PD-L1 t-haNK for Advanced Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ImmunityBio, Inc.

Must not be taking: Systemic corticosteroids

Disqualifiers: Autoimmune disease, Organ transplant, Inflammatory bowel, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PD-L1 t-haNK, a type of immunotherapy using modified natural killer cells, for individuals with advanced solid cancers that have spread or are difficult to remove. The main goals are to assess the treatment's safety, effectiveness, and to determine the optimal dose for future studies. Participants should have a solid tumor cancer that has not responded to previous treatments or have no other effective treatment options. 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 have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic daily treatment with systemic corticosteroids, you may need to stop, as this is listed as an exclusion criterion.

Is there any evidence suggesting that PD-L1 t-haNK is likely to be safe for humans?

Research has shown that PD-L1 t-haNK, a therapy using natural killer (NK) cells, has been tested in earlier studies. These studies found no serious side effects that would prevent doctors from increasing the dose, indicating the treatment is generally safe for patients. The therapy uses NK cells to attack cancer cells, and early results are positive for safety. This information is reassuring for anyone considering joining a clinical trial for PD-L1 t-haNK. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about PD-L1 t-haNK for advanced cancer because it leverages a novel approach using engineered natural killer (NK) cells to target cancer cells. Unlike traditional treatments for advanced solid cancers, such as chemotherapy or PD-1/PD-L1 inhibitors that rely on directly damaging cancer cells or blocking immune checkpoints, PD-L1 t-haNK harnesses the body's immune system by enhancing NK cells to recognize and attack tumors. This unique mechanism of action provides a promising alternative for patients, potentially offering more targeted and effective treatment with fewer side effects.

What evidence suggests that PD-L1 t-haNK could be an effective treatment for advanced cancer?

Research has shown that PD-L1 t-haNK cells, a type of immune cell, can help control tumor growth when combined with other treatments. These cells target cancer by recognizing a protein called PD-L1, which some cancers use to evade the immune system. Studies have found that using PD-L1 t-haNK cells with other immune therapies can effectively slow cancer spread. Importantly, early trials demonstrated that PD-L1 t-haNK treatment is safe, as no severe side effects were observed in a small group of patients with advanced cancers. This trial studies different dose levels of PD-L1 t-haNK for their potential effectiveness against various solid tumors. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic solid cancers who've had at least one prior treatment can join this trial. They need a measurable tumor, must provide a recent biopsy, and be able to follow the study's schedule. People with autoimmune diseases, organ transplants, severe heart conditions, uncontrolled hypertension, certain infections like HIV or inadequate organ function are excluded.

Inclusion Criteria

I can provide a recent biopsy sample or am willing to have one taken for the study.

Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception while on study and for at least 5 months after the last dose of PD-L1 t-haNK for Infusion. Non-sterile male subjects must agree to use a condom while on study and for up to 5 months after the last dose of PD-L1 t-haNK for Infusion. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), oral contraceptives, and abstinence

I have at least one tumor that can be measured or evaluated.

Exclusion Criteria

Body weight ≤ 50 kg at screening

Positive results of screening test for human immunodeficiency virus (HIV)

I need constant oxygen because of my advanced cancer or another illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of PD-L1 t-haNK to determine the maximum tolerated dose

Variable, up to 1 year

Dose Expansion

Participants receive the recommended phase 2 dose of PD-L1 t-haNK to assess safety and preliminary efficacy

Variable, up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PD-L1 t-haNK

Trial Overview The trial is testing PD-L1 t-haNK for safety and early signs of effectiveness in treating various solid tumors. It aims to find the highest dose patients can tolerate without serious side effects and recommend a dose for future studies.

How Is the Trial Designed?

Group I: PD-L1 t-hanK Dose Level 2 Experimental Treatment 1 Intervention

PD-L1 will be administered to patients with locally advanced or metastatic solid cancers. Planned number of subjects to be enrolled into Dose Level 2 is 3 to 6.

Group II: PD-L1 t-haNk Dose -1a (if needed) Experimental Treatment 1 Intervention

PD-L1 will be administered to patients with locally advanced or metastatic solid cancers. Planned number of subjects to be enrolled into Dose Level -1a is 3 to six, if needed.

Group III: PD-L1 t-haNK Dose Level Recommended phase 2 dose (RP2D) Experimental Treatment 1 Intervention

PD-L1 will be administered to patients with locally advanced or metastatic solid cancers. Planned number of subjects to be enrolled into RP2D is 4.

Group IV: PD-L1 t-haNK Dose Level 1 Experimental Treatment 1 Intervention

PD-L1 t-haNK will be administered to patients with locally advanced or metastatic solid cancers. Planned number of subjects to be enrolled into Dose Level 1 is 3 to 6.

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

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7247398/

PD-L1 targeting high-affinity NK (t-haNK) cells induce ... PD-L1 t-haNK cells in combination with anti-PD-1 antibody and N-803 resulted in improved tumor growth control. Other studies have reported that ...

2. nature.com nature.com/articles/s41423-024-01207-0

CAR-T and CAR-NK as cellular cancer immunotherapy for ... Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies. However, their efficacy against solid ...

3. immunitybio.com immunitybio.com/nantkwest-announces-phase-1-results-for-first-in-human-pd-l1-tumor-targeted-natural-killer-cells-pd-l1-t-hank-in-patients-with-locally-advanced-or-metastatic-solid-cancers/

NantKwest Announces Phase 1 Results for First-in-Human ... First-in-human trial shows no dose-limiting toxicities in six subjects treated as out-patients with PD-L1.t-haNK off-the-shelf CAR NK cell therapy.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6205063/

PD-L1 blockade enhances anti-tumor efficacy of NK cells - PMC Anti-PD-1/anti-PD-L1 therapies have shown success in cancer treatment but responses are limited to ~ 15% of patients with lymphocyte infiltrated, PD-L1 positive ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525001624008955

Emerging combined CAR-NK cell therapies in cancer ... Thus, it appears that combining CAR-NK cells and PD-1 and/or PD-L1 inhibitors holds promise for treating metastatic tumors.26. Activated NK ...

6. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-025-00633-8

The clinical landscape of CAR NK cells Here we explore the current clinical landscape of CAR NK cells, and their application in hematologic malignancies and solid cancers.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12290171/

Precision sniper for solid tumors: CAR-NK cell therapy - PMC However, the therapeutic efficacy of CAR-T cells against solid tumors remains suboptimal, accompanied by toxic side effects such as cytokine ...