M-CENK for Advanced or Metastatic Cancer

Recruiting at 1 trial location

Overseen By Jayson Garmizo

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ImmunityBio, Inc.

Must not be taking: Antibiotics, Corticosteroids

Disqualifiers: Organ transplant, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 12 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a two-part, open-label phase 1 study to evaluate safety and preliminary efficacy of M-CENK Suspension for Infusion, Cryopreserved, and N-803 for subcutaneous administration in subjects with locally advanced or metastatic solid tumors. The study consists of two cohorts: cohort 1 includes subjects with either newly diagnosed solid tumors who have not received prior therapy or subjects who have received prior first line treatment; and cohort 2 that includes subjects with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies. The two cohorts will be conducted simultaneously.

Will I have to stop taking my current medications?

The trial requires a 'washout period' (time without taking certain medications) before starting M-CENK. Specifically, you must stop approved chemotherapy and immunotherapy 14 days before, and investigational chemotherapy 30 days before. The protocol does not specify other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the treatment M-CENK for Advanced or Metastatic Cancer?

Research shows that IL-15 superagonists, like N-803 used in M-CENK therapy, can activate immune cells such as natural killer (NK) cells and CD8+ T cells, which are important for fighting cancer. These superagonists have demonstrated the ability to shrink tumors in animal studies and are being tested in clinical trials for cancer patients. ^{1 2 3 4 5}

Is M-CENK treatment generally safe for humans?

The treatment, involving IL-15 superagonist (also known as N-803), has been tested in healthy volunteers and cancer patients, showing no serious adverse events. Common mild side effects included injection site reactions, chills, and fever, but overall, it was well tolerated and boosted immune cell activity. ^{1 6 7 8 9}

What makes the M-CENK treatment unique for advanced or metastatic cancer?

M-CENK treatment is unique because it combines M-CENK cells, which are a type of immune cell therapy, with N803, an IL-15 superagonist that boosts the immune system's ability to fight cancer. This combination aims to enhance the body's natural defenses against cancer cells, offering a novel approach compared to traditional treatments. ^{10 11 12 13 14}

Research Team

Leonard Sender, MD

Principal Investigator

ImmunityBio, Inc.

Eligibility Criteria

Adults with advanced solid tumors that can't be surgically removed or have spread, who've had prior treatments (or none for newly diagnosed), and are able to follow the study plan. They must have measurable disease, adequate organ function, no serious illnesses or autoimmune diseases, not on certain medications like high-dose steroids, and agree to use contraception.

Inclusion Criteria

My brain cancer has not worsened after surgery or radiation.

My cancer has a genetic mutation and has worsened despite targeted therapy.

My cancer is advanced, cannot be surgically removed, or has spread.

Exclusion Criteria

Known hypersensitivity to any component of the study medication(s)

I am being treated for a systemic autoimmune disease like lupus or rheumatoid arthritis.

My blood tests show I might not be healthy enough for this trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis

Collection of mononuclear cells (MNCs) from participants for manufacturing M-CENK cells

1 week

1 visit (in-person)

Treatment

Participants receive M-CENK and N-803 treatments. M-CENK may be administered up to 10 times weekly, and N-803 up to 5 doses every 2 weeks.

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Apheresis collection of lymphocytes
• M-CENK
• N803

Trial Overview The trial is testing a new therapy called M-CENK with N803 in two groups: one with patients new to treatment or after first-line therapy; another with those whose cancer returned after at least two treatments. It's an early-phase study checking safety and initial results of these drugs.

Participant Groups

Group I: Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors Experimental Treatment 2 Interventions

Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies or not a candidate for therapy of proven efficacy for their disease.

Group II: Cohort 1: Subjects newly diagnosed no prior therapy or prior first line treatment Experimental Treatment 1 Intervention

Cohort 1: Subjects with either newly diagnosed solid tumors who have not received prior therapy or subjects who have received prior first line treatment. Cohort 1 may subsequently enroll in cohort 2 part B if they have progressive disease after ≥ 2 prior therapies or if they have progressive disease within 12 months of receiving neoadjuvant or adjuvant chemotherapy and meet the inclusion criteria for cohort 2 part B.

Who Is Running the Clinical Trial?

ImmunityBio, Inc.

Lead Sponsor

Trials

75

Recruited

5,000+

Richard Adcock

ImmunityBio, Inc.

Chief Executive Officer since 2024

Information not available

Dr. Patrick Soon-Shiong

ImmunityBio, Inc.

Chief Medical Officer since 2021

MD

Findings from Research

IL-15 superagonists, created by combining IL-15 with its receptor, show enhanced efficacy in stimulating natural killer (NK) and CD8+ T cells, which are crucial for fighting cancer, and have demonstrated tumor regression in animal studies.

