CAR NK Cells for B-Cell Cancers

Recruiting in Palo Alto (17 mi)

+5 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Nkarta, Inc.

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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 CAR NK cells targeting CD19) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or B cell acute lymphoblastic leukemia (B-ALL)

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.

What data supports the idea that CAR NK Cells for B-Cell Cancers is an effective treatment?

The available research shows that CAR NK Cells, specifically those targeting CD19, have demonstrated high effectiveness against B-cell cancers. In one study, these cells showed strong activity against cancer cells in laboratory settings, similar to CAR-T cells, but with fewer side effects. Another study highlighted that CAR NK cells could be produced efficiently and used as an 'off-the-shelf' treatment, making them more accessible. These findings suggest that CAR NK Cells are a promising and potentially safer alternative to other treatments like CAR-T cells for B-cell cancers. ^{1 2 3 4 5}

What safety data exists for CAR NK cell treatment for B-cell cancers?

CAR NK cells, including those targeting CD19, have shown a safer clinical profile compared to CAR-T cells, with no risk of graft-versus-host disease. Preclinical studies and early clinical trials indicate that CAR NK cells have potent antileukemic activity with a lower toxicity profile. The safety and efficacy of allogeneic cord blood-derived CD19 CAR-NK cell therapy have been reported, although the durability of clinical effects is still under investigation. Overall, CAR NK cells are considered promising for their safety and effectiveness in treating hematological malignancies. ^{1 4 6 7 8}

Is NKX019 a promising treatment for B-cell cancers?

Yes, NKX019, which uses engineered natural killer (NK) cells to target cancer cells, shows promise as a treatment for B-cell cancers. It can effectively attack cancer cells that are usually resistant to natural killer cells, offering a safer alternative to other therapies without severe side effects. ^{2 3 4 7 9}

Research Team

David Shook, MD

Principal Investigator

Nkarta, Inc.

Eligibility Criteria

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.

Treatment Details

Interventions

• NKX019 (CAR T-cell Therapy)

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.

Participant Groups

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

The Cleveland Clinic Foundation Cleveland, OH

Colorado Blood Cancer Institute Denver, CO

Who Is Running the Clinical Trial?

Nkarta, Inc.

Lead Sponsor

Trials

4

Recruited

300+

Nkarta Inc.

Lead Sponsor

Trials

2

Recruited

210+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. China 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]. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors. [2019]

4. Egypt 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. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Natural killer cells in clinical development as non-engineered, engineered, and combination therapies. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

CAR-Expressing Natural Killer Cells for Cancer Retargeting. [2020]

9. England pubmed.ncbi.nlm.nih.gov

CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies. [2021]