FDA Grants Orphan Drug Designation to SIRPant-M in T-Cell Lymphoma

The FDA has granted an orphan drug designation to SIRPant-M™ (SI-101) as a potential therapeutic option for patients with T-cell lymphoma, according to an announcement from SIRPant Immunotherapeutics.¹

The autologous SIRPαlow-activated macrophage therapy is manufactured using PhagoAct™, a non-genetic method designed to modulate SIRPα expression and simultaneously instruct endogenous macrophages to identify and eradicate aggressive tumors following administration.

SIRPant-M directly targets malignant cells through the activation of cytotoxic T cells and the production of antibodies specific to cancer neoantigens. Additionally, SIRPant-M reduces immunosuppressive factors, promoting a pro-inflammatory tumor microenvironment. Through this multimodal approach, SIRPant-M could promote persistent and enduring immune memory that decreases the likelihood of a patient experiencing relapse.

The agent can be employed either as a monotherapy or in conjunction with other immuno-stimulatory modalities such as radiotherapy and immune checkpoint inhibitors.

“Unlike B-cell lymphomas and classical Hodgkin lymphoma, many T-cell lymphoma subtypes do not have a suitable drug target, and approved cellular immunotherapy is currently unavailable in T-cell lymphoma,” Jelle Kijlstra, MD, MBA, chief medical officer of SIRPant Immunotherapeutics, stated in a news release. “With its unique polyclonal mechanism of action, relying on tumor-specific neoantigens, SIRPant-M is well positioned to reveal the therapeutic potential of macrophage cell therapy in our recently opened clinical trial.”

Preclinical data with SIRPant-M indicate that the agent demonstrates efficacy in hematological tumors, as well as a variety of solid tumors in vivo. Accordingly, SIRPant Immunotherapeutics anticipates the filing of a second investigational new drug application for the investigation of SIRPant-M in solid tumors, specifically focused on head and neck cancers.²

This therapy is currently being evaluated in a first-in-human phase 1 trial (NCT05967416) as a treatment of patients with relapsed/refractory non-Hodgkin lymphoma (NHL).^2,3 In this trial, the agent will be administered either alone or in combination with 2.5 Gy of low-dose focal external-beam radiotherapy to eligible patients with B-cell NHL and select patients with T-cell NHL.³

Eligible patients include those 18 years of age or older with histologically or cytologically confirmed NHL who received at least 2 lines of systemic therapy, are ineligible or unable to receive other curative therapies, and have recovered from any acute toxic effects associated with prior therapy. Patients must not have been previously undergone ITI therapy; must not have received an autologous stem cell transplant or CAR-T cell therapy within 1 month of enrollment; must not have received an allogeneic stem cell transplant within 6 months of study treatment; and must not have received prior systemic anti-cancer therapy up to 14 days before treatment initiation.

Autologous SIRPant-M will be delivered every 2 days through 3 equal intratumoral injections. Two dose levels will be evaluated: 90 x 106 cells and 300 x 106 cells. Patients in the combination cohort will receive 2.5 Gy of radiation after each dose of SIRPant-M, for a total of 7.5 Gy radiation. The study will employ a 3+3 design to stagger dose escalations.

The study’s primary objective is to evaluate the safety and tolerability of SIRPant-M alone or in combination with radiation. Key secondary end points include identification of the recommended phase 2 dose of SIRPant-M and objective response rate.

“Allowance of Orphan Drug Designation represents a significant milestone for the Company and is important recognition for the promise of our therapeutic platform,” said Robert Towarnicki, CEO of SIRPant, in the news release.

References

1. SIRPant Immunotherapeutics receives FDA orphan drug designation for SIRPant-M for the treatment of T-cell lymphoma. News release. SIRPant Immunotherapeutics. November 15, 2023. Accessed November 15, 2023. https://sirpantimmunotx.com/news/sirpant-immunotherapeutics-receives-fda-orphan-drug-designation-for-sirpant-m-for-the-treatment-of-t-cell-lymphoma/
2. SIRPant Immunotherapeutics announces FDA clearance of IND application for SIRPant-M™ autologous SIRPαlow activated macrophage immunotherapy. News release. SIRPant Immunotherapeutics. May 1, 2023. Accessed November 15, 2023. https://sirpantimmunotx.com/news/sirpant-immunotherapeutics-announces-fda-clearance-of-ind-application-for-sirpant-m-autologous-sirp%CE%B1low-activated-macrophage-immunotherapy/
3. Study of SIRPant-M in participants with Relapsed or refractory non-Hodgkin's lymphoma. ClinicalTrials.gov. Updated September 13, 2023. Accessed November 15, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05967416