FDA Grants Orphan Drug Status to TCB-002 for Patients With Acute Myeloid Leukemia

The FDA has granted orphan drug status to TCB-002 (OmnImmune) for use as a potential therapeutic option in patients with relapsed/refractory acute myeloid leukemia (AML), according to TC Biopharm PLC.¹

"The granting of orphan drug status provides us a seven-year window post approval of exclusive marketing rights for allogeneic gamma delta use in AML, another added layer of protection around our lead product in a commercial setting beyond our existing strong IP. We look forward to the advancement of OmnImmune in the phase 2b/3 trial and to helping patients with AML in the near future,” stated Bryan Kobel, chief executive officer of TC Biopharm PLC, in the press release.

TCB-002 is made of gamma delta T cells which are sourced from healthy donors, expanded, and activated in large numbers prior to purification. Then, the cells are formulated and used for infusion into patients.

The investigative allogeneic unmodified gamma delta T-cell product received approval following review of data from a phase 1a/2b trial (NCT03790072), which examined the early safety and tolerability with the agent in patients with AML.^2,3

Enrollment was open to patients aged 18-70 years of age with a history of AML and relapsed/refractory disease.3 Other requirements included having more than 5% blasts in the bone marrow or peripheral blood, being a candidate for lymphodepleting chemotherapy, having a life expectancy of at least 3 months, and have had a Karnofsky performance status of 50% or higher. Patients were not eligible for enrollment if they were candidates to receive high-dose salvage chemotherapy and/or allogeneic HCT.

Patients with relapsed/refractory AML could have relapsed after intensive chemotherapy or allogeneic hematopoietic cell transplant (HCT), experienced no response to at least 4 cycles of low-intensity therapy, had disease that was refractory to 2 cycles of induction therapy, or have experienced disease progression on low-intensity therapy with cytarabine, 5-azacitidine, or decitabine.

The target enrollment for the trial was 10 patients and 7 were enrolled. Patients were given conditioning chemotherapy consisting of fludarabine at 25 mg/m2 from day -6 until day -2, and cyclophosphamide at 500 mg/m2on days -6 and -5. On day 0 of treatment, patients were dosed with TCB-002. Of the 7 patients who received treatment, 3 received the agent at a low dose and 4 received it at a higher dose.

Primary outcome measures of the study include assessing the incidence of treatment-emergent adverse effects as well as the incidence of dose-limiting toxicities. Secondary outcome measures included determining the number of patients achieving complete remission (CR), overall survival, and quality of life.

Findings revealed investigators to have examined allogeneic gamma delta T-cell persistence in 2 patients who received treatment with TCB-002. In 1 of these patients who received 3 infusions, the product continued to be detectable after 100 days. The other patient experienced hematological recovery and had sustained elevation in important immune cells more than 100 days following initial infusion.

In the 4 patients who received TCB-002 at a higher dose level, 50% achieved CRs with 1 patient observed to have a significant reduction in cancer blast count at day 14 and 1 patient having experienced disease progression.

Of the participants who received the lower dose, 1 patient achieved a morphologic leukemia-free state (MLFS), 1 had stable disease described as a near-complete response (CR), and 1 met all safety end points but left prior to follow-up due to comorbidity in the form of bilateral pneumonia that was determined to be unrelated to the study treatment.

Additionally, 2 patients who achieved a CR and stable disease were re-dosed with TCB-002. The patient with MLFS went on to receive 2 additional infusions of the agent. Notably, no adverse effects were observed following these infusions.

TCB-002 was found to be safe and tolerable, with no toxicity concerns raised during meetings held by the Safety Review Committee. No patients who received TCB-002 experienced GVHD, immune effector cell–associated neurotoxicity syndrome, or cytokine release syndrome.

References:

1. TC BioPharm announces FDA orphan drug status granted for OmnImmune. News release. TC BioPharm PLC; March 17, 2022. Accessed March 17, 2022. https://prn.to/3LcR0mn

2. TC BioPharm announces positive phase 1b/2a data in late-stage acute myeloid leukemia patients treated with allogeneic gamma delta T cells. News release. TC Biopharm PLC; March 8, 2022. Accessed March 17, 2022.https://prn.to/3wjkAlN

3. Ex-vivo expanded γδ T-lymphocytes (OmnImmune) in patients with acute myeloid leukemia (AML). ClinicalTrials.gov. Updated March 30, 2021. Accessed March 17, 2022. https://clinicaltrials.gov/ct2/show/NCT03790072