NXC-201 CAR-T for Amyloidosis

(NEXICART-2 Trial)

Recruiting at 18 trial locations

Overseen By Nexcella

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nexcella Inc.

Must be taking: CD38 monoclonal antibody

Must not be taking: CAR T therapy, BCMA therapy, Steroids

Disqualifiers: Stroke, Seizure, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment, NXC-201 (a CAR-T cell therapy), for people with light chain amyloidosis, a condition where abnormal proteins accumulate in organs like the heart or kidneys. The trial will explore different doses to determine the optimal one. It seeks participants with this condition who have experienced symptoms affecting their heart, kidneys, liver, or nervous system, even after previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires a washout period of at least 4 weeks from any previous investigational treatment and no systemic therapy for AL amyloidosis within 14 days prior to leukapheresis. Additionally, therapeutic doses of steroids are not allowed within 2 weeks prior to leukapheresis.

Is there any evidence suggesting that NXC-201 is likely to be safe for humans?

Research has shown that NXC-201, a type of CAR-T cell therapy, offers promising safety results for people with relapsed or hard-to-treat light chain amyloidosis (AL). In a study involving the first 20 patients, researchers administered NXC-201 safely. Early results suggest that side effects were manageable, which is crucial for treating a challenging condition like AL.

When considering joining a trial, it's important to know that this treatment has been tested in similar patients and was well-tolerated. However, this trial remains in the early stages, so researchers are still determining the best dose and any possible side effects. Always consult a healthcare provider to see if joining a trial is right for you. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NXC-201 CAR-T for amyloidosis because it offers a novel approach by using CAR-T cell therapy, which is not a standard treatment for this condition. Unlike traditional therapies such as chemotherapy and corticosteroids, which aim to manage symptoms, NXC-201 targets amyloid deposits at a cellular level, potentially addressing the root cause of the disease. This cutting-edge method uses genetically engineered T cells to specifically attack and remove harmful protein deposits, offering hope for more effective and long-lasting outcomes. Additionally, CAR-T therapy is known for its ability to provide durable responses in other conditions, which could translate into significant benefits for patients with amyloidosis.

What evidence suggests that NXC-201 might be an effective treatment for amyloidosis?

Research has shown that NXC-201 may help treat relapsed or hard-to-treat light chain amyloidosis (AL). In early studies, the treatment was administered safely and led to quick and significant improvements in patients. For those with multiple myeloma, a type of blood cancer, NXC-201 achieved a high success rate of 92%, suggesting it might also be effective for AL amyloidosis. Early results from the NEXICART-2 trial, which includes a dose escalation phase with different cohorts, support these findings, demonstrating both safety and effectiveness. Overall, these results are promising for individuals considering this treatment. ^{1 2 3 4 6}

Who Is on the Research Team?

Mehrdad Abedi, MD

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory light chain amyloidosis who have had previous treatments. They must not be pregnant, agree to birth control, and have measurable disease. People with inadequate organ function, recent other therapies, certain blood disorders, active infections or second malignancies are excluded.

Inclusion Criteria

I have recovered from previous treatment side effects, except for hair loss and severe nerve pain.

Ability and willingness to adhere to the study visit schedule and all protocol requirements

My cancer can be measured by blood tests.

Exclusion Criteria

Significant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study

I have had treatment for AL amyloidosis before certain medical procedures.

My blood clotting tests are within safe limits, or I'm on stable blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Subjects undergo leukapheresis to provide starting material for NXC-201 CART manufacture

1 day

1 visit (in-person)

Lymphodepletion

Subjects receive Cyclophosphamide and Fludarabine infusions for lymphodepletion

3 days

3 visits (in-person)

Treatment

NXC-201 CART is administered to subjects after lymphodepletion

1 day

1 visit (in-person)

Dose Escalation and Expansion

Subjects receive escalating doses of NXC-201 CAR-positive T cells, guided by safety review committee

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• NXC-201

Trial Overview The study tests NXC-201 CAR-T cells' safety and effectiveness in treating AL amyloidosis that has returned or resisted treatment. It's an early-phase trial where the dose of NXC-201 will be increased gradually to find the right balance between efficacy and safety.

How Is the Trial Designed?

