FDA Grants Orphan Drug Designation to NT-I7 for Glioblastoma Multiforme

Orphan drug designation has been granted to NT-I7 by the FDA for patients with glioblastoma multiforme.

The FDA has granted an orphan drug designation (ODD) to NT-I7 (efineptakin alfa; rhIL-7-hyFc; GX-I7), a novel, long-acting human interleukin (IL)-7, for the treatment of patients with glioblastoma multiforme, according to NeoImmunTech.1

NT-I7 is being developed in both oncologic and immunologic indications and the only clinical-stage long-acting human IL-7. IL-7 is a fundamental cytokine used for the development of naïve and memory T cells. Additionally, it works to prolong immune response to chronic or foreign antigens. The agent has been found to have favorable pharmacokinetics, pharmacodynamics, and a promising safety profile which makes it amenable for utilization in combination.

Currently, NT-I7 is being investigated in multiple robust phase 1 and 2 clinical trials in solid tumors and as vaccine adjuvant. The agent is under investigation in the phase 1/2 NIT-107 trial (NCT03687957) evaluating the product in patients with newly diagnosed glioblastoma multiforme. Additionally, the phase 2 NIT-120 trial (NCT05191784) is examining NT-I7 in combination with bevacizumab (Avastin) as a potential therapeutic option for those with recurrent disease.

"We are excited that the FDA granted NT-I7 an ODD in the treatment of glioblastoma multiforme. This decision adds further credibility to our existing clinical evidence that NT-I7 has the potential to bring a new essential therapy option to people with advanced/metastatic glioblastoma multiforme who have undergone prior chemoradiation therapy,” stated Se Hwan Yang, PhD, president and chief executive officer of NeoImmuneTech, in the press release.

In the phase 1 portion of the ongoing NIT-107 trial, patients with newly diagnosed, high-grade gliomas were enrolled to examine the safety of administering NT-17 after chemoradiotherapy to HGG patients and its effect on systemic absolute lymphocyte count.

Enrollment was open to patients with grade 3, 4, or high-risk grade 2 gliomas in need of radiotherapy and temozolomide, acceptable organ and bone marrow function, and a Karnofsky performance status of at least 60. All patients with newly diagnosed high-grade gliomas who had previously completed concurrent radiation therapy and temozolomide were considered eligible.

Participants were treated with concurrent radiotherapy and temozolomide plus adjuvant temozolomide every 4 weeks. Within 1 week following completion, NT-17 was given intramuscularly every 12 weeks, for up to 4 doses.

In the phase 1 portion of the trial, a 3 + 3 design is utilized to identify the maximum tolerated dose of NT-17. Additionally, the double-blinded, placebo-controlled phase 2 study is expected to have 10 patients in each arm.

Primary end points of the phase 1 portion of the NIT-107 trial are safety and tolerability, while in phase 2, the end points consist of the percent increase of absolute lymphocyte count and progression-free survival (PFS).2 Secondary end points include absolute lymphocyte count in phase 1, and immunogenicity both phase 1 and 2.

Preliminary data from the NIT-107 trial showed favorable trends in PFS and overall survival (OS) in patients who received NT-I7 following chemoradiotherapy, according to a presentation given at the 2021 Society for Immunotherapy of Cancer Annual Meeting.3

Phase 1 of the trial was completed with a total of 19 patients, 2 with anaplastic oligodendrogliomas and 17 with glioblastomas. The median age for enrolled patients was 58 years (range 25-78), and participants had a median baseline absolute lymphocyte count of 1000 cells/mm3 before NT-I7 administration, and a median baseline dexamethasone use of 0 mg/day (range 0-12). The median number of NT-I7 doses given was 2 (range: 2-4).4

In regard to safety, treatment-related adverse events (TRAEs) were dose-dependent with the most common TRAEs consisting of grade 1/2 injection site reactions (50%), flu-like symptoms (26%), rash (21%), and fatigue (21%). There were 2 patients who had dose-limiting toxicities at 960 mcg/kgm, and absolute lymphocyte count was increased in a dose-dependent manner with a range of 1.3 – 4.1-fold at week 4 after NT-I7 injection which lasted up to 12 weeks. Data revealed the recommended phase 2 dose of the trial to be 720 mcg/kg.

Overall, these findings revealed the agent to be well tolerated, and to prompt an increase in absolute lymphocyte count. Rapid increases in important cytokines and chemokines were also observed, indicative of immune activation. Phase 2 of the trial is now enrolling patients.

Then in the NIT-120 trial, patients at least 18 years of age, who have histologically diagnosed glioblastoma and have experienced confirmed disease progression following standard therapy with radiotherapy or concurrent chemoradiotherapy and/or adjuvant chemotherapy are currently being enrolled.5 Eligibility is open to patients with a Karnofsky performance status of at least 60, an ECOG performance status of 0 to 2, a life expectancy of more than 12 weeks, an acceptable hematologic and organ function.

Patients enrolled in this trial will be administered 10 mg/kg of bevacizumab intravenously plus NT-I7, which will be administered intramuscularly. The co-primary end points of the trial are PFS and OS, and secondary end points consist of objective response rate, duration of response, disease control rate, safety, and immunogenicity.

Further studies aim to assess NT-17 in hematologic malignancies, additional solid tumors, and other immunology indications.

“We look forward to continuing our collaboration with FDA, as we explore the benefits of NT-I7 in treating people with glioblastoma multiforme in combination with other anticancer treatments, including immunotherapies,” Yang added.

References
  1. FDA grants orphan drug designation (ODD) status to NeoImmuneTech's NT-I7 for the treatment of glioblastoma multiforme. Press release. NeoImmuneTech. July 13, 2022. Accessed July 18, 2022. https://prn.to/3B1VZnI
  2. rhIL-7-hyFc on increasing lymphocyte counts in patients with Newly diagnosed non-severe lymphopenic gliomas following radiation and temzolomide. ClinicalTrials.gov. Updated May 25, 2022. Accessed July 18, 2022. https://clinicaltrials.gov/ct2/show/NCT03687957
  3. Zhou A, Rettig M, Foltz J, et al. NT-I7, a long-acting interleukin-7, promotes expansion of CD8 T cells and NK cells and immune activation in patients with newly diagnosed high-grade gliomas after chemoradiation. J Immunother Cancer. 2021;9:396. doi:10.1136/jitc-2021-SITC2021.396
  4. A phase I/II study to evaluate the safety and efficacy of a novel long-acting interleukin-7, NT-I7, for patients with newly diagnosed high-grade gliomas after chemoradiotherapy: The interim result of the phase I data. J Clin Oncol. 2021;39(15):2040. Doi: 10.1200/JCO.2021.39.15_suppl.2040
  5. GX-I7 in combination with bevacizumab in recurrent glioblastoma (GBM) patients. ClinicalTrials.gov. Updated July 7, 2022. Accessed July 18, 2022. https://clinicaltrials.gov/ct2/show/NCT05191784