Currently, there are fourteen ongoing phase I/II clinical trials investigating the safety and efficacy of IL-15 superagonists in cancer patients, with results on toxicity and effectiveness eagerly anticipated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunobiology of the IL-15/IL-15Rα complex as an antitumor and antiviral agent. Guo, Y., Luan, L., Patil, NK., et al.[2018]

ALT-803, an interleukin-15 superagonist, effectively stimulates memory CD8+ T cells to proliferate and enhance their immune functions without needing specific antigens.

This treatment not only boosts the number of memory CD8+ T cells but also transforms them into powerful innate immune effector cells capable of attacking cancer cells, demonstrating significant potential for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The IL-15-based superagonist ALT-803 promotes the antigen-independent conversion of memory CD8+ T cells into innate-like effector cells with antitumor activity. Wong, HC., Jeng, EK., Rhode, PR.[2022]

The developed hydrogel microspheres (MS~IL-15) provide a long-acting form of IL-15, maintaining a half-life of about 168 hours initially, which allows for prolonged immune cell expansion in mice for up to 4 weeks after a single injection.

When used in combination with other immuno-oncology agents, MS~IL-15 significantly enhances survival and antitumor activity in mouse models of prostate cancer and adult T-cell leukemia, demonstrating its potential as an effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A very long-acting IL-15: implications for the immunotherapy of cancer. Hangasky, JA., Chen, W., Dubois, SP., et al.[2022]

Interleukin-15 (IL-15) is a promising cytokine in cancer immunotherapy that enhances the immune response by activating natural killer (NK) cells, natural killer T (NKT) cells, and memory CD8+ T cells, potentially leading to the destruction of cancer cells in the tumor microenvironment.

IL-15-based therapies, including CAR T and CAR NK cell treatments, show encouraging results in preclinical and early clinical trials, suggesting that they could be effectively combined with other therapies like checkpoint inhibitors for improved cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological effects of IL-15 on immune cells and its potential for the treatment of cancer. Zhang, S., Zhao, J., Bai, X., et al.[2021]

The novel IL-15 superagonist F4RLI significantly enhances the half-life and stability of IL-15, extending its exposure in mice by approximately 28- and 200-fold compared to the standard IL-15 monomer, which could improve its effectiveness in cancer treatment.

F4RLI not only stimulates the proliferation of key immune cells like CD8+ T cells and NK cells but also shows promising synergistic effects when combined with immune checkpoint inhibitors and angiogenesis inhibitors, leading to significant tumor growth suppression in mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A homodimeric IL-15 superagonist F4RLI with easy preparation, improved half-life, and potent antitumor activities. Lv, L., Wang, H., Shi, W., et al.[2022]

N-803, a chimeric IL-15 superagonist, has a significantly longer half-life (approximately 20 hours) compared to regular IL-15, which enhances its potential as an immunotherapy for cancer.

The phase 1 study demonstrated that N-803 is safe and well-tolerated in healthy volunteers, with no serious adverse events reported, and it effectively increased levels of immune cells like NK cells and CD8+ T cells, suggesting it could boost antitumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial Characterizing the Pharmacokinetic Profile of N-803, a Chimeric IL-15 Superagonist, in Healthy Volunteers. Rubinstein, MP., Williams, C., Mart, C., et al.[2023]

Recombinant human IL-15 (rhIL-15) was safely administered to patients with metastatic melanoma and renal cell cancer, with a maximum-tolerated dose established at 0.3 μg/kg per day due to dose-limiting toxicities like hypotension and thrombocytopenia.

IL-15 treatment led to significant changes in immune cell populations, including a tenfold increase in NK cells and indications of tumor activity, such as the clearance of lung lesions in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. Conlon, KC., Lugli, E., Welles, HC., et al.[2022]

In a phase I trial involving 27 cancer patients, continuous intravenous infusion of rhIL15 for 10 days was found to have a maximum tolerated dose (MTD) of 2 μg/kg/day, but it was associated with serious adverse events, including two deaths likely related to the treatment.

Despite the toxicity, the treatment led to significant increases in immune cells, such as a 5.8-fold increase in CD8+ T cells and a 38-fold increase in NK cells, suggesting potential antitumor activity and supporting further research combining IL15 with other cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL15 by Continuous Intravenous Infusion to Adult Patients with Solid Tumors in a Phase I Trial Induced Dramatic NK-Cell Subset Expansion. Conlon, KC., Potter, EL., Pittaluga, S., et al.[2021]

In a phase I study involving 11 patients with metastatic cancers, a 5-day continuous intravenous infusion of recombinant human interleukin-15 (rhIL-15) at a dose of 4 µg/kg/day was found to significantly expand natural killer (NK) cells and CD8+ T cells without dose-limiting toxicities, making it a promising treatment option.

