CAR NK Cells for B-Cell Cancers

Not currently recruiting at 5 trial locations

Overseen By Nishi Kothari, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nkarta, Inc.

Must be taking: Anti CD20, BTKi, Venetoclax

Disqualifiers: Burkitt lymphoma, CNS lymphoma, others

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NKX019 (allogeneic CAR NK cells targeting CD19) to determine its safety and tolerability for individuals with certain B-cell cancers, such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, or B-cell acute lymphoblastic leukemia. The treatment uses engineered immune cells to target cancer cells. Suitable candidates have one of these cancers, have tried at least two other treatments, and still have measurable cancer. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that recent use of any cancer-directed therapy within a specified window before the first dose of NKX019 is not allowed. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that NKX019 is likely to be safe for humans?

Research has shown that NKX019, a new treatment using specially engineered immune cells to fight cancer, shows promise in early safety studies. Initial results indicated that patients generally tolerated NKX019 well. Some patients experienced side effects, but these were mostly mild. Notably, 70% of patients treated with NKX019 had a complete response, meaning their cancer was no longer active.

Although still in early testing stages, these results are encouraging for its safety and effectiveness. This therapy remains under study, and further research will provide more information about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-cell cancers, which typically involve chemotherapy, radiation, or monoclonal antibodies like rituximab, NKX019 offers a novel approach by utilizing CAR NK cell therapy. This treatment harnesses the power of natural killer (NK) cells, which are engineered to better recognize and attack cancer cells. Researchers are excited about NKX019 because it has the potential to target cancer cells more precisely, potentially reducing side effects compared to traditional therapies. Moreover, the use of NK cells could provide a faster and more robust immune response, offering new hope for patients with challenging B-cell cancers.

What evidence suggests that NKX019 might be an effective treatment for B-cell cancers?

Research has shown that NKX019, a type of cell therapy, may help treat certain blood cancers such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, and B cell acute lymphoblastic leukemia. Participants in this trial will receive this treatment, which has significantly reduced cancer cells common in these diseases. In one study, patients experienced improvement or even disappearance of cancer symptoms, known as remission. Early results suggest that NKX019 could offer a new option for patients whose previous treatments were unsuccessful. While more research is needed, the initial findings are promising for its effectiveness. ^{1 2 4 5 6}

Who Is on the Research Team?

David Shook, MD

Principal Investigator

Nkarta, Inc.

Are You a Good Fit for This Trial?

Adults with certain B-cell cancers like non-Hodgkin lymphoma, chronic lymphocytic leukemia, or acute lymphoblastic leukemia that have come back or didn't respond to treatment can join. They must have had at least two prior treatments (one for some cases), be in fairly good health, and not pregnant. People with active brain cancer, recent other cancer treatments, or specific types of lymphoma aren't eligible.

Inclusion Criteria

My condition is stable enough to complete at least one treatment cycle.

My condition worsened or didn't improve within 12 months after my last treatment.

My organs are working well.

Exclusion Criteria

I have not had cellular therapy, except for specific approved types.

Pregnant or lactating female

I have Waldenstrom's macroglobulinemia and had plasmapheresis less than 35 days ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fludarabine/cyclophosphamide lymphodepletion followed by 3 weekly doses of NKX019 on Day 0, 7, and 14 of a 28-day cycle

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments up to 2 years after the last dose

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• NKX019

Trial Overview The trial is testing NKX019, a new type of cell therapy using modified natural killer cells aimed at CD19 on cancer cells. It's an early-phase study to see if it's safe and how well patients tolerate it. All participants receive the same experimental treatment without a comparison group.

How Is the Trial Designed?

Group I: NKX019 - CAR NK cell therapy Experimental Treatment 1 Intervention

All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by 3 weekly doses of NKX019 on Day 0, 7, and 14 of a 28-day cycle. Combination cohorts (if opened) will additionally receive rituximab with each cycle.

Who Is Running the Clinical Trial?

Nkarta, Inc.

Lead Sponsor

Trials

4

Recruited

300+

Nkarta Inc.

Lead Sponsor

Trials

2

Recruited

210+

Published Research Related to This Trial

Transfecting CAR-encoding mRNA into primary natural killer (NK) cells is feasible, with optimal CAR expression achieved after 3 days of IL15 stimulation, resulting in over 80% expression and enhanced targeting of CD19+ cancer cells.

Adaptive NK cells, which have specific markers like NKG2C and CD57, showed superior effectiveness in killing CD19+ tumor cells, indicating that the diversity of NK cell subsets is crucial for optimizing CAR-based cancer immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors. Oei, VYS., Siernicka, M., Graczyk-Jarzynka, A., et al.[2019]

Adoptive cell therapy, particularly using CAR T cells, has shown great promise in treating advanced cancers, but the need for patient-specific products limits its widespread use.

Natural killer (NK) cells offer a safer alternative as an allogeneic 'off-the-shelf' therapy, as they do not cause graft-versus-host disease (GVHD) and can be engineered with CARs to enhance their anti-tumor effects, making them a focus for future cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer. Mehta, RS., Rezvani, K.[2019]

The review highlights the growing interest in CAR-engineered NK cells as a promising alternative to CAR-T cells for cancer treatment, with over 200 clinical trials currently underway since the success of Kymriah® and Yescarta® in 2017.

