P1/2, N=263, Recruiting, Salubris Biotherapeutics Inc | N=149 --> 263

P1, N=21, Active, not recruiting, M.D. Anderson Cancer Center | N=30 --> 21 | Recruiting --> Active, not recruiting

P1, N=150, Recruiting, Nkarta Inc. | Trial primary completion date: Dec 2023 --> Aug 2024

P1/2, N=52, Recruiting, Obsidian Therapeutics, Inc. | N=32 --> 52

P1, N=26, Not yet recruiting, Century Therapeutics, Inc.

Our findings identified TIGIT as a promising therapeutic target for LUAD. LUAD could benefit more from the combined therapy of IL-15 stimulation and TIGIT blockade.

P1, N=108, Recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

The ability to isolate functional NK-EVs on a large scale and use them with platinum-based drugs may lead to new clinical applications. The results of the present study suggest the possibility of the combination of NK-cell-derived EVs and CBP as a viable immunochemotherapeutic strategy for resistant cancers.

P1, N=108, Not yet recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd.

Treatment of patients with GC/GEJC with GEN-001 in combination with avelumab in the ≥ 3L setting showed promising antitumor activities with an overall manageable safety profile. The results from this trial will be updated about its effects on clinical outcome, including survival, safety, and biomarker findings. Clinical trial information: NCT05419362.

Two study arms shows similar data respect to clinical outcome. Patients infused with IL-15-stimulated NK cells showed similar toxicity to the alloreactive NK group. According to dose escalation, we observed no association between increased toxicity and increased number of infused NK cells.

The immune stimulatory mechanisms triggered by NL-201 and RT resulted in superior tumor growth inhibition and survival benefit in both localized and metastatic cancers. Our results support further preclinical and clinical investigation of this novel synergism regimen in locally advanced and metastatic settings.

Cycles 1 and 2 included three days of standard Fludarabine and Cyclophosphamide lymphodepletion (LDC), cycles 3 and 4 were given with no LDC. The treatment was associated with changes in tumor microenvironment within 8 days post-infusion, augmentation of adaptive T cell responses, and tumor shrinkage. Updated data will be presented at the conference.

P2, N=42, Active, not recruiting, Genome & Company | Recruiting --> Active, not recruiting

P2, N=148, Recruiting, Genome & Company | Not yet recruiting --> Recruiting

P1/2, N=32, Recruiting, Obsidian Therapeutics, Inc. | Active, not recruiting --> Recruiting

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.

P1/2, N=32, Active, not recruiting, Obsidian Therapeutics, Inc.

Response will be assessed every 9 weeks per RECIST v1. 1.

P2, N=42, Recruiting, Genome & Company | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

Conclusions At the dose levels evaluated to date, JK08 has been well tolerated, demonstrating preliminary disease stability & anticipated modulation of target immune cell populations in aggressive heavily pre-treated solid tumors. These results provide an initial characterization of JK08 biology & activity.

P1/2, N=140, Recruiting, SUNHO（China）BioPharmaceutical CO., Ltd. | Not yet recruiting --> Recruiting

In addition to safety and efficacy endpoints, the trial will evaluate exploratory PK, immunogenicity and pharmacodynamic endpoints including evaluations of tumor cfDNA, iNK tumor trafficking and serum cytokines. Clinical trial information: NCT05336409.

Monotherapy activity was observed with an acceptable safety profile in heavily pretreated pts with advanced solid tumors. Clinical trial information: NCT05266612.

P1; N=192; Recruiting; Sponsor:Jiangsu Simcere Pharmaceutical Co., Ltd.

Importantly, TriKE triggered NK cell responses from patients at all stages of disease and treatment, suggesting TriKE can enhance current therapies. These pre-clinical studies suggest mesothelin-targeted TriKE has the potential to overcome the immunosuppressive environment of NSCLC to treat disease.

Four tumor specific expansion cohorts will be initiated once dose and schedule are established from dose escalation and include melanoma, breast cancer, colorectal cancer, and a basket of advanced solid tumors. Response will be assessed every 9 weeks per RECIST v1.1.

