FDA Grants Fast Track Designation to IVS-3001 in HLA-G+ Clear Cell RCC

It is hypothesized that IVS-3001 may reinvigorate the body’s natural defense to combat cancer more effectively by targeting HLA-G.

The FDA has granted fast track designation to IVS-3001 as a treatment for patients with previously treated HLA-G–positive locally advanced or metastatic clear cell renal cell carcinoma, according to a press release from Invectys, Inc.¹

Supporting data for the designation came from an investigational new drug application that developers originally submitted to the regulatory agency in December 2022, which provided clearance for assessing IVS-3001 as part of a phase 1/2 clinical trial (NCT05672459).²

“We are thrilled to receive the FDA’s fast track designation for IVS-3001,” Jake Kushner, MD, chief executive officer at Invectys, said in the press release. “This recognition further validates the potential of our CAR T-cell therapy in revolutionizing cancer treatment for patients with solid tumors.”

IVS-3001 is designed to target HLA-G, an immune checkpoint and tumor-specific antigen. According to the press release, tumors can use HLA-G to create a protective microenvironment that can evade the immune system and promote tumor growth. It is hypothesized that IVS-3001 may reinvigorate the body’s natural defense to combat cancer more effectively by targeting HLA-G.

Investigators of the proposed phase 1/2 trial are evaluating the pharmacokinetics, safety, tolerability, and efficacy of IVS-3001 in patients with previously treated locally advanced or metastatic solid tumors that are HLA-G positive. Under approved trial protocol, investigators may administer IVS-3001 in up to 24 patients in the phase 1 dose escalation portion and up to 93 in the phase 2a portion.

Intervention in the trial includes a single dose of IVS-3001 CAR T cells, fludarabine phosphate, cyclophosphamide, and leukapheresis all administered intravenously.

The primary end points of the trial are incidence of adverse effects and objective response rate per RECIST v1.1 criteria. Secondary objectives include the pharmacokinetic profile and long-term safety of IVS-3001. Additionally, immune biomarkers related to IVS-3001 and their relationship with clinical response constitute exploratory objectives.

Patients 18 years and older with histologically or pathologically confirmed locally advanced, unresectable, or metastatic select solid tumor malignancy with HLA-G expression on tumor cells as determined by immunohistochemistry analysis are eligible to enroll on the trial. Additional inclusion criteria include having measurable disease per RECIST v1.1 criteria, a life expectancy of more than 12 weeks, an ECOG performance status of 0 or 1, and adequate venous access for apheresis. Patients must also have adequate cardiac, hematologic, hepatic, and renal function to be eligible for enrollment.

Those with primary central nervous system (CNS) tumors or presence of clinically relevant CNS pathology including epilepsy, seizure, paresis, aphasia, or stroke are not able to enroll on the trial. Patients are also unsuitable for enrollment if they previously received a CAR T-cell therapy, had impaired cardiac function or clinically significant cardiac disease, major surgical procedure within 4 weeks prior to study entry, or symptomatic intrinsic lung disease. Having autoimmune disease, chronic infection, or any disease requiring systemic immunosuppressive therapy are also grounds for exclusion from enrollment.

References

1. FDA grants fast track designation to IVS-3001, a CAR-T cell therapy in the treatment of renal cell carcinoma. News release. Invectys, Inc. July 31, 2023. Accessed August 1, 2023. https://shorturl.at/rtQY8
2. Invectys and CTMC announce FDA clearance of IND application for anti-HLA-G CAR-T cell therapy. News release. Invectys, Inc. December 20, 2022. Accessed August 1, 2023. https://shorturl.at/dhoR2