Initial clinical studies of CAR-NK cells targeting both blood cancers and solid tumors show potential, suggesting that these cells could be used as an 'off the shelf' treatment option, making them more accessible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-Expressing Natural Killer Cells for Cancer Retargeting. Kloess, S., Kretschmer, A., Stahl, L., et al.[2020]

A new feeder-free culture method allows for the efficient genetic modification and expansion of peripheral blood-derived NK cells, maintaining their natural responsiveness while enhancing their proliferative capacity.

CAR.CD19-NK cells show significantly improved antileukemic activity against B-cell precursor ALL compared to unmodified NK cells, with similar effectiveness to CAR-T cells but with a lower risk of toxicity in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia. Quintarelli, C., Sivori, S., Caruso, S., et al.[2021]

CAR-engineered NK-92 cells targeting CD19 and CD138 show over 80% CAR expression and high cytotoxicity against leukemia, lymphoma, and multiple myeloma cell lines in vitro, indicating their potential as a safe alternative to CAR-T cells.

A personalized approach using varying ratios of CD19-NK-92 and CD138-NK-92 cells can enhance NK cell effectiveness against leukemia cells, suggesting a tailored treatment strategy based on individual patient antigen profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective Cytotoxicity of Single and Dual Anti-CD19 and Anti-CD138 Chimeric Antigen Receptor-Natural Killer Cells against Hematologic Malignancies. Luanpitpong, S., Poohadsuan, J., Klaihmon, P., et al.[2022]

Engineered NK-92 cells with anti-CD19 chimeric antigen receptors (αCD19-CAR) can effectively kill CD19-positive leukaemic cells that are typically resistant to natural killer cell activity, demonstrating significant cytotoxicity against both leukaemic cell lines and primary patient cells.

The safety of NK-92 cells has been established in phase I clinical studies, and their ability to be expanded under Good Manufacturing Practice (cGMP) conditions makes CAR-modified NK-92 cells a promising treatment option for patients with lymphoid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies. Romanski, A., Uherek, C., Bug, G., et al.[2021]

Chimeric antigen receptor-engineered natural killer (CAR-NK) cells, particularly those derived from cord blood, show promise as a safe and effective immunotherapy for treating CD19-positive hematological malignancies, demonstrating potent cytotoxic activity without the need for HLA matching.

These CAR-NK cells have a strong antileukemia effect and better proliferative capacity, suggesting they could serve as an off-the-shelf allogeneic therapy to address challenging blood cancers, although the long-term durability of their clinical effects remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in chimeric antigen receptor natural killer cell therapy for overcoming intractable hematological malignancies. Tanaka, J.[2021]

A novel dual-effect cord blood natural killer cell (CBNKC) was developed that co-expresses high-affinity PD-1 (HAPD1) and a chimeric antigen receptor (CAR) targeting CD19, showing enhanced anti-tumor effects compared to standard CAR19 CBNKCs.

In both in vitro and in vivo tests, the HAPD1 CAR CBNKCs demonstrated significantly stronger cytotoxicity against CD19-positive tumor cells, indicating their potential as an effective immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Construction and evaluation of dual-effect cord blood natural killer cells expressing highaffinity PD-1 and chimeric antigen CD19 receptor]. Zhong, H., Zou, Q., Liu, H., et al.[2023]

Allogeneic NK cell therapies are promising cancer treatments that can be derived from donor sources, offering off-the-shelf availability and eliminating the risk of graft-versus-host disease (GvHD).

These therapies are currently in various clinical stages, utilizing both non-engineered and engineered NK cells, and show potential in treating both hematological and solid tumors, although regulatory challenges remain for their approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural killer cells in clinical development as non-engineered, engineered, and combination therapies. Lamers-Kok, N., Panella, D., Georgoudaki, AM., et al.[2022]

Citations

1. nature.com nature.com/articles/s41591-023-02785-8

Safety, efficacy and determinants of response of allogeneic ... Autologous anti-CD19 CAR-T cells induce remissions in most patients with B cell malignancies. However, CAR-T cells have limitations including ...

2. mdanderson.org mdanderson.org/newsroom/cd19-targeted-car-nk-cell-therapy-achieves-promising-one-year-results-patients-B-cell-malignancies.h00-159694389.html

CD19-targeted CAR NK cell therapy achieves promising ... CD19-targeted CAR NK cell therapy achieves promising one-year results in patients with B-cell malignancies. Researchers identify key ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05020678

Study Details | NCT05020678 | NKX019, Intravenous ... This is a single arm, open-label, multi-center, Phase 1 study to determine the safety and tolerability of an experimental therapy called NKX019 (allogeneic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428489/

S261: FIRST IN HUMAN DATA OF NKX019, AN ... This Phase 1 study evaluates the safety and preliminary anti-tumor activity of NKX019, an allogeneic NK cell therapy.

5. acrabstracts.org acrabstracts.org/abstract/nkx019-an-allogeneic-off-the-shelf-cd19-targeting-car-nk-cell-therapy-induces-deep-cd19-b-cell-depletion-in-hematological-malignancy-and-models-of-autoimmune-disease/

NKX019, an allogeneic off-the-shelf CD19 targeting CAR ... Translational data from patient samples from the NHL trial demonstrated that NKX019 induces potent and sustained depletion of CD19+ cells from circulation.

6. ir.nkartatx.com ir.nkartatx.com/news-releases/news-release-details/nkarta-announces-updated-clinical-data-anti-cd19-allogeneic-car

Nkarta Announces Updated Clinical Data on Anti-CD19 ... 7 of 10 patients treated with NKX019 monotherapy at 1 billion and 1.5 billion CAR NK cells per dose achieved complete response (70% CR rate)