CNTY-101 is an induced Pluripotent Stem Cell (iPSC) derived Chimeric Antigen Receptor (CAR) NK cell clinical candidate for the treatment of B-cell malignancies...In addition, we identify biomarkers measured during the differentiation process that are correlated with functional performance, such as the level of CD94 surface expression and tumor killing. Finally, we discuss the application of functional multi-omics to candidate clone nomination for Century Therapeutics’ pipeline of future products.

The indications of IAP0971 include lung cancer, cervical cancer, head and neck squamous cell carcinoma, liver cancer, lymphoma, and other malignant tumors. A Phase I/IIa clinical trial to evaluate the safety, tolerability and preliminary efficacy of IAP0971 in patients with locally advanced or metastatic malignant tumors is currently on-going (NCT05396391).

We previously showed that melanoma TILs engineered to express membrane-bound IL15 (mbIL15) under the control of the ligand acetazolamide (ACZ) can achieve IL2-independent expansion during manufacturing, antigen-independent persistence in vitro and anti-tumor efficacy in vivo. Unlike unengineered TILs, cytoTIL15 cells + ACZ persisted in an antigen-free setting without IL2, were cytotoxic to autologous PDc and released IFNγ in response to autologous PDx tumor digest. Taken together, these data show that IL2-independent, fully functional cytoTIL15 cells can successfully be generated from tumors such as NSCLC, HNSCC & TNBC, which afflict large numbers of patients.

IAP0971 has demonstrated a favorable safety profile and potent anti-tumor activities in vivo. A Phase I/IIa clinical trial to evaluate the safety, tolerability and preliminary efficacy of IAP0971 in patients with advanced malignant tumors is on-going (NCT05396391).

These iiT8 cells integrate the innate natural killer cell activity with adaptive T cell longevity, promising an interesting therapeutic potential. Our study demonstrates that innate T cells, albeit of limited clinical applicability given their low frequency, can be efficiently generated from peripheral blood and applied for adoptive transfer, CAR therapy, or combined with therapeutic antibodies.

P1, N=75, Recruiting, Century Therapeutics, Inc. | Not yet recruiting --> Recruiting | Trial primary completion date: Jan 2025 --> Aug 2025

P1/2, N=149, Recruiting, Salubris Biotherapeutics Inc

Our pre-clinical study demonstrates, NK cells labelled with NBs can enable a safe assessment of NK trafficking to various organs by ultrasound. Further studies will be conducted in a solid tumor (Raji lymphoma flank tumor) mouse with and without stimuli (IL-15 or chimeric antigen receptor) to alter the NK trafficking pattern to further understand the potential of this technology in the context of solid tumors.

In the initial study, the iNK cell backbone (iNK cells without the α3 MICA/B CAR) induced potent activity against the AML cell line HL60, and displayed further enhancement of activity with the addition of anti-CD33 TriKE (GTB-3650), representing combined effects of natural cytotoxicity and antibody-dependent cellular cytotoxicity. Studies with primary AML targets, +/- preincubation of decitabine and all-trans retinoic acid, known to upregulate NKG2D ligands in AML, are in progress and will be discussed. In summary, dual-targeting strategies using off-the-shelf CAR NK cells targeting α3 MICA/B in combination with antigen-specific TriKE targeting CD33 represent an ideal clinical strategy to enhance efficacy and durability of treatment in advanced AML.

B7-H3 TriKE may be particularly useful for patients with bone lesions or as consolidative therapy. Commercial manufacturing of B7-H3 TriKE (GTB-5550) has begun, and a phase I trial is expected in late 2023.

In summary, preclinical evaluation of SENTI-202 demonstrated selective killing of CD33 and/or FLT3 expressing AML cell lines while protecting healthy HSCs and HPCs. This selectivity is imparted by the novel logic-gated gene circuit engineered into healthy adult NK cells. Clinical evaluation of SENTI-202 is planned to evaluate the safety and efficacy in patients with hematologic malignancies with high unmet need, including AML.

Conclusions This is the first comprehensive study to evaluate the composition of sip-T from mCRPC patients using high dimensional CyTOF analysis, and serves as an important reference source for further modification and improvement of sip-T efficacy. Furthermore, our data is the first to show that the addition of IL-15 to sip-T could potentially enhance the efficacy of sip-T in mCRPC patients.

As proof of concept, a clinical trial of GTB-3550 (a CD33-targeted Tri-specific Killer Engager [TriKE] in AML) induