Multiple Myeloma Therapy GC012F Safe, Effective in New Cases

GC012F, Gracell Biotechnologies’ investigational dual FastCAR T-cell therapy, was safe and highly effective at eradicating cancer cells in people with high-risk, newly diagnosed multiple myeloma, according to preliminary findings from an ongoing Phase 1 trial.

“We are thrilled to report that BCMA/CD19 dual targeting FasTCAR-T GC012F is showing a very favorable safety profile and encouraging efficacy in newly-diagnosed multiple myeloma patients,” said Wendy Li, MD, chief medical officer at Gracell, in a company press release.

The trial’s early results will be presented in an oral presentation at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, Dec. 10­–13, in New Orleans.

The presentation will be titled “Phase I open-label single-arm study of BCMA/CD10 dual-targeting FasTCAR-T-cells (GC012F) as first-line therapy for transplant-eligible newly diagnosed high-risk multiple myeloma.”

“We are excited to present the first clinical data evaluating GC012F as a first-line therapy for multiple myeloma at ASH 2022, a premier gathering of leading minds in hematology and oncology from around the world,” Li said.

High-risk, newly diagnosed multiple myeloma patients have “poor outcomes with standard first-line therapy,” the researchers wrote, even among those who are eligible for standard autologous hematopoietic stem cell transplant.

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A new immunotherapy

A CAR T-cell therapy — a new immunotherapy that uses the body’s immune system to eliminate cancer cells —  “with high efficacy and manageable safety profile would be a potential solution to this significant unmet need,” they wrote.

The approach involves collecting immune cells called T-cells from a patient and genetically engineering them to produce a receptor protein called chimeric antigen receptor (CAR) that helps recognize and eliminate cancer cells. The engineered cells are then infused back into the patient.

In GC012F, CAR T-cells target two proteins simultaneously: B-cell maturation antigen (BCMA) and CD19. BCMA is found at high levels on the surface of myeloma cells and the CD19 protein is present on the surface of early progenitor B-cells that could give rise to more myeloma cells.

With this dual-target mechanism, the therapy is expected to “drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma,” according to Gracell.

GC012F was created with Gracell’s proprietary FasTCAR platform, shortening the manufacturing process of CAR T-cell therapies to 22–36 hours from the standard one to six weeks.

It received orphan drug status in the U.S. for multiple myeloma last year. The status is designed to accelerate GC012F’s clinical development and regulatory review by providing regulatory support and financial benefits, along with a seven-year marketing exclusivity period upon approval, if granted.

In a previous Phase 1 trial (NCT04236011), GC012F was shown to safely and effectively result in deep and durable responses in people with relapsed or refractory multiple myeloma.

These promising results prompted the launch of an investigator-initiated Phase 1 trial (NCT04935580) to test its safety and effectiveness in up to 20 transplant-eligible, newly diagnosed multiple myeloma patients with high-risk features. Recruitment of patients, ages 18–70, may still be ongoing at a single site in China.

Results of GC012F immunotherapy

At a data cutoff date of July 25, 13 participants had received a single infusion of GC012F at one of three doses: 100,000, 200,000, or 300,000 cells per kilogram of body weight. The CAR T-cell therapy was administered following chemotherapy regimens to eliminate myeloma cells and make room for the genetically engineered T-cells.

Patients’ median age was 59 (range, 43–65) and they had been diagnosed at a median of 4.5 months before treatment (range, 3.2–5.4). They were followed for a median of 5.3 months (range, 2.3–12.5) after GC012F treatment.

All 13 patients achieved robust CAR-T cell expansion and achieved very good partial responses or better, reflecting an overall response rate (ORR) of 100%. Also, 69% of them attained stringent complete responses. Complete responses refer to total cancer eradication, while partial responses refer to partial elimination. Very good partial responses and stringent complete responses are stronger types of partial and complete responses, respectively.

All patients also achieved minimal residual disease (MRD) negativity, defined as having less than one cancer cell among 10,000 white blood cells. Patients with available data at both one month and six months after treatment were MRD negative at both time points.

Also, all patients receiving the middle GC012F dose and half of those given the highest dose achieved MRD negative-stringent complete response. This may be due to the fact that patients in the middle-dose group carried fewer high-risk factors than those in the high-dose group, the researchers noted.

“Patients continue to be followed for deepening responses,” the researchers wrote.

The therapy was generally well tolerated. Mild to moderate cytokine release syndrome (CRS), a severe complication of immunotherapy that causes immune system overactivation, occurred in three patients (23%).

There were no reports of severe or life-threatening treatment-related CRS and no immune effector cell-associated neurotoxicity syndrome, where neurotoxicity is driven by an inflammatory immune response that commonly occurs with CAR-T cell therapy.

“In this phase [1] study for transplant-eligible newly diagnosed high-risk [multiple myeloma], BCMA-CD19 dual FasTCAR-T GC012F showed a very favorable safety profile, high efficacy with 100% ORR and 100% MRD negativity,” the researchers wrote. “The promising preliminary results warrants further assessment of GC012F for [transplant-eligible newly diagnosed multiple myeloma], with more patients and longer follow-up.”

“We believe the data further validates our proprietary FasTCAR next-day manufacturing platform and the potential of GC012F in treatment for multiple myeloma,” Li said, calling the treatment of newly diagnosed patients “a new frontier for CAR-T.”

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