P1/2, N=60, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P2, N=7, Terminated, ImmunityBio, Inc. | N=24 --> 7 | Unknown status --> Terminated

P1/2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=113 --> 53

P1/2, N=596, Recruiting, ImmunityBio, Inc. | Trial completion date: Dec 2027 --> Dec 2038 | Trial primary completion date: Dec 2025 --> Dec 2028

P2/3, N=190, Active, not recruiting, ImmunityBio, Inc. | Recruiting --> Active, not recruiting

P1, N=10, Completed, University of Minnesota | N=23 --> 10

P2, N=0, Withdrawn, National Cancer Institute (NCI) | N=28 --> 0 | Trial completion date: Aug 2026 --> Apr 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Nov 2024 --> Apr 2024

P1, N=18, Not yet recruiting, Dana-Farber Cancer Institute

P1/2, N=50, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P2, N=25, Recruiting, Glenn J. Hanna | Not yet recruiting --> Recruiting

P=N/A, N=6, Active, not recruiting, ImmunityBio, Inc. | Recruiting --> Active, not recruiting

P3, N=1538, Active, not recruiting, ImmunityBio, Inc. | Trial completion date: Jul 2024 --> Apr 2026 | Trial primary completion date: Jul 2024 --> Oct 2025

P2, N=25, Not yet recruiting, Glenn J. Hanna

P1/2, N=60, Not yet recruiting, National Cancer Institute (NCI)

For more than 40 years, intravesical Bacillus Calmette-Guérin (BCG) has remained the most effective treatment for non-muscle-invasive bladder cancer (NMIBC); however, tumor recurrence and progression are common, especially for those patients with carcinoma in situ (CIS).1 Therapeutic options are limited when treatment with BCG fails, and radical cystectomy remains the only curative treatment. BCG-unresponsive NMIBC criteria were developed in 2015 to identify patients for whom additional BCG would likely not be effective and to facilitate clinical trials of novel therapies.2,3.

P1, N=20, Not yet recruiting, ImmunityBio, Inc. | Trial completion date: Sep 2026 --> Mar 2027 | Trial primary completion date: Sep 2024 --> Mar 2026

P2, N=186, Recruiting, National Cancer Institute (NCI) | Phase classification: P2b --> P2

P2, N=328, Active, not recruiting, ImmunityBio, Inc. | Recruiting --> Active, not recruiting

There was a moderate decrease in HIV-producing cells in lymph nodes. Further studies are warranted to determine the impact of healthy NK cells on HIV reservoirs and if restoring NK-cell function could be part of an HIV cure strategy.

P2, N=20, Not yet recruiting, ImmunityBio, Inc. | Trial completion date: Dec 2029 --> Dec 2030 | Initiation date: Nov 2023 --> Feb 2024 | Trial primary completion date: Dec 2028 --> Dec 2029

The N-803 combined with dinutuximab and exPBNK cells significantly extended the survival of NB xenografts (Chu/Cairo, et al, JITC...C021 was generated by modifying C134 to express human IL21 gene... Our data demonstrated IL15 or IL21 based novel cytokine therapy (N-803 or C021) significantly enhanced the anti-tumor efficacy of ROR1 CAR NK targeting NB in vitro and in vivo

P1/2, N=113, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=40, Not yet recruiting, National Cancer Institute (NCI)

We, therefore, hypothesized the use of CTLA-4 blockade with ipilimumab (IPI) would deplete Tregs in vivo and thus allow enhanced proliferation, activation, and anti-tumor responses of the adoptively transferred CIML NK cells...All patients received lymphodepletion with fludarabine (25 mg/m2 x 5 days) and cyclophosphamide (60 mg/kg x 2 days) and haploidentical CIML NK cell infusion (5-10 x 106 cells/kg) followed by IL-15 superagonist (N-803) (15 mcg/kg subcutaneously) starting on day +1 every 21-days (4x)...The use of IPI was associated with a relative depletion of Tregs with concurrent expansion of CD56dimCD16+ NK cells that had enrichment of proliferative (MYC), metabolically active (mTORC1), and cytokine reactive (TNFa) gene sets. Further work is required to elucidate the mechanism by which IPI exposure is associated with the expansion of specific subsets of CIML NK cells.

