIC T-CELL THERAPY, FOR PREVENTION OF CLINICALLY SIGNIFICANT VIRAL INFECTIONS POST-HCT (EBMT 2023) - P2/3 | "High-risk allo-HCT patients who received posoleucel had lower than expected rates of CSIs from the 6 targeted viruses despite the high incidence of viral reactivations. Repeat dosing of posoleucel was generally safe and well tolerated. Viral control was associated with expansion of functional T cells against multiple infecting viruses during the dosing period with persistence of posoleucel-derived clones confirmed after the infusion period."

Biomarker • Clinical • IO biomarker • P2 data • Virus specific T cells • Acute Graft versus Host Disease • Allergy • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Transplantation

Posoleucel Associated with Reduction of BK Viremia and Persistence of BK-Reactive T Cells in a Phase 2 Trial (KIDNEY WEEK 2023) - P2 | "PSL was generally safe & well tolerated. Clinically meaningful BK VL reductions & increases in BK-reactive T cells were seen in PSL pts, particularly those with high VL who are at highest risk for renal impairment."

P2 data • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Transplant Rejection • Transplantation

posoleucel (allogeneic, off-the-shelf, multivirus specific T cells designed to target AdV, BKV, CMV, EBV, HHV-6 and JCV) / AlloVir (IDWeek 2023) - No abstract available

Virus specific T cells • Infectious Disease

Posoleucel Associated With Reduction Of Bk Viremia And Increases In Bk-Reactive T Cells In A Phase 2 Trial (ESOT 2023) - P2 | N=61 | (NCT04605484) | Sponsor: AlloVir | "PSL was generally safe and well tolerated. Clinically meaningful BK VL reductions and increases in BK-reactive T cells occurred in PSL patients. PSL was detected during dosing and for up to 12 wks after infusion period, which is the first demonstration of PSL persistence in KT patients."

Late-breaking abstract • P2 data

Study of Posoleucel (Formerly Known as ALVR105; Viralym-M) in Kidney Transplant Patients With BK Viremia (clinicaltrials.gov) - P2 | N=61 | Completed | Sponsor: AlloVir | Active, not recruiting ➔ Completed | Trial completion date: Mar 2023 ➔ Oct 2022 | Trial primary completion date: Mar 2023 ➔ Oct 2022

Trial completion • Trial completion date • Trial primary completion date • Virus specific T cells • Infectious Disease • Renal Disease • Transplantation

Posoleucel for BKV Infection in Kidney Transplant Patients: Final Results from Randomized, Placebo-Controlled Phase 2 Trial (ATC 2023) - P2 | "PSL was generally safe and well tolerated. Clinically meaningful BK VL reductions occurred in patients treated with PSL, particularly among patients with high VL who are at highest risk for renal impairment. Continued clinical development of PSL in KT recipients is warranted."

Clinical • Late-breaking abstract • P2 data • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Transplant Rejection • Transplantation

Posoleucel (ALVR105), an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Prevention of Viral Infections Post-HCT: Results from an Open-Label Cohort of a Phase 2 Trial (ASH 2021) - P2 | "Those with grade ≥3 GVHD as well as those requiring steroids (>0.5 mg/kg/day prednisone equivalent) at enrollment are ineligible...This patient was administered IV cidofovir in week 15 of the study. During the primary study efficacy period one participant received 2 doses of valganciclovir following transient CMV viremia deemed not to be clinically significant by the principal investigator... Preliminary results in this open-label cohort show that in high-risk allo-HCT patients receiving off-the-shelf posoleucel, clinically significant viral infections or disease from the 6 targeted dsDNA viruses were uncommon. No clinically significant infections were observed among participants treated in accordance with the protocol. These results, combined with the favorable safety and tolerability profile of posoleucel, support its continued evaluation in high-risk allo-HCT recipients for the prevention of CMV, EBV, HHV6, AdV, BK virus, or JC virus infection and disease."

Clinical • P2 data • Acute Graft versus Host Disease • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Transplantation • CD4

Posoleucel (ALVR105), an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Prevention of Viral Infections Post-Allogeneic Hematopoietic Cell Transplantation (allo-HCT): Results from an Open-Label Cohort of a Phase 2 Trial (TCT-ASTCT-CIBMTR 2022) - P2 | "This patient received IV cidofovir in study week 15. One patient received 2 doses of valganciclovir following transient CMV viremia deemed not clinically significant by the principal investigator... In this open-label cohort, clinically significant viral infections or disease from the 6 targeted viruses were uncommon in high-risk allo-HCT patients receiving off-the-shelf posoleucel. These results, combined with the favorable safety and tolerability profile of posoleucel, support its continued evaluation for the prevention of CMV, EBV, HHV-6, AdV, BK virus, or JC virus infection."

