SIRPant-M Receives FDA Orphan Drug Designation for T-Cell Lymphoma


SIRPant-M has been granted orphan drug designation by the FDA for patients with T-cell lymphoma.

  • The FDA has recognized the potential of SIRPant-M to treat patients with T-cell lymphoma.

  • SIRPant-M is a novel cell therapy that uses SIRPαlow-activated macrophages to target cancer cells.

  • A phase 1 clinical trial (NCT05967416) of SIRPant-M is currently underway in patients with relapsed/refractory non-Hodgkin lymphoma (NHL).

An orphan drug designation has been granted to SIRPant-M (SI-101) by the FDA for patients with T-cell lymphoma, according to SIRPant Immunotherapeutics.1

SIRPant-M is an autologous SIRPαlow-activated macrophage therapy. The product was made using a non-genetic method called PhagoAct, which was created to activate the macrophages in patients for the recognition and elimination of cancer cells.

In combination with immune-stimulatory modalities including radiotherapy or immune checkpoint inhibitors, SIRPant-M works by targeting malignant cells by stimulating cytotoxic T cells and antibodies specific to cancer neoantigens. SIRPant-M also works by reducing immunosuppressive factors and preserving the pro-inflammatory tumor microenvironment.

Through the mobilization of other immune cells and by promoting a multi-prong attack on cancer, the product attacks established tumors and maintains persistent and durable immune memory that resists cancer relapse.

Lymphomas: © immimagery -

Lymphomas: © immimagery -

“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,” said Jelle Kijlstra, MD, MBA, chief medical officer of SIRPant Immunotherapeutics, in a press release.1 “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.”

In May 2023, the FDA cleared the investigational new drug (IND) application for SIRPant-M based on preclinical data, which showed SIRPant-M to demonstrate efficacy across a wide variety of solid tumors and in hematologic tumors.2 Based on these data, the filing of a second IND application for the investigation of the agent in solid tumors, specifically patients with head and neck cancers, is anticipated.

Under the IND, a phase 1 first-in-human trial of SIRPant-M is under assessment for the treatment of patients with relapsed/refractory NHL. A 3+3 design is being utilized in the trial to stagger dose escalations.3

Enrollment in the open-label, phase 1 study is open to patients 18 years and older with histologically or cytologically confirmed NHL. Patients must have received at least 2 lines of systemic therapy, be ineligible or unable to receive other curative therapies, and have recovered from any acute toxic effects associated with prior therapy.3

SIRPant-M is being administered to patients with B-cell NHL and select patients with T-cell NHL alone or in combination with 2.5 Gy of low-dose focal external-beam radiotherapy. Autologous SIRPant-M will be delivered every 2 days through 3 equal intratumoral injections. The 2 dose levels being examined include 90 x 106 cells and 300 x 106 cells.

In the combination cohort of the study, patients are being treated with 2.5 Gy of radiation following each dose of SIRPant-M, for a total of 7.5 Gy radiation.

The primary end points of the trial include safety and tolerability of SIRPant-M alone or in combination with radiation, and the secondary end points are to determine a recommended phase 2 dose of SIRPant-M and objective response rate.

With an estimated study completion date of March 2025, the trial is ongoing at locations in California, New Jersey, and Texas.

“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, chief executive officer of SIRPant, in the press release.1

  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.
  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.
  3. Study of SIRPant-M in participants with relapsed or refractory non-Hodgkin's lymphoma. Updated September 13, 2023. Accessed November 15, 2023.
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