FDA Grants ODD to INB-400 and INB-410 for Newly Diagnosed Glioblastoma

The FDA has granted an orphan drug designation to INB-400 and INB-410, for the treatment of a broad range of malignant glioma, including newly diagnosed glioblastoma multiforme (GBM), according to IN8bio, Inc.¹

This marks the first ever orphan drug designation for genetically modified gamma-delta T-cell therapy, which offers potential incentives such as 7-year market exclusivity for both the INB-400 and INB-410 candidates.

"Our goal is to achieve our Mission of Cancer Zero by eradicating cancer cells and improving patient outcomes," said William Ho, IN8bio chief executive officer and co-founder. "Our novel approach combines engineered, chemo-resistant gamma-delta T cells with standard-of-care treatments to amplify immune signals, maximize tumor killing, and eliminate more cancer cells. We eagerly anticipate enrolling our first phase 2 patients for INB-400 later this year."

Previously in December 2022, the FDA cleared the investigational new drug application (IND) for a phase 2 clinical trial (NCT05664243) in patients with newly diagnosed GBM for the autologous, genetically engineered gamma-delta T-cell therapy, INB-400. Site initiation for the trial is ongoing and patient enrollment is expected to start in the second half of 2023.

Patients aged 18 years and older with histologically or cytologically confirmed IDH wild-type glioblastoma who have a Karnofsky performance status of at least 70% are eligible for enrollment in the study.²

In arm A, patients with newly diagnosed disease will receive INB-400. In phase 1b, patients enrolled in arms B and C must have relapsed and newly diagnosed disease and will be treated with INB-410. Patients enrolled in arm B must not have received more than 1 previous standard treatment for their disease and could not have received prior treatment with bevacizumab (Avastin).

Within the prescreening period of the study, patients will undergo standard resection of their tumor. In arm A, patients will undergo apheresis, which will serve to isolate immune cells from the blood, including the gamma delta T cells needed to make the products. Once the cells are created, they are frozen and stored for use. Then in the phase 1b portion of the trial, a donor will undergo apheresis to provide cells for the product for patients in arms B and C.

Once the cells are successfully collected, patients in arms A and C will be treated with standard treatment for newly diagnosed disease, consisting of temozolomide and radiation for 6 weeks, followed by a 4-week break before the initiation of maintenance treatment, which includes chemotherapy for 5 days given every 28 days for 6 cycles. Then, the cell therapy will be infused on the first day of each 5-day cycle. Patients are expected to receive a total of 6 infusions.

Further, in arm B of the phase 1b portion of the trial, patients will receive 1 dose of temozolomide with the cell therapy every 28 days for 6 cycles. Additionally, patients will be observed for a minimum of 30 days post cell therapy infusion for toxicity.

The primary end point of phase 1b is to establish the recommended phase 2 dose for the phase 2 allogeneic arms and to identify patient or product characteristics that will improve the manufacturing process. The primary end point for arm A in the phase 2 portion is 12-month overall survival (OS) rate, and in arms B and C, it is 9-month OS rate and 12-month OS rate, respectively. Secondary end points are safety, tolerability, overall response rate, time to progression, progression-free survival, and definition of product characteristics.

The company is also conducting 2 investigator-initiated phase 1 clinical trials to evaluate the lead gamma-delta T-cell product candidates INB-200 for patients with newly diagnosed glioblastoma, and INB-100 for the treatment of patients with leukemia undergoing hematopoietic stem-cell transplantation.¹

REFERENCES:

1. IN8bio receives FDA orphan drug designation for INB-400/INB-410 for the treatment of newly diagnosed glioblastoma. News release. IN8bio, Inc. April 25, 2023. Accessed May 8, 2023. https://bit.ly/3HP0BAy

2. A phase 1b/2 drug resistant immunotherapy with activated, gene modified allogeneic or autologous γδ T cells (DeltEx) in combination with maintenance temozolomide in subjects with recurrent or newly diagnosed glioblastoma. ClinicalTrials.gov. Updated December 23, 2022. Accessed May 8, 2023. https://clinicaltrials.gov/ct2/show/NCT05664243