P1/2, N=215, Active, not recruiting, NeoImmuneTech | Trial completion date: Mar 2025 --> Dec 2024

P1, N=30, Not yet recruiting, Washington University School of Medicine

P2, N=47, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> Apr 2024

This study provides a rationale for NT-I7 plus CAR-T cell combination therapy for solid tumors in humans.

P1, N=10, Recruiting, Hyunseok Kang, MD | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

P1, N=72, Completed, Astellas Pharma Global Development, Inc. | Active, not recruiting --> Completed

Notably, TCE treatment has no major effect on tumor-reactive CD8 TILs. Our results suggest that rhIL-7-hyFc treatment promotes the antitumor efficacy of TCE immunotherapy by increasing TCE-sensitive bystander CD8 TILs in solid tumors.

P2, N=8, Terminated, Revimmune | N=12 --> 8 | Trial completion date: Dec 2022 --> Mar 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2022 --> Dec 2023; non convincing results

P2, N=10, Terminated, Revimmune | Active, not recruiting --> Terminated; POOR ACCRUAL

P1, N=10, Terminated, NeoImmuneTech | Phase classification: P2 --> P1

P1, N=78, Recruiting, SL VAXiGEN

rhIL-7-hyFc can expand and maintain the progenitor pool of exhausted CD8+ T cells, whereas hIL-2/TCB2c promotes their differentiation into TEX term. Together, this induces an immune-stimulatory TME that improves the efficacy of checkpoint blockade.

P1/2, N=215, Active, not recruiting, NeoImmuneTech | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Nov 2024 | Recruiting --> Active, not recruiting

P2, N=160, Active, not recruiting, I-Mab Biopharma Co. Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Nov 2023 --> Dec 2024

P2, N=56, Recruiting, Yonsei University | N=25 --> 56 | Trial primary completion date: Dec 2025 --> Aug 2025

P1/2, N=84, Completed, Genexine, Inc. | Phase classification: P1b/2 --> P1/2

P1/2, N=31, Terminated, NeoImmuneTech | Phase classification: P1b/2a --> P1/2 | N=84 --> 31 | Trial completion date: May 2024 --> Aug 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2024 --> Aug 2023; Strategic decision by sponsor

P1, N=57, Recruiting, NeoImmuneTech | Phase classification: P1b --> P1

P1, N=72, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Aug 2024 --> Apr 2024 | Trial primary completion date: Aug 2024 --> Apr 2024

P2, N=133, Active, not recruiting, I-Mab Biopharma Co. Ltd. | Recruiting --> Active, not recruiting

P1/2, N=70, Recruiting, Washington University School of Medicine | Trial completion date: Jan 2030 --> Jan 2032 | Trial primary completion date: Jan 2030 --> Jan 2032

P1, N=8, Terminated, Fred Hutchinson Cancer Center | Active, not recruiting --> Terminated; Terminated due to end of funding

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.

Treatment of patients with GC/GEJC with GEN-001 in combination with avelumab in the ≥ 3L setting showed promising antitumor activities with an overall manageable safety profile. The results from this trial will be updated about its effects on clinical outcome, including survival, safety, and biomarker findings. Clinical trial information: NCT05419362.

To evaluate the impact of CD2 on CAR-T function, we generated CD19 CAR-T cells (UCART19) with or without CD2 deletion, single-cell secretome analysis revealed that CD2 deletion in UCART19 reduced frequencies of the effector cytokines (Granzyme-B and IFN-γ). Treatment with rhIL-7-hyFc prolonged UCART2 persistence and increased survival in both the tumor re-challenge model and primary patient T-ALL model in vivo. Together, these data suggest that allogeneic fratricide-resistant UCART2, in combination with rhIL-7-hyFc, could be a suitable approach for treating T-cell malignancies.

P1/2, N=238, Recruiting, NeoImmuneTech | Phase classification: P1b/2a --> P1/2

Timing the oncolytic ZIKV injection with the peak in peripheral CD8+ T-cells greatly improved survival in the immunotherapy resistant SB28 glioma model. These data suggest a role for NT-I7 as an adjunct to various T-cell mediated treatment strategies for GBM.

This study opened in Jan 2023. Six (6) of the planned thirty (30) patients had been enrolled by time of submission.

P1, N=0, Withdrawn, National Cancer Institute (NCI) | N=68 --> 0 | Trial completion date: Feb 2024 --> Nov 2023 | Active, not recruiting --> Withdrawn | Trial primary completion date: Feb 2024 --> Nov 2023

The novel peptide agonist reported here scores very low in predicted immunogenicity, and because the peptide lacks sequence similarity with IL-7, the problematic immunogenic neutralization of endogenous cytokine should not occur. The properties we report here implicate MDK-703 as a candidate for clinical evaluation in oncology, anti-viral and other infectious disease, vaccine enhancement, and treatment of lymphopenia.

P2, N=47, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Oct 2024 | Trial primary completion date: Dec 2023 --> Sep 2023

P2; Recruiting --> Active, not recruiting

P2, N=42, Active, not recruiting, Genome & Company | Recruiting --> Active, not recruiting

P2, N=148, Recruiting, Genome & Company | Not yet recruiting --> Recruiting

P1, N=8, Active, not recruiting, Fred Hutchinson Cancer Center | Trial completion date: Apr 2024 --> Nov 2023 | Trial primary completion date: Apr 2024 --> Nov 2023

P1, N=12, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Terminated; Terminated [NCI decided to terminate ABTC Consortium due to NCI moving in different direction for Brain Cancer]

Conclusions NT-I7-driven T cell expansion, even when combined with an anti-PD-1 agent like pembrolizumab, promotes stemness and restores T cell fitness in heavily pretreated subjects showing signs of immune dysfunction. Combining NT-I7 with conventional immunotherapy or other anticancer agents has added systemic benefits that could impact long-term clinical response in these patients.

In recent years, the progression-free survival and overall survival of patients suffering from gliomas significantly increased by introducing C7R-expressing chimeric antigen receptor (CAR)-T cells and long-acting IL-7 agonists such as NT-I7 (rhIL-7-hyFc, Efineptakin alfa)...This article first reviews the pathophysiological roles of IL-7/IL-7R in tumors, focusing on gliomas. Subsequently, it discusses the therapeutic values of IL-7/IL-7R and the recombinant derivatives in gliomas.

P2, N=42, Recruiting, Genome & Company | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

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.

P2; Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Sep 2023 --> Sep 2024