FDA Issues Clinical Hold on MELANI-01 Trial With UCARTCS1A in Myeloma

The FDA has issued a clinical hold on the phase 1 MELANI-01 trial evaluating the CAR T-cell product UCARTCS1A in the treatment of patient with relapsed/refractory multiple myeloma, according to Cellectis, the manufacturer of the product.¹

The clinical hold was implemented following the submission of a safety report on 1 patient with relapsed/refractory disease who was enrolled on the trial at dose level 2. The patient, who had received prior treatment with several lines of therapy, including autologous CAR T cells, experienced a fatal cardiac arrest, which was found to be a treatment-emergent adverse event. The case continues to undergo clinical assessment, with additional information being collected on both the immediate and underlying causes of this event.

Prior to the hold, the biopharmaceutical company had expanded enrollment at dose level 1. That dose, according to Cellectis, could potentially be the appropriate dose for further examination in the expansion portion of the trial as well as the recommended dose for the phase 2 portion of the trial, based on an examination of preliminary clinical and translational findings.

“We share the FDA’s commitment to patient safety and are working collaboratively with the agency and the investigators to resolve this clinical hold,” Carrie Brownstein, MD, chief medical officer of Cellectis, stated in a press release. “The safety of patients enrolled in our clinical trials is our utmost priority and we at Cellectis remain committed to safety resuming the clinical development of UCART product candidate targeting CS1 for patients with multiple myeloma and unmet medical need.”

In January 2019, the FDA approved the biopharmaceutical company’s investigational new drug application to launch the MELANI-01 trial for UCARTCS1A is an allogeneic, off-the-shelf, gene-edited T-cell product that was developed to target CS1/SLAMF7-expressing hematologic malignancies.² In the open-label, dose-escalation, phase 1 trial, investigators are examining the safety and efficacy of 1 infusion of the CS1-targeted CAR T-cell product UCARTCS1A in patients with relapsed/refractory multiple myeloma, and seek to identify the maximum tolerated dose.³

The primary end point of the trial is safety: to examine the incidence, nature, and severity of adverse events (AEs) and serious AEs with the product throughout the study. In order to be eligible for enrollment, patients must have had a confirmed diagnosis of active multiple myeloma and have relapsed on prior treatment. Participants must also have had an ECOG performance status of 0 or 1, adequate organ function, and have not received prior treatment with investigational gene therapy targeting CS1 or CS1-targeted CAR T-cell therapy.

The trial had commenced dosing under the leadership of Krina K. Patel, MD, MSc, principal investigator, study coordinating investigator, and assistant professor in the Department of Lymphoma/Myeloma of the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center. The trial is also being conducted at Hackensack Meridian under the direction of David Siegel, MD, director of the Multiple Myeloma Institute at John Theurer Cancer Center. Another site opened at Weill Cornell Medicine under the supervision of Adriana Rossi, MD, associate clinical director of the Myeloma Center and assistant professor of medicine in the Division of Hematology and Medical Oncology.

Now, the biopharmaceutical company is working with the FDA to address the regulatory agency’s requests. To this end, they are implementing changes to the trial protocol to improve patient safety. Cellectis expects to submit the information requested by the FDA, including an amended protocol, in the near future.

Other CAR T-cell products, UCART123 and UCART22, are under evaluation in the AMELI-01 trial in relapsed/refractory acute myeloid leukemia and the BALLI-01 trial in relapsed/refractory B-cell acute lymphoblastic leukemia, respectively.

References

1. Cellectis reports clinical hold placed on MELANI-01 study. News release. Cellectis. July 6, 2020. Accessed July 6, 2020. bit.ly/3f5Ov5C.
2. Universal chimeric antigen receptors. Cellectis. Accessed July 6, 2020. bit.ly/3gD3Evg.
3. Study evaluating safety and efficacy of UCART targeting CS1 in patients with relapsed/refractory multiple myeloma (MELANI-01). ClinicalTrials.gov. Updated March 3, 2020. Accessed July 6, 2020. https://clinicaltrials.gov/ct2/show/NCT04142619.