Gamma-Delta T-cell Therapy Gets Green Light From FDA for Phase 2 Trial

IN8bio’s INB-400, an investigational, genetically modified gamma-delta T-cell therapy intended to treat glioblastoma (GBM), has received clearance of its investigational new drug (IND) application by the FDA.¹

INB-400 is based on the company’s DeltEx platform and consists of drug-resistant immunotherapy (DRI) cells, which are cells that have been modified to be able to resist damage from concurrently administered chemotherapy treatments.^1,2 IN8bio intends to initiate a multicenter phase 2 clinical trial for INB-400 in 2023, which will evaluate safety and efficacy. The study, in line with FDA guidelines announced in November 2022, will evaluate both an autologous and an allogeneic form of the cell product.³ The trial’s initial arm will evaluate autologous INB-400 in patients with newly diagnosed GBM.¹ Later expansion of the trial will include the evaluation of allogeneic cells in patients with relapsed/refractory GBM. It may also include evaluation of the allogeneic product as a first-line treatment. The study’s primary end point is overall survival, and secondary end points include tolerability, progression-free survival, overall response rate, and time to progression. It will take place at several locations in the United States.

“Obtaining clearance to begin the INB-400 phase 2 clinical trial is an important milestone for IN8bio as it is our first company-sponsored IND,” William Ho, chief executive officer and co-founder, IN8bio, said in a statement regarding the news.¹ “This milestone demonstrates the clinical, regulatory, and CMC capabilities of the IN8bio team in continuing to advance novel gamma-delta T-cell therapies to cancer patients. The clinical program is designed to eventually assess DeltEx DRI with both autologous and allogeneic approaches in both the front-line and relapsed setting. We believe the insights we unlock in GBM will be essential as we apply our DeltEx platform across multiple solid tumor cancers.”

In September of this year, IN8Bio announced that the University of Louisville (UofL) Health - Brown Cancer Center GMP Manufacturing Facility will serve as its manufacturing partner for INB-400.⁴ The facility housed within the center, referred to as the Dunbar CAR T-Cell Program, was launched in 2019 with a $1 million pledge from Louisville resident Thomas E. Dunbar.

“We are proud to be partnering with the UofL, the UofL Health - Brown Cancer Center, and the Dunbar CAR T-Cell Program who have been at the forefront of clinical development and patient access to novel cellular immunotherapies,” Kate Rochlin, PhD, chief operating officer, IN8bio, said in a statement at the time of the announcement.⁴ “One of the biggest challenges facing cell therapy companies is efficient access to high-quality manufacturing facilities with the experience and capacity required to support multicenter clinical trials and commercial manufacturing. The Dunbar CAR T-Cell Program has a superb facility designed specifically to advance the development of promising T-cell therapies.”

IN8bio has several other cell therapy programs currently in development. INB-100, an investigational allogeneic gamma-delta T-cell therapy, is currently being evaluated in a phase 1 clinical trial (NCT03533816) for patients with acute myeloid leukemia undergoing haploidentical hematopoietic stem cell transplant.⁵ Early efficacy data from the trial was covered in July of this year by CGTLive, and IN8Bio expects to present updated data at the American Society of Hematology (ASH) on Monday, December 12th.¹ Another gamma-delta T-cell product, INB-200, is currently being evaluated in a phase 1 clinical trial for patients with newly diagnosed GBM (NCT04165941). The company’s other programs remain in preclinical development.

REFERENCES

1. 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. https://investors.in8bio.com/news-releases/news-release-details/in8bio-announces-fda-clearance-initiate-phase-2-clinical-trial 

2. Our technology. IN8Bio website. Accessed December 8, 2022. https://in8bio.com/technology/

3. Studying multiple versions of a cellular or gene therapy product in an early-phase clinical trial. Website. FDA. Accessed December 8, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/studying-multiple-versions-cellular-or-gene-therapy-product-early-phase-clinical-trial 

4. IN8bio partners with the Dunbar CAR T-cell program at the University of Louisville as the manufacturing center for INB-400. News release. IN8bio, Inc. September 15, 2022. https://investors.in8bio.com/news-releases/news-release-details/in8bio-partners-dunbar-car-t-cell-program-university-louisville 

5. IN8bio observes durable morphologic complete responses in ongoing phase 1 clinical trial of INB-100, an allogeneic gamma-delta T cell therapy in high-risk leukemia patients. News release. IN8bio, Inc. July 27, 2022. https://investors.in8bio.com/news-releases/news-release-details/in8bio-observes-durable-morphologic-complete-responses-ongoing