Hyleukin-7 (efineptakin alfa)

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

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.

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

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

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

P2; Recruiting --> Active, not 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; Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Sep 2023 --> Sep 2024

Further, in CRS in vitro assays, CAR-iNKT induced less IL-6 than CAR-T, suggesting reduced likelihood for CAR-iNKT cell therapy to induce CRS in patients. These data suggest BCMA CAR-iNKT are potentially a safer, effective alternative to BCMA-CAR-T and BCMA CAR-iNKT efficacy is further potentiated with rhIL-7-hyFc.

P1, N=68, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | Trial completion date: May 2025 --> Feb 2024

P1, N=8, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting | N=20 --> 8 | Trial primary completion date: Dec 2023 --> Apr 2024

P2, N=34, Suspended, Mayo Clinic | Active, not recruiting --> Suspended

P1b/2, N=84, Completed, Genexine, Inc. | Active, not recruiting --> Completed | Trial completion date: Apr 2024 --> May 2023

P2, N=34, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting

"Lunit...announced the presentation of 16 abstracts featuring its AI-biomarker platform at the American Society of Clinical Oncology (ASCO) Annual Meeting, to be held in Chicago, Illinois, on June 2-6."

P2; Not yet recruiting --> Recruiting

NT-I7 as an adjuvant to a DNA neoantigen vaccine increases the magnitude and duration of neoantigen-specific anti-tumor immunity in a murine model. Clinical application of NT-I7 may help overcome immunologic shortcomings of current neoantigen vaccines.

P1b/2a, N=84, Active, not recruiting, NeoImmuneTech | Recruiting --> Active, not recruiting

P1, N=20, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Jun 2025 --> Mar 2024

P1, N=12, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2022 --> Oct 2023

P1/2, N=70, Recruiting, Washington University School of Medicine | Trial completion date: Jul 2028 --> Jan 2030 | Trial primary completion date: Jul 2028 --> Jan 2030

Our study reports that IL-7 immunotherapy can restore and maintain TLC during treatment with various salvage chemotherapies in recurrent GBM patients without serious toxicity.