FDA Grants Orphan Drug Designation to TCB-002 for Relapsed/Refractory AML

The FDA has granted an orphan drug designation to the investigative allogeneic unmodified gamma delta T-cell product, TCB-002, for use as a potential therapeutic option in patients with relapsed/refractory acute myeloid leukemia.

The FDA has granted an orphan drug designation to the investigative allogeneic unmodified gamma delta T-cell product, TCB-002 (OmnImmune), for use as a potential therapeutic option in patients with relapsed/refractory acute myeloid leukemia (AML), according to an announcement from TC Biopharm PLC.1

The decision followed a review of data from a phase 1a/2b trial (NCT03790072), which showed early safety and tolerability with the agent in this patient population.2 Of the 7 patients who received treatment, 3 received the agent at a low dose and 4 received it at a higher dose.

Among those 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 was ultimately lost to follow-up because of comorbidity in the form of bilateral pneumonia that was determined to be unrelated to the study treatment.

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

“This is another milestone achieved by TCBiopharm, further strengthening our leadership position in Gamma Delta therapies for oncology,” Bryan Kobel, chief executive officer of TC Biopharm PLC, stated in a press release. “The granting of orphan drug status provides us a 7-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.”

An allogeneic unmodified cell therapy, TCB-002 is comprised of gamma delta T cells that are sourced from healthy donors, expanded, and activated in large numbers prior to purification; these cells are then formulated for infusion into patients.

The phase 1a/2b trial enrolled patients with a history of AML and relapsed/refractory disease.3 Patients 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.

To be eligible for enrollment, patients needed to be between 18 years of age and 70 years, have more than 5% blasts in the bone marrow or peripheral blood, be candidates for lymphodepleting chemotherapy, a life expectancy of at least 3 months, and have a Karnofsky performance status of 50% or higher. Patients could not be candidates to receive high-dose salvage chemotherapy and/or allogeneic HCT.

If patients had uncontrolled infections, renal insufficiency, heart failure, respiratory insufficiency, significant liver impairment, received treatment with bisphosphonates, or had active autoimmune disease or graft-vs-host disease (GVHD), they were excluded.

On the trial, which set out to enroll 10 participants, patients were given conditioning chemotherapy comprised of fludarabine at 25 mg/m2 from day -6 until day -2, and cyclophosphamide at 500 mg/m2 on days -6 and -5. Patients were dosed with TCB-002 on day 0.

The primary outcome measures of the trial were to assess the incidence of treatment-emergent adverse effects and the incidence of dose-limiting toxicities. The key secondary outcome measures include determining the number of patients achieving a CR, overall survival, and quality of life.

Investigators 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 second patient experienced hematological recovery and had sustained elevation in important immune cells more than 100 days following initial infusion.

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

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

“We look forward to the advancement of OmnImmune in the phase 2b/3 trial and to helping patients in AML in the near future,” Kobel added.


  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/3ttbelP
  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/3tjBGy5
  3. Ex-vivo expanded γδ T-lymphocytes (OmnImmune) in patients with acute myeloid leukameia (AML). ClinicalTrials.gov. Updated March 30, 2021. Accessed March 17, 2022. https://clinicaltrials.gov/ct2/show/NCT03790072