Heather Landau, MD, on Evaluating CAR-T NXC-201 for Light Chain Amyloidosis

Heather Landau, MD
Credit: MSKCC

Immix Biopharma and its subsidiary Nexcella are currently conducting a phase 1b/2 clinical trial (NCT06097832; NEXICART-2) in the United States aimed at evaluating NXC-201, an investigational autologous BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy, for the treatment of relapsed/refractory (r/r) light chain (AL) amyloidosis. Early results from this study were recently presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 30 to June 3, in Chicago, Illinois, by principal NEXICART-2 investigator Heather Landau, MD, the Memorial Sloan Kettering Cancer Center Amyloidosis Program director.

In an interview with CGTLive®, Landau went over the key results presented at the conference and their implications. She also briefly discussed future plans for NXC-201 and pointed out that the trial is actively recruiting at 7 sites in the US.

CGTLive: Can you give some background context about your presentation?

Heather Landau, MD: AL amyloidosis is a plasma cell disorder that causes morbidity and mortality when pathologic plasma cells produce amyloidogenic light chains that deposit in critical organs, especially the heart. It is about 1/5 as common as multiple myeloma (MM) and at times goes unrecognized based on patients’ nonspecific symptoms that mimic more common conditions. Yet, without treatment patients develop progressive organ disease that can lead to death. It has been a challenge to study drugs in AL amyloidosis because pharmaceutical companies have been reluctant to conduct trials in a disease that is rare and where patients have a risk of sudden death. However, when we effectively eliminate the pathologic plasma cells and reduce circulating light chains, patients have tremendous benefit. In 2021 daratumumab was the first and remains the only FDA-approved drug for this condition based on data from the Andromeda study showing 60% of patients who receive daratumumab in the upfront setting can achieve a hematologic complete response. Unfortunately, if patients don’t achieve deep responses or relapse following daratumumab there are limited options to treat these patients due to poor efficacy and significant toxicity. No drug has been FDA approved for r/r patients.

Yet, based on the rapid and deep responses that we have seen with BCMA directed CAR T-cells in MM, we were motivated to study this strategy. NXC-201 is a unique CAR T-cell that was studied in a trial designed for MM patients but patients with AL amyloidosis were allowed to receive the treatment. At the time we designed the trial 4 patients with AL amyloidosis had received this drug and had been reported with a favorable safety and efficacy profile. Therefore we initiated the first phase 1/2 clinical trial of CAR T-cells specifically for r/r amyloidosis patients.

What are some of the key data points you presented at ASCO this year?

We treated 10 patients in the dose escalation portion (3 at 150x10⁶ and 7 at 450x10⁶) with no dose-limiting toxicities observed and have opened the dose expansion arm. Another 5 patients have been treated at 450x10⁶. In the ASCO presentation we reported the first 10 patients on the dose escalation phase and found the treatment to be safe (mild and manageable cytokine release syndrome and no neurotoxicity of any kind) and effective with all patients experiencing rapid and deep hematologic remissions with a median time to first response of 7 days. 70% achieved complete hematologic responses. Although 3 others have not yet met that benchmark because their serum immunofixation remains positive. However, they are all minimal residual disease negative in the bone marrow (at Day+25) and expected to evolve into deeper remissions (ie become immunofixation electrophoresis negative).

How would you summarize the big-picture implications that doctors and the broader healthcare community should take away from this new data?

This is the first CAR T-cell trial for patients with r/r AL amyloidosis – a condition that has a serious unmet medical need since they have no FDA approved treatment options.

This therapy is safe and exquisitely effective resulting in deep hematologic remissions and even organ responses despite short follow-up.

What are the next steps for this research? Are there any challenges that still need to be addressed? 

We need to study the long-term safety of this approach and evaluate the durability of the responses. However we know from the stem cell transplant literature that deep remission can often be very, very durable in this disease.

Is there anything not covered by the previous questions that you want to share? 

This multicenter trial is open in 7 sites across the US. Please consider this trial for any patient with a suboptimal response to dara-VCd or those who relapse after daratumumab based therapy.

This transcript has been edited for clarity.

Click here to view more coverage of ASCO's 2025 Meeting.

REFERENCE
1. Landau H. Safety and efficacy data from Nexicart-2, the first US trial of CAR-T in R/R light chain (AL) amyloidosis, NXC-201. Presented at the 2025 ASCO Annual Meeting, held May 30 to June 3, in Chicago, Illinois. Abstract #7508