The treatment enhanced the cytotoxic functions of NK cells, which could improve the effectiveness of tumor-targeting monoclonal antibodies that rely on antibody-dependent cellular cytotoxicity (ADCC), suggesting a potential synergistic therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course IL-15 given as a continuous infusion led to a massive expansion of effective NK cells: implications for combination therapy with antitumor antibodies. Dubois, SP., Miljkovic, MD., Fleisher, TA., et al.[2023]

Cytokine-induced killer (CIK) cell therapy was administered to 16 patients with metastatic renal cell carcinoma (mRCC), showing minimal toxicity and no immediate adverse reactions, indicating a safe treatment option.

The therapy resulted in significant immunological responses, with 3 patients achieving complete response and 1 patient achieving partial response, suggesting that CIK cell immunotherapy is effective in enhancing the immune function against mRCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with cytokine-induced killer cells in metastatic renal cell carcinoma. Su, X., Zhang, L., Jin, L., et al.[2010]

Cytokine induced autologous killer (CIK) cell infusion is a safe and effective immune therapy for elderly patients with hematological malignancies, with no adverse reactions reported during the treatment of 20 patients.

The treatment led to significant improvements in immune function, quality of life, and remission rates, with 11 patients achieving complete remission and 7 achieving partial remission after multiple cycles of CIK cell infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of immune function test to evaluate effect of cytokine-induced autologous killer cell infusion for elderly patients with hematological malignancies]. Cai, LL., Yang, B., Lu, XC., et al.[2016]

In a study of 201 patients with malignant tumors, autologous cytokine-induced killer (CIK) cell infusion showed enhanced proliferation of the CD3⁺ CD56⁺ cell subpopulation when the secondary preparation was done within 90 days of the primary infusion, indicating improved therapeutic potential.

The study found that the expression of the NKG2D receptor was also higher in the ≤ 90-day group, suggesting that timely secondary CIK cell preparations can optimize their activity against cancer cells, while effects diminish after 90 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Autologous CIK cell infusion promotes amplification ability of CD3⁺ CD56⁺ cells when re-preparation from patients with malignant tumors]. Yu, H., Sun, Y., Lin, D., et al.[2017]

The study involved 82 patients with advanced renal cell carcinoma, showing that dendritic cells (DCs) sensitized with autologous tumor cell lysate significantly enhanced the immune response, particularly increasing the proliferation of cytokine-induced killer (CIK) cells and the release of IL-12.

Patients receiving the Ag-DC-CIK vaccine had better clinical responses compared to those receiving CIK cell therapy alone, with no severe adverse effects reported, indicating a promising and safe immunotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic efficacy of dendritic cells pulsed by autologous tumor cell lysate in combination with CIK cells on advanced renal cell carcinoma]. Wang, H., Feng, F., Zhu, M., et al.[2021]

Cytokine-induced killer (CIK) cell therapy significantly improved overall survival and clinical response rates in patients with non-small cell lung cancer (NSCLC), based on an analysis of 17 randomized controlled trials involving 1172 patients.

CIK therapy enhanced immune responses by increasing various T cell populations while reducing regulatory T cells, and it was associated with only a higher incidence of fever compared to chemotherapy, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy of cytokine-induced killer cell therapy in the treatment of non-small cell lung cancer. Wang, M., Cao, JX., Pan, JH., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Immunobiology of the IL-15/IL-15Rα complex as an antitumor and antiviral agent. [2018]

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

The IL-15-based superagonist ALT-803 promotes the antigen-independent conversion of memory CD8+ T cells into innate-like effector cells with antitumor activity. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A very long-acting IL-15: implications for the immunotherapy of cancer. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Biological effects of IL-15 on immune cells and its potential for the treatment of cancer. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

A homodimeric IL-15 superagonist F4RLI with easy preparation, improved half-life, and potent antitumor activities. [2022]

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

Phase I Trial Characterizing the Pharmacokinetic Profile of N-803, a Chimeric IL-15 Superagonist, in Healthy Volunteers. [2023]

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

Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. [2022]

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

IL15 by Continuous Intravenous Infusion to Adult Patients with Solid Tumors in a Phase I Trial Induced Dramatic NK-Cell Subset Expansion. [2021]

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

Short-course IL-15 given as a continuous infusion led to a massive expansion of effective NK cells: implications for combination therapy with antitumor antibodies. [2023]

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

Immunotherapy with cytokine-induced killer cells in metastatic renal cell carcinoma. [2010]

11. China pubmed.ncbi.nlm.nih.gov

[Application of immune function test to evaluate effect of cytokine-induced autologous killer cell infusion for elderly patients with hematological malignancies]. [2016]

12. China pubmed.ncbi.nlm.nih.gov

[Autologous CIK cell infusion promotes amplification ability of CD3⁺ CD56⁺ cells when re-preparation from patients with malignant tumors]. [2017]

13. China pubmed.ncbi.nlm.nih.gov

[Therapeutic efficacy of dendritic cells pulsed by autologous tumor cell lysate in combination with CIK cells on advanced renal cell carcinoma]. [2021]

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

Adoptive immunotherapy of cytokine-induced killer cell therapy in the treatment of non-small cell lung cancer. [2019]