Clinical • P2 data • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Transplantation • CD4

POSOLEUCEL FOR THE PREVENTION OF CLINICALLY SIGNIFICANT INFECTIONS IN HIGH-RISK ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS: DESIGN OF A PHASE 2/3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL (EBMT 2022) - P2 | "High risk allo-HCT is defined as receiving a transplant from a mismatched related donor, haploidentical donor, unrelated donor, cord blood donor, or undergoing T cell depletion from ATG, alemtuzumab, or ex-vivo graft manipulation.  This phase 3 trial cohort will provide pivotal data on the efficacy and safety of posoleucel compared with placebo for the prevention of clinically significant infection and disease from CMV, EBV, HHV-6, AdV, BKV, and JCV in high risk allo-HCT recipients."

Clinical • P2/3 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Immunology • Infectious Disease • Pediatrics • Transplantation

Final Clinical Outcomes from a Phase 2 Trial of Posoleucel, an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Prevention of Clinically Significant Viral Infections Post-HCT (TCT-ASTCT-CIBMTR 2023) - P2/3 | "High-risk allo-HCT pts who received PSL had lower than expected rates of CSIs from the 6 targeted viruses despite the observed and expected viral reactivations. Repeat dosing of PSL was generally safe and well tolerated. A placebo-controlled phase 3 trial evaluating PSL for the prevention of clinically significant AdV, BKV, CMV, EBV, HHV-6, and JCV infections is ongoing (NCT05305040)."

Clinical • Clinical data • P2 data • Virus specific T cells • Acute Graft versus Host Disease • Allergy • CNS Disorders • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Transplantation • IFNG

POSOLEUCEL, MULTIVIRUS-SPECIFIC T-CELL (VST) THERAPY, FOR PREVENTION OF CLINICALLY SIGNIFICANT VIRAL INFECTIONS IN ALLOGENEIC TRANSPLANT RECIPIENTS: PERSISTENCE OF VSTS IN AN OPEN-LABEL PHASE 2 TRIAL (EBMT 2022) - P2 | " The high-risk allo-HCT recipients receiving posoleucel in this phase 2 open-label trial had low rates of CSI and no EOD. Repeat dosing of posoleucel was generally safe and well tolerated. ELIspot and Immunosequencing data shows in vivo activity of posoleucel in the presence of reactivating viruses."

Clinical • IO biomarker • P2 data • Bone Marrow Transplantation • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Infectious Disease • Transplantation • IFNG

Final Clinical Outcomes from a Phase 2 Trial of Posoleucel, an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Prevention of Clinically Significant Viral Infections Post-HCT (ASH 2022) - P2/3 | "Those with grade ≥3 GVHD and those requiring steroids (>0.5 mg/kg/day prednisone equivalent) at enrollment were ineligible. Results from this open-label phase 2 trial show that high-risk allo-HCT patients who received posoleucel had lower than expected rates of clinically significant viral infections from the 6 targeted viruses despite the observed and expected low-level viral reactivations throughout the study. Repeat dosing of posoleucel was generally safe and well tolerated. Posoleucel VSTs were detected in vivo for up to 26 weeks, and reconstituting T cells demonstrated functional specificity for multiple viruses."

Clinical • Clinical data • P2 data • Acute Graft versus Host Disease • Allergy • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Transplantation • IFNG

AlloVir Announces Positive Final Results from Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Posoleucel in Kidney Transplant Recipients with BK Viremia (Businesswire) - "February 15, 2023, 07:00 AM EST, BKV is one of the most feared transplant-associated viral infections, due to the lack of available effective antiviral therapies and its profoundly negative impact on transplant outcomes,' said Anil K. Chandraker, MD...'The safety profile of posoleucel and its antiviral activity, which is amplified in high viral load patients who have the greatest unmet need, suggest it could potentially offer a transformative treatment option for kidney transplant patients with BK viremia.'"

Live event

Posoleucel Multivirus-Specific T Cell Therapy to Treat Disseminated Adenovirus Infection in a CAR-T Recipient (TCT-ASTCT-CIBMTR 2023) - "Case Background: In June 2022, a 69-year-old woman with relapsed/refractory MM (diagnosed in 2018) received LD chemotherapy containing fludarabine and cyclophosphamide given on Days 1 to 3 before a 2nd round of CAR-T therapy (her first dose was in April 2022)...Urine labs were consistent with acute kidney injury from acute tubular necrosis associated with her severe diarrhea and drug toxicity from cidofovir... The multivirus-specific T cell therapy posoleucel appeared to be safe and effective against refractory disseminated AdV infection in this elderly patient with immune insufficiency as the result of LD chemotherapy and CAR-T."

Virus specific T cells • Acute Kidney Injury • Hematological Disorders • Hematological Malignancies • Infectious Disease • Metabolic Disorders • Multiple Myeloma • Nephrology • Oncology • Renal Disease • CD4 • HLA-B

Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation (clinicaltrials.gov) - P3 | N=80 | Recruiting | Sponsor: AlloVir | Trial completion date: Jan 2024 ➔ Jun 2024

Trial completion date • Infectious Disease • Pediatrics • Transplantation