Activation of human peripheral T cells by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted in upregulation of IL-2/15Rβ (CD122) receptor subunit in nearly all CD8+ and majority of CD4+ T cells, suggesting that TDB treatment may sensitize T cells to the IL-15. In summary, our results support the hypothesis where the number of tumor infiltrating T cells is rate limiting for the activity of solid tumor targeting TDBs. Upregulation of CD122 by TDB treatment and the observed synergy with XmAb24306 and T cell bispecific antibodies supports clinical evaluation of this novel immunotherapy combination.

P1, N=35, Not yet recruiting, Actym Therapeutics, Inc.

Daratumumab (dara), a monoclonal antibody (mAb) that targets CD38 results in antibody-dependent cellular cytotoxicity (ADCC) of both multiple myeloma (MM) cells and NK cells. Because NK cells express CD38, XmAb24306 increases dara-mediated NK cell fratricide, but overall does not negatively impact the ADCC activity against a MM cell line likely due to increased NK cell activity of the surviving cells. These data show that XmAb24306 increases direct and ADCC-mediated human NK cell cytotoxicity in vitro.

P2, N=97, Recruiting, Virogin Biotech Canada Ltd | Phase classification: P2a/2b --> P2 | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Oct 2025

P1, N=18, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | Trial completion date: Jan 2027 --> Feb 2026 | Trial primary completion date: Jan 2027 --> Feb 2025

P1, N=0, Withdrawn, Masonic Cancer Center, University of Minnesota | N=34 --> 0

P1/2, N=60, Active, not recruiting, HCW Biologics | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2

P1, N=33, Suspended, Masonic Cancer Center, University of Minnesota | Recruiting --> Suspended

These results support the rationale to improve PK and anti-tumor efficacy of IL-15 by increasing local concentrations at the tumor site via conjugation to a TA-MUC1 binding mAb. The tumor-selective expression pattern of TA-MUC1, powerful immune activation and anti-tumor cytotoxicity, long serum half-life and tumor targeting properties, render GT-00AxIL15 a promising candidate for treatment of solid tumors with high medical need, e.g., ovarian, lung and breast cancer.

Collectively, these findings support the suitability of SON-1210 for patient trials in terms of activity, efficacy, and safety, offering a promising opportunity for solid tumor immunotherapy. Linking cytokine payloads to a fully human albumin binding domain provides an indirect opportunity to target the TME using potent cytokines in cis that can redirect the immune response and control tumor growth.

P1, N=50, Active, not recruiting, IGM Biosciences, Inc. | Recruiting --> Active, not recruiting

P1, N=60, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business decision and not due to any safety concerns

P1, N=45, Terminated, Kadmon, a Sanofi Company | Trial completion date: Jul 2026 --> Dec 2023 | Recruiting --> Terminated | Trial primary completion date: Sep 2025 --> Dec 2023; Sponsor's decision.

P1, N=11, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Trial primary completion date: Dec 2025 --> Jan 2024

P1, N=50, Recruiting, IGM Biosciences, Inc.

P1/2, N=240, Recruiting, Sanofi | Trial completion date: Jun 2027 --> Mar 2028 | Trial primary completion date: Apr 2027 --> Jan 2027

P1, N=51, Recruiting, Kadmon, a Sanofi Company | N=80 --> 51

P1, N=11, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | N=50 --> 11

P1, N=250, Recruiting, Genentech, Inc. | Phase classification: P1a/1b --> P1

P2, N=40, Recruiting, CNBG-Virogin Biotech (Shanghai) Ltd.

P1b, N=92, Active, not recruiting, BJ Bioscience, Inc. | Recruiting --> Active, not recruiting

P1/2, N=36, Not yet recruiting, CNBG-Virogin Biotech (Shanghai) Ltd.

