CYT107 / Revimmune - LARVOL DELTA

Potential of interleukin-7 in sepsis as a biomarker and therapeutic agent: a narrative review. (PubMed, Front Med (Lausanne)) - "We searched PubMed, Embase, and Web of Science from inception to April 24, 2025, using terms such as Interleukin-7, CD127, CYT107, interleukin-7 receptor, sepsis, septic shock, and lymphopenia...Exogenous IL-7 may modulate immune function in patients with clinical sepsis but does not reduce mortality. Endogenous IL-7 is closely associated with sepsis, whereas exogenous IL-7 shows promise for aiding the recovery of patients with sepsis, although further research is required."

Biomarker • Journal • Review • Infectious Disease • Inflammation • Septic Shock • IL7 • IL7R

Impact of Recombinant Human Interleukin-7 (CYT107) on Tumor Clearance and Immune Reconstitution in Multiple Myeloma Patients After Autologous Hematopoietic Cell Transplant (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Recent advances of precision immunotherapy in sepsis. (PubMed, Burns Trauma) - "Suggested strategies to attenuate the immune responses are anakinra, nangibotide and tocilizumab...Suggested strategies to restore SII are nivolumab, recombinant human interferon-gamma, CYT107, granulocyte macrophage colony stimulating factor and IgM-enriched immunoglobulin prepapations. Biomarkers that guide their use are the expression of the human leukocyte antigen DR on blood monocytes, the absolute lymphocyte count and blood levels of immunoglobulin M. One recently suggested strategy to restore vascular tone is adrecizumab, the use of which is guided by blood levels of bio-adrenomedulin. The use of these precision treatment strategies is still hampered by the need for large-scale randomized controlled trials."

IO biomarker • Journal • Review • Infectious Disease • Septic Shock • CRP • IFNG

A randomized, double-blind, placebo controlled trial of IL-7 in critically ill COVID-19 patients. (PubMed, JCI Insight) - P2 | "Given that hospital-acquired infections are responsible for a large percentage of COVID-19 deaths, this effect of CYT107 to decrease nosocomial infections could substantially reduce late morbidity and mortality in this highly lethal disease. The strong safety profile of CYT107 and its excellent tolerability provide support for trials of CYT107 in other potential pandemic respiratory viral infections."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • CD4 • CD8 • IFNG • IL7

A Phase II Open-Label, Randomized Clinical Trial of Atezolizumab with or without Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer (Clin Cancer Res) - P2 | N=47 | NCT03513952 | "CYT107 plus atezolizumab was well-tolerated, without dose-limiting toxicities and lower grade 3 to 4 treatment-related adverse events compared with atezolizumab monotherapy. The ORR was 26.3% for the combination therapy versus 23.8% for atezolizumab alone (P = 0.428). The complete response rate was 10.5% for the combination therapy versus 4.8% for monotherapy. Three patients on combination therapy had responses >21 months versus one with monotherapy. CD4+ and CD8+ T-lymphocyte expansion occurred in patients with response to combination therapy, with the greatest effect in T memory stem cells."

P2 data • Urothelial Cancer

A phase II open label, randomized clinical trial of atezolizumab with or without human recombinant IL-7 (CYT107) in advanced urothelial cancer. (PubMed, Clin Cancer Res) - "Combining CYT107 with atezolizumab was safe and resulted in lymphocyte expansion, a doubling of the CR rate, and durable responses exceeding 2 years, however, the ORR was similar to atezolizumab alone. Increased and sustained doses of CYT107 coupled with patient selection strategies should be further investigated."

Clinical • Journal • Metastases • P2 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD4 • CD8 • IL7

Impact of Recombinant Human Interleukin-7 (CYT107) on Tumor Clearance and Immune Reconstitution in Multiple Myeloma Patients After Autologous Hematopoietic Cell Transplant (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Oct 2028 ➔ Jan 2029 | Initiation date: Oct 2024 ➔ Jan 2025 | Trial primary completion date: Oct 2028 ➔ Jan 2029

Trial completion date • Trial initiation date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=47 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Apr 2024

Metastases • Trial completion • Trial completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urothelial Cancer • CD4 • IFNG • PD-L1

Impact of Recombinant Human Interleukin-7 (CYT107) on Tumor Clearance and Immune Reconstitution in Multiple Myeloma Patients After Autologous Hematopoietic Cell Transplant (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

IMPULSE-7: Recombinant Interleukin-7 (CYT107) to Treat Patients With Refractory Nontuberculous Mycobacterial Lung Disease (clinicaltrials.gov) - P2 | N=8 | Terminated | Sponsor: Revimmune | N=12 ➔ 8 | Trial completion date: Dec 2022 ➔ Mar 2024 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2022 ➔ Dec 2023; non convincing results

Enrollment change • Nontuberculous mycobacteria • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • CD4 • CD8 • IFNG • IL10 • IL6 • IL7 • PD-1 • TNFA

InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic Patients With COVID-19 Infection ( ILIAD-7-US-O ) (clinicaltrials.gov) - P2 | N=10 | Terminated | Sponsor: Revimmune | Active, not recruiting ➔ Terminated; POOR ACCRUAL

Trial termination • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Oncology

A randomized phase II study of atezolizumab (atezo) plus recombinant human IL-7 (CYT107) in patients with locally advanced or metastatic urothelial carcinoma. (ASCO-GU 2024) - P2 | "This is the first randomized trial of atezo +/- IL-7 (CYT107) in mUC. During the trial, the FDA approval for atezo in mUC was withdrawn, which limited enrollment. However, our results show that the addition of CYT107 to atezo is safe/tolerable, with comparable toxicity profile and efficacy to monotherapy."