In the current study, we hypothesized the use of ipilimumab (IPI) will abrogate Treg-mediated inhibition and thus allow enhanced proliferation, activation, and anti-tumor responses of the adoptively transferred CIML NK cells...All patients received lymphodepletion with fludarabine (25 mg/m 2 x 5 days) and cyclophosphamide (60 mg/kg x 2 days) during days -6 to -2 prior to haploidentical CIML NK cell infusion on day 0 (5-10 x 10 6 cells/kg=dose level 0) followed by N-803 (15 mcg/kg subcutaneously) starting on day +1 every 21-days for 4-doses...Tumor regression was associated with CD56 dimCD16 + NK cell expansion. Further work is required to elucidate the mechanism by which IPI exposure is associated with the expansion of specific subsets of CIML NK cells.

P1/2, N=50, Not yet recruiting, National Cancer Institute (NCI)

In summary, RRV-mediated RLI immunotherapy results in immunostimulatory changes that are further potentiated by systemically administered temozolomide. This tumor-localized gene therapy has the potential to synergize with standard of care treatment to reverse the immunosuppressed GBM tumor microenvironment and provide a significant treatment benefit.

P2, N=28, Not yet recruiting, National Cancer Institute (NCI) | Trial primary completion date: Nov 2023 --> Nov 2024

P1, N=36, Recruiting, Rockefeller University | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=20, Not yet recruiting, ImmunityBio, Inc.

Furthermore, co-culture with RD-IL15-secreting GD-CAR NK cells markedly enhanced proliferation and cytotoxicity of bystander immune cells in a paracrine manner. Our results demonstrate that GD-CAR NK cells co-expressing the IL-15 superagonist mediate potent direct and indirect antitumor effects, suggesting this strategy as a promising approach for the further development of functionally enhanced cellular therapeutics.

P2b, N=147, Active, not recruiting, ImmunityBio, Inc. | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: May 2023 --> May 2024

P3, N=1538, Active, not recruiting, ImmunityBio, Inc. | Trial primary completion date: Jul 2023 --> Jul 2024

P1/2, N=30, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P1, N=20, Not yet recruiting, ImmunityBio, Inc. | Initiation date: Apr 2023 --> Sep 2023

The combination of N803 with the immune checkpoint inhibitor nivolumab demonstrated encouraging clinical responses in nivolumab-naïve and nivolumab-refractory patients with non-small cell lung cancer. Currently, N803 is being evaluated preclinically and clinically in combination with various agents, including chemotherapeutics, immune checkpoint inhibitors, vaccines, and other immuno-oncology agents. This report will review the mechanism(s) of action of N803 and how it relates to the preclinical and clinical studies of N803.

P1/2, N=21, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

No abstract available

The addition of ICB with an antibody-dependent cellular cytotoxicity IgG1 antibody against PD-L1 (avelumab) or an IgG4 antibody against PD-1 (pembrolizumab) enhanced N-803 induced NK-cell function in vitro. Using models of human ovarian cancer and NK-cell adoptive transfer in mice, we showed enhanced antitumor control with N-803 and ICB, as well as a combination effect that enhanced NK-cell persistence and expansion in vivo. This work suggests that PD-1/PD-L1 blockade combined with IL15 signaling may overcome resistance to cytokine therapy in ovarian cancer.

P2/3, N=82, Active, not recruiting, SWOG Cancer Research Network | Recruiting --> Active, not recruiting | N=478 --> 82

P2b, N=186, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Aug 2023 --> Mar 2023

P2b, N=186, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2026 --> Feb 2027 | Initiation date: Nov 2022 --> Aug 2023 | Trial primary completion date: Oct 2026 --> Feb 2027