Group I: NXC-201 CAR-T Experimental Treatment 1 Intervention

The dose escalation phase will include the following doses: Cohort 1 - 150×10\^6 CAR-positive (CAR+) T cells (3 patients) Cohort 2 - 450×10\^6 CAR-positive (CAR+) T cells (3 patients) The dose expansion phase will then proceed.

NXC-201 is already approved in United States, European Union for the following indications:

Approved in United States as NXC-201 for:

• None approved yet; under investigation for AL Amyloidosis and Multiple Myeloma

Approved in European Union as NXC-201 for:

• None approved yet; under investigation for AL Amyloidosis and Multiple Myeloma

Who Is Running the Clinical Trial?

Nexcella Inc.

Lead Sponsor

Trials

2

Recruited

200+

Immix Biopharma, Inc.

Industry Sponsor

Trials

2

Recruited

100+

Published Research Related to This Trial

Recent advances in plasma cell-directed therapy for light chain amyloidosis (AL), particularly the combination of daratumumab with bortezomib, cyclophosphamide, and dexamethasone, have shown improved response rates, although the overall death rates remain unchanged, highlighting the need for further improvements in treatment outcomes.

Ongoing research is exploring novel therapies, including B-cell maturation antigen (BCMA) directed therapy and anti-amyloid fibril antibodies, aimed at enhancing survival and reducing early death risks in patients with advanced cardiac complications from AL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis. Kaufman, GP., Cerchione, C.[2023]

Hematopoietic cell transplantation is effective in reversing AL amyloidosis, but patient selection is crucial to maximize benefits and minimize risks, highlighting the importance of identifying specific genetic markers in patients.

Future treatment strategies may involve less invasive methods for stem cell collection and lower doses of chemotherapy, along with improved supportive care, to enhance outcomes for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic cell transplantation for primary systemic amyloidosis: what have we learned. Comenzo, RL.[2019]

Bortezomib-based therapies, specifically bortezomib with dexamethasone (VD) and cyclophosphamide, bortezomib, and dexamethasone (CVD), were well tolerated in 28 patients with light chain amyloidosis (AL), showing a high overall hematological response rate of 93% without any treatment-related mortality.

The CVD regimen led to a quicker response time compared to VD (39 days vs 96 days), and allowed 33% of initially ineligible patients to undergo successful autologous hematopoietic stem cell transplantation, with 88% of those patients maintaining a sustained hematological response 33 months post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib-based induction for transplant ineligible AL amyloidosis and feasibility of later transplantation. Cornell, RF., Zhong, X., Arce-Lara, C., et al.[2018]

In a study of 235 patients with AL amyloidosis who underwent autologous stem cell transplant, the median time to restart chemotherapy was 24.3 months, with 63% showing signs of organ relapse or progression at that time.

Patients with organ progression at the time of therapy resumption had poorer survival outcomes, suggesting that those relapsing from a very good partial response (VGPR) or better may be the best candidates for new treatment trials, as they had a longer time before organ progression occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delineation of the timing of second-line therapy post-autologous stem cell transplant in patients with AL amyloidosis. Hwa, YL., Warsame, R., Gertz, MA., et al.[2021]

Two patients with AL amyloidosis and concurrent multiple myeloma successfully underwent anti-BCMA CAR T cell therapy, demonstrating that careful patient selection and optimization of cardiac and renal function can lead to manageable toxicities.

Both patients achieved a minimal residual disease (MRD)-negative state, suggesting that CAR T therapy can be effective even in those with underlying organ dysfunction, which was previously a concern in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-B Cell Maturation Antigen Chimeric Antigen Receptor T Cell Therapy for the Treatment of AL Amyloidosis and Concurrent Relapsed/Refractory Multiple Myeloma: Preliminary Efficacy and Safety. Das, S., Ailawadhi, S., Sher, T., et al.[2023]

A 71-year-old male with systemic AL kappa amyloidosis and marginal zone lymphoma successfully received third-generation CAR T cell therapy targeting CD19, demonstrating that this approach can be effective for treating AL amyloidosis associated with B-cell malignancies.

The treatment was well tolerated, with only mild early toxicities, and resulted in a significant reduction in IgM and kappa light chains, indicating a deep hematological response six months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First third-generation CAR T cell application targeting CD19 for the treatment of systemic IgM AL amyloidosis with underlying marginal zone lymphoma. Korell, F., Schönland, S., Schmitt, A., et al.[2023]

A novel immunotherapy targeting serum amyloid P (SAP) is being developed to eliminate amyloid deposits in systemic amyloidosis, relying on the drug CPHPC to deplete circulating SAP while preserving some SAP in deposits for targeted treatment.