NIZ985 was well tolerated in the single-agent and NIZ985/spartalizumab regimens. The RDE was established at 1 µg/kg TIW. Antitumor activity of the combination was observed against tumor types known to have a poor response to ICIs.

iPSC-derived NK therapy offers a standardized, off-the-shelf option for NK cell therapies. FT538 iPSC-derived NK cells induce apoptosis in AML cell lines and patient samples in a dose-dependent manner and show a synergistic effect with Venetoclax, Gilteritinib, Azacitidine, and Cytarabine. Therefore, iPSC-derived NK cell therapy may be a promising possibility for AML treatment, particularly for patients resistant to standard therapies.

We hypothesized that the addition of Dara to fludarabine and cyclophosphamide would enhance lymphodepletion and augment ADCC for CD38+ AML leading to better response rates when combined with FT538. FT538 in combination with daratumumab has been tolerated in a highly pre-treated cohort of patients with expected toxicities and a signal of efficacy.

P1, N=98, Terminated, Fate Therapeutics | Trial completion date: May 2039 --> Sep 2023 | Active, not recruiting --> Terminated | Trial primary completion date: May 2024 --> Sep 2023; The study was terminated by the Sponsor.

Enrolment continues in the QW schedule. Conclusions SAR445710 demonstrated a manageable toxicity profile with on-mechanism pharmacodynamics consistent with IL-15 agonism.

Nanostring analysis of paired biopsies from the PR pts demonstrated upregulation of integrin signaling pathway, antigen-presenting MHC (HLA-DQA1 and HLA-DRB1) and chemokine receptor (CMKLR1) genes, and activation of CD8+ T cells. Conclusions Monotherapy with VG2025 demonstrated activity with a well-tolerant safety profile in pts with advanced solid tumors that progressed after standard of care therapy.

5 mg/kg in heavily pretreated advanced solid tumor patients resulted in immune cell activation, proliferation, and infiltration into the tumor microenvironment without causing unacceptable toxicity. HCW treatment presents a promising approach to enhancing the antitumor activity of immune checkpoint inhibitors in patients with solid tumors.

P1, N=36, Terminated, Virogin Biotech Australia Pty. Ltd. | Recruiting --> Terminated

P1, N=16, Terminated, Fate Therapeutics | Trial completion date: Aug 2025 --> Aug 2023 | Active, not recruiting --> Terminated; This study was terminated by the Sponsor.

P1/2, N=43, Recruiting, CNBG-Virogin Biotech (Shanghai) Ltd.

P2a/2b, N=97, Recruiting, Virogin Biotech Canada Ltd | Not yet recruiting --> Recruiting | N=41 --> 97

The study is enrolling participants. Lu D et al, J Immunother Cancer (2020); 8(Suppl 3):573.

Clinical trial identification EudraCT 2109-0040690-42. The RDE was declared as 12 μg/kg NIZ985 SA and in combination. Additional pts with NSCLC have enrolled in EXP with tislelizumab.

P1, N=36, Terminated, Pfizer | Completed --> Terminated; Pfizer has made an internal business decision to not continue further development of PF-07209960. This decision was not based on safety or regulatory considerations

P1, N=80, Recruiting, Kadmon, a Sanofi Company | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Jul 2025 --> Feb 2026

P1, N=24, Recruiting, UNC Lineberger Comprehensive Cancer Center | Not yet recruiting --> Recruiting

P1b, N=0, Withdrawn, Fate Therapeutics

P1, N=36, Completed, Pfizer | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> May 2023 | Trial primary completion date: Feb 2024 --> May 2023

Therefore, hetIL-15, a cytokine directly affecting lymphocytes and inducing cytotoxic cells, also has an indirect rapid and significant effect on the recruitment of myeloid cells, initiating a cascade for tumor elimination through innate and adoptive immune mechanisms. The intratumoral CD103CD11bDC population induced by hetIL-15 may be targeted for the development of additional cancer immunotherapy approaches.

P1, N=60, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2024 --> Nov 2023 | Trial primary completion date: Jul 2024 --> Nov 2023