First Patient in US Trial Receives Nexcella’s Light Chain Amyloidosis CAR-T NXC-201

Heather Landau, MD
Credit: MSKCC

Immix Biopharma has dosed the first patient in the phase 1b/2 NEXICART-2 clinical trial (NCT06097832), the first trial in the United States evaluating subsidiary Nexcella's NXC-201 (formerly referred to as HBI0101), an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), for the treatment of relapsed/refractory (r/r) light chain (AL) amyloidosis.¹

The open-label, single-arm, multisite NEXICART-2 study will aim to enroll around 40 participants in total. It will begin by treating 3 patients at a dose of 150x10⁶ CAR+T cells and 3 patients at 450x10⁶ CAR+T cells; pending safety results in these groups, some participants may later receive a dose of 800x10⁶ CAR+T cells. Complete response rate and overall response rate will constitute the primary end points for NEXICART-2. Participants in the study will be required to have adequate cardiac function and to have not previously received a BCMA-targeted therapy. The first patient was dosed at Memorial Sloan Kettering Cancer Center (MSKCC), the trial’s lead site.

“I am excited to initiate the only CAR-T clinical trial currently recruiting for AL Amyloidosis patients that have progressed on front-line daratumumab (Darzalex)-combination therapy,” Heather Landau, MD, the MSKCC Amyloidosis Program director and the NEXICART-2 principal study investigator, said in a statement.¹ “A 1-time therapy such as NXC-201 would provide an attractive option for AL Amyloidosis patients and clinicians. There are no approved drugs for relapsed/refractory AL Amyloidosis today.”

Although this will be the first clinical evaluation of NXC-201 in the United States, the CAR-T is already being assessed in patients with AL amyloidosis and relapsed/refractory (r/r) multiple myeloma (MM) in the ongoing phase 1a/1b NEXICART-1 clinical trial (NCT04720313), which began as a single-center study at the Hadassah University Hospital in Jerusalem, Israel.² Updated results from NEXICART-1 were recently presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD. As of the update, 13 patients with AL amyloidosis have been treated in the trial, at doses of 150x10⁶ (n = 1), 450x10⁶ (n = 2), and 800x10⁶ (n = 10).

The overall hematological response rate was 92% (12 of 13 patients), with 69% of patients (9 of 13) achieving a complete hematological response. It was noted that the 1 patient who did not achieve a response was the only patient to have previously been exposed to an antiBCMA bispecific therapy.³ Furthermore, it was noted that the best responder duration was 28.0 months and ongoing at the time the data were reported.

In terms of safety, 11 of the 13 patients experienced cases of cytokine release syndrome (CRS), with 2 patients (15%) experiencing grade 3 CRS cases and no patients experiencing grade 4 or higher CRS cases.² Notably, none of the 13 patients experienced cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or other neurotoxicity. Grade 3-4 cases of anemia occurred in 3 patients, grade 3-4 cases of thrombocytopenia occurred in 0 patients, grade 3-4 cases of neutropenia occurred in 7 patients, and grade 3-4 cases of lymphopenia occurred in 13 patients.

The ages of the 13 patients ranged from 55 to 82 years (median, 64) and the group included 8 men and 5 women. The patients had received 3 to 10 prior lines of treatment (median, 4). Notably, 12 of the 13 patients (92%) were refractory to their last line of therapy. Two of the 13 patients (15%) had concurrent clinical MM.

“We are excited to present clinical data from the NEXICART-1 clinical study at ASGCT,” Ilya Rachman, MD, PhD, the chief executive officer of Immix Biopharma, said in a May 2024 statement.³ “This study has informed the design of NEXICART-2 clinical trial, expected to open in the US mid2024.”

The investigational new drug (IND) application for NEXICART-2 was cleared by the FDA in November 2023.⁴ The US IND clearance for NXC-201 was preceded by several preliminary steps announced by Nexcella earlier in 2023; these included completion of a preIND meeting with the FDA in June and finishing manufacturing of the first engineering batch for NXC-201 in the US in July.^5,6

REFERENCES
1. Immix Biopharma doses 1st patient in U.S. AL amyloidosis trial with CAR-T NXC-201. News release. Immix Biopharma, Inc. July 8, 2024. Accessed July 11, 2024. https://immixbio.com/immix-biopharma-doses-1st-patient-in-u-s-al-amyloidosis-trial-with-car-t-nxc-201/
2. Assayag M. Academic BCMA-CART cells (HBI0101), a promising approach for the treatment of LC Amyloidosis. Presented at: the ASGCT 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD.
3. Immix Biopharma Announces Positive NXC-201 Relapsed/Refractory AL Amyloidosis Clinical Data in ASGCT 2024 Late Breaking Oral Presentation. News release. Immix Biopharma, Inc. July 8, 2024. Accessed July 11, 2024. https://immixbio.com/immix-biopharma-announces-positive-nxc-201-relapsed-refractory-al-amyloidosis-clinical-data-in-asgct-2024-late-breaking-oral-presentation/
4. Nexcella announces FDA approval of IND application for CAR-T NXC-201, enabling U.S. patient dosing. News release. Nexcella, Inc. November 21, 2023. Accessed July 11, 2024. https://nexcella.com/2023/11/21/nexcella-announces-fda-approval-of-ind-application-for-car-t-nxc-201-enabling-u-s-patient-dosing/
5. Nexcella completes pre-IND meeting with FDA on NXC-201 US clinical trial. News release. Nexcella, Inc. June 26, 2023. Accessed July 11, 2024. https://nexcella.com/2023/06/26/nexcella-completes-pre-ind-meeting-with-fda-on-nxc-201-us-clinical-trial/
6. Nexcella completes initial NXC-201 engineering batch at its U.S. CAR-T manufacturing site. News release. Nexcella, Inc. July 10, 2023. Accessed July 11, 2024. https://nexcella.com/2023/07/10/nexcella-completes-initial-nxc-201-engineering-batch-at-its-u-s-car-t-manufacturing-site/