Clinical • Metastases • P2 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • IL7

A randomized phase II study of atezolizumab (atezo) plus recombinant human IL-7 (CYT107) vs. atezo alone in patients with locally advanced or metastatic urothelial carcinoma (mUC) (ESMO 2023) - P2 | "During the trial, the FDA approval for atezo in mUC was withdrawn, which limited enrollment. However, our results show that the addition of CYT107 to atezo is safe/tolerable, although there was no improvement in clinical outcomes compared to atezo monotherapy."

Clinical • Metastases • P2 data • Oncology • Solid Tumor • Urothelial Cancer • IL7

Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=47 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2023 ➔ Oct 2024 | Trial primary completion date: Dec 2023 ➔ Sep 2023

Metastases • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urothelial Cancer • CD4 • PD-L1

ESMO 2023: A Randomized Phase II Study of Atezolizumab plus Recombinant Human IL-7 (CYT107) Versus Atezolizumab Alone in Patients with Locally Advanced or Metastatic Urothelial Carcinoma (Urotoday) - P2 | N=54 | NCT03513952 | "The 2023 ESMO annual meeting included a session on urothelial carcinoma, featuring a presentation by Dr. Russell Pachynski discussing a randomized phase II study of atezolizumab + recombinant human IL-7 (CYT107) versus atezolizumab alone in patients with locally advanced or metastatic urothelial carcinoma....ORR was 26.3% for the combination versus 23.8% for atezolizumab alone (p=0.43). There were no significant differences in clinical benefit rate, PFS, DOR, or OS, and no dose limiting toxicities were seen in the safety run-in cohort (n = 7). Overall, 76.9% (20/26) of patients on the CYT107 arm received all four doses. The combination of CYT107 and atezolizumab was well tolerated compared to the atezolizumab arm, with overall grade 3-4 adverse events occurring in 46.2% (12/26) and 63.2% (12/19), respectively."

P2 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Intravenously administered interleukin-7 to reverse lymphopenia in patients with septic shock: a double-blind, randomized, placebo-controlled trial. (PubMed, Ann Intensive Care) - P2 | "Intravenous CYT107 reversed sepsis-induced lymphopenia. However, compared to intramuscular CYT107 administration, it was associated with transient respiratory distress without long-term sequelae. Because of equivalent positive laboratory and clinical responses, more favorable pharmacokinetics, and better patient tolerability, intramuscular administration of CYT107 is preferable."

Journal • Lymphopenia • Infectious Disease • Septic Shock • CD4 • CD8 • IL7

Recombinant Human Interleukin-7 to Promote T-Cell Recovery After Haploidentical or Cord Blood Stem Cell Transplant (clinicaltrials.gov) - P1/2 | N=1 | Completed | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Completed | N=21 ➔ 1 | Trial completion date: Dec 2023 ➔ Mar 2023 | Trial primary completion date: Dec 2023 ➔ Mar 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Transplantation

Recombinant Human Interleukin-7 to Promote T-Cell Recovery After Haploidentical or Cord Blood Stem Cell Transplant (clinicaltrials.gov) - P1/2 | N=21 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Transplantation

Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=54 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Metastases • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urethral Cancer • Urothelial Cancer • CD4 • PD-L1

Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=54 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urethral Cancer • Urothelial Cancer • CD4 • PD-L1

Recombinant Human Interleukin-7 to Promote T-Cell Recovery After Haploidentical or Cord Blood Stem Cell Transplant (clinicaltrials.gov) - P1/2 | N=21 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Phase classification: P1 ➔ P1/2

Phase classification • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Transplantation

InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic Patients With COVID-19 Infection ( ILIAD-7-US-O ) (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: Revimmune | Recruiting ➔ Active, not recruiting | N=48 ➔ 10 | Trial completion date: Dec 2021 ➔ Jun 2022 | Trial primary completion date: Dec 2021 ➔ Jun 2022

Clinical data • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Oncology • CD4 • CD8

InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection ( ILIAD-7-US-I ) (clinicaltrials.gov) - P2 | N=26 | Terminated | Sponsor: Revimmune | N=48 ➔ 26 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2021 ➔ Mar 2022; POOR ACCRUAL

Clinical data • Enrollment change • Trial primary completion date • Trial termination • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • CD4 • CD8

ILIAD-7-FR: InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection FR BL Cohort (clinicaltrials.gov) - P2 | N=34 | Terminated | Sponsor: Revimmune | Trial completion date: Dec 2021 ➔ Mar 2022 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2021 ➔ Mar 2022; poor accrual

Clinical data • Trial completion date • Trial primary completion date • Trial termination • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • CD4 • CD8

ILIAD-7 BRA: InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection (Brazil Cohort) (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor: Revimmune | N=48 ➔ 4 | Trial completion date: Jun 2022 ➔ Mar 2022 | Recruiting ➔ Terminated; POOR ACCRUAL

Clinical data • Enrollment change • Trial completion date • Trial termination • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • CD4 • CD8