A mechanistic model has been created to predict the exposure-response relationship for CPHPC in both healthy individuals and patients, taking into account factors like gender and renal function, which will help tailor individualized dosing in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis. Sahota, T., Berges, A., Barton, S., et al.[2018]

In a study of 405 patients with cardiac amyloidosis (CA) over a median follow-up of 33 months, 8.9% required pacemaker implantation, highlighting a notable incidence of this intervention in CA patients.

Key predictors for future pacemaker implantation included a history of atrial fibrillation, prolonged PR interval, and QRS duration greater than 120 ms, which together provided a high negative predictive value for identifying patients at lower risk for needing a pacemaker.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk factors for pacemaker implantation in light-chain and transthyretin cardiac amyloidosis. Porcari, A., Rossi, M., Cappelli, F., et al.[2022]

In a study of 345 patients with light chain amyloidosis (AL) who achieved normal free light chain ratios after treatment, those with elevated involved free light chains (hiFLC) had significantly worse outcomes, including lower progression-free survival (PFS) and overall survival (OS).

Patients with hiFLC after initial therapy showed higher rates of multi-organ involvement and advanced disease stage, indicating that persistent elevation of involved free light chains is a poor prognostic factor, even in patients who initially respond to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL). Tandon, N., Sidana, S., Dispenzieri, A., et al.[2018]

The Cardiac Amyloidosis Registry Study (CARS) has enrolled 1415 patients across 20 centers, focusing on the natural history and treatment patterns of cardiac amyloidosis, with a significant representation of diverse populations, including 25% identifying as Black.

Preliminary results show that 82% of participants have transthyretin (ATTR) cardiac amyloidosis, predominantly the wild-type form, and that the study will provide valuable insights into the condition's progression and treatment efficacy that are not available from traditional clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology. Stern, LK., Grodin, JL., Maurer, MS., et al.[2023]

In a study of 15 patients with cardiac defibrillators undergoing high-dose melphalan followed by autologous stem cell transplantation (HDM/SCT), 93% achieved at least a partial hematologic response, indicating the treatment's efficacy in managing AL amyloidosis.

The study reported a transplant-related mortality of 6.7% and a median overall survival of 40.8 months, with some patients surviving over 10 years, suggesting that HDM/SCT can be a viable option for patients with advanced cardiac amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose melphalan and autologous peripheral blood stem cell transplantation in patients with AL amyloidosis and cardiac defibrillators. Phull, P., Sanchorawala, V., Brauneis, D., et al.[2020]

Citations

1. immixbio.com immixbio.com/immix-biopharmas-nxc-201-nexicart-2-clinical-trial-results-selected-for-oral-presentation-at-ash-2025/

Immix Biopharma's NXC-201 NEXICART-2 Clinical Trial ... “First 20-patient safety and efficacy data from NEXICART-2, the first U.S. trial of CAR-T in R/R light chain (AL) amyloidosis, NXC-201”.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7508

Safety and efficacy data from Nexicart-2, the first US trial of ... In this first reported US CAR-T clinical trial experience in RR AL Amyloidosis, we demonstrate that NXC-201 can be given safely and resulted in rapid and deep ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06971380

Study of HBI0101 (NXC-201) CAR-T Therapy in Multiple ... The goal of the study is to evaluate the efficacy and safety of HBI0101 CART. Detailed Description. Up to 180 subjects with relapsed/refractory (R/R) multiple ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT04720313

NXC-201 (formerly HBI0101) Multiple Myeloma HBI0101 led to an objective response rate (ORR) of 92% in patients with relapsed/refractory multiple myeloma, according to updated data from a phase 1 trial.

5. onclive.com onclive.com/view/dr-raza-on-early-safety-and-efficacy-data-with-nxc-201-in-al-amyloidosis

Dr Raza on Early Safety and Efficacy Data With NXC-201 ... Shahzad Raza, MD, shares preliminary data from the NEXICART-2 trial of NXC-201 in relapsed/refractory light chain amyloidosis.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-02252

Efficacy and Safety of Anti–B-Cell Maturation Antigen ... This largest clinical trial of AL patients treated with anti-BCMA CART demonstrates acceptable and manageable toxicity in a highly frail and resistant ...