FDA Grants Orphan Drug Designation to INB-400/410 in Glioblastoma

The FDA has granted orphan drug designation to the investigational autologous T-cell therapy INB-400 and the allogeneic INB-410 for the treatment of patients with newly diagnosed glioblastoma, according to a press release from IN8bio, Inc.¹

Investigators plan to provide clinical updates on their pipeline programs for INB-400 and INB-410 at future medical meetings throughout the year.

The FDA previously cleared an investigational new drug application for INB-400 in December 2022, permitting investigators to assess the agent in patients with newly diagnosed glioblastoma as part of a phase 2 trial (NCT05664243) that is expected to begin in the second half of 2023.²

Investigators plan to provide clinical updates on their pipeline programs for INB-400 and INB-410 at future medical meetings throughout the year.

“Our novel approach combines engineered, [chemotherapy]-resistant gamma-delta T cells with standard-of-care treatments to amplify immune signals, maximize tumor killing, and eliminate more cancer cells,” William Ho, chief executive officer and co-founder of IN8Bio, said in the press release on the orphan drug designation. “We eagerly anticipate enrolling our first phase 2 patients for INB-400 later this year.”

INB-400 was designed to expand the application of drug resistant immunotherapy (DRI) gamma-delta T cells into other solid tumor types as allogenic or off-the-shelf DeltEx DRI therapy.³

In the multi-center phase 1b/2 study of INB-400, investigators will evaluate genetically modified gamma-delta T cells or DeltEx DRI among an estimated enrollment of 120 patients with newly diagnosed glioblastoma. Prescreening procedures will involve a standard-of-care surgical resection of their tumor to determine eligibility followed by placement of a Rickham catheter to administer chemotherapy into the brain and DRI cells directly to the tumor. In arm A of the trial, investigators will administer T cells to patients on day 1 of each 28-day cycle plus maintenance with temozolomide (Temodar).

The primary end point of the trial is overall survival. Secondary end points include safety and tolerability, overall response rate, time to progression, and progression-free survival.

Patients 18 years and older with histologically or cytologically confirmed history of IDH wild-type glioblastoma are eligible for enrollment on the trial. Additional inclusion criteria include having MRI features consistent with recurrent malignant glioma, a willingness to insert and maintain a Rickham catheter, and a Karnofsky performance status of at least 70%.

Patients who receive cellular immunotherapy or gene therapy within 6 weeks of beginning study treatment or surgical resection or alkylating agent chemotherapy within 4 weeks of beginning study treatment are not eligible for enrollment. Patients are also unsuitable for enrollment if they receive any other investigational agents concurrently while on the study, prior treatment with an allogenic therapy, have a concurrent malignancy or an active second malignancy, or a contraindication to the placement of a Rickham catheter at the time of surgery.

Patients with prior encephalitis, multiple sclerosis, or other central nervous system infections within 1 year prior to glioblastoma diagnosis are also unable to enroll on the trial. Having an uncontrolled intercurrent illness, allergies or hypersensitivity to amino bisphosphonates including zoledronic acid or pamidronic acid, or a history of human immunodeficiency virus or active hepatitis are also grounds for exclusion.

References

1. IN8bio receives FDA orphan drug designation for INB-400/410 for the treatment of newly diagnosed glioblastoma. News release. IN8bio, Inc. April 25, 2023. Accessed May 8, 2023. bit.ly/3M6X6aQ
2. IN8bio announces FDA clearance to initiate a phase 2 clinical trial of INB-400 gamma-delta T cells for glioblastoma. News release. IN8bio, Inc. December 8, 2022. Accessed May 8. 2023. yhoo.it/42igCam
3. Pipeline: our preclinical and clinical programs. In8bio. Inc. Accessed May 8. 2023. bit.ly/44Gr7pc