Actimmune (interferon gamma-1 b)

P2, N=200, Recruiting, Radboud University Medical Center | Trial completion date: Jan 2025 --> Jun 2027 | Trial primary completion date: Jan 2025 --> Jan 2027

P2, N=45, Recruiting, Sawa Ito, MD | Trial primary completion date: Aug 2026 --> Oct 2027

P1/2, N=7, Terminated, Fred Hutchinson Cancer Center | Trial completion date: Jan 2025 --> Jan 2024 | Active, not recruiting --> Terminated; Terminated due to insufficient funding

P2, N=45, Recruiting, Sawa Ito, MD | Not yet recruiting --> Recruiting

P2, N=45, Not yet recruiting, Sawa Ito, MD

P1/2, N=7, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting | N=16 --> 7 | Trial completion date: Apr 2025 --> Jan 2025 | Trial primary completion date: Apr 2024 --> Jan 2024

P1, N=8, Completed, Sawa Ito, MD | Recruiting --> Completed

We propose a novel mechanism by which AMG 330-activated T cells prime and sensitize AML target cells in a forward feedback loop towards STING activation, leading to increased type-I-IFN production and induction of ISGs. The beneficial effect of physiological cGAMP in enhancing AMG 330-mediated cytotoxicity was accompanied by the pronounced expression of effector cytokines and an overall cytotoxic T-cell phenotype. We established a key role for interferon gamma in AMG 330-mediated cytotoxicity of AML cells and in rendering AML cells responsive to STING agonism.

Bispecific T-cell recruiting antibody constructs (BsAb) have shown clinical efficacy with Blinatumomab, a CD3xCD19 BiTE® construct used for the treatment of relapsed or refractory B-cell precursor ALL...Secretome analyses indicated TGF-β as a prominent cytokine leading to an impairment of T-cell function. Further studies are needed to understand the influence of p53 on the TGF-β pathway in AML cells.

P2, N=28, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Apr 2024 --> Mar 2023

P1/2, N=16, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 --> Apr 2025 | Trial primary completion date: Dec 2025 --> Apr 2024

P1, N=6, Recruiting, Sawa Ito, MD | Trial completion date: Jun 2023 --> Oct 2023 | Trial primary completion date: Jun 2023 --> Oct 2023

P2, N=28, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2023 --> Apr 2024

P1/2, N=51, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed | Trial completion date: Jun 2023 --> Feb 2023

P1, N=6, Recruiting, Sawa Ito, MD | Trial completion date: Mar 2023 --> Jun 2023 | Trial primary completion date: Mar 2023 --> Jun 2023

P1, N=6, Recruiting, Sawa Ito, MD | Trial completion date: Dec 2022 --> Mar 2023 | Trial primary completion date: Dec 2022 --> Mar 2023

IFN-γ (Actimmune®, Horizon Therapeutics) was given as monotherapy for 4 weeks, followed by DLI and IFN-γ for up to 8 additional weeks... This is the first study to show safety and tolerability of IFN-γ in alloSCT recipients. We observed durable remissions in all patients who received IFN-γ and DLI. We are continuing to enroll in the phase I trial with a shortened IFN-γ monotherapy period and are designing a phase II multicenter trial to evaluate efficacy.

The study had two stages: IFN-γ monotherapy (stage 1) with a fixed dose of IFN-γ (ACTIMMUNE®, Horizon Therapeutics) 100 mcg subcutaneously 3 times per week (outpatient self-injection) for 4 weeks and subsequent DLI combined with IFN-γ (stage 2) for 8 more weeks... IFN-g was safe in this pilot cohort of subjects with relapsed AML/MDS post-alloSCT. To our knowledge, this is the first time that IFN-γ has been tested on such subjects. In vivo, IFN-γ induced the predicted changes in myeloblasts.

P2, N=28, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2022 --> Apr 2023

P1, N=6, Recruiting, Sawa Ito, MD | Trial completion date: Jul 2022 --> Dec 2022 | Trial primary completion date: Jul 2022 --> Dec 2022

P1/2, N=51, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jun 2022 --> Jun 2023

P1, N=6, Recruiting, Sawa Ito, MD | Trial completion date: Jan 2022 --> Jul 2022 | Trial primary completion date: Dec 2021 --> Jul 2022

P1, N=18, Terminated, National Cancer Institute (NCI) | Completed --> Terminated; Study was closed to accrual due to lack of drug supply.

P2, N=28, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2021 --> Apr 2022

P1, N=6, Recruiting, University of Pittsburgh | Not yet recruiting --> Recruiting

P1, N=6, Not yet recruiting, University of Pittsburgh | Initiation date: Nov 2020 --> Feb 2021

P1/2, N=52, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

P1, N=6, Not yet recruiting, Sawa Ito, MD

P1, N=18, Completed, National Cancer Institute (NCI) | Recruiting --> Completed | N=40 --> 18 | Trial completion date: Jul 2023 --> Sep 2020 | Trial primary completion date: Apr 2022 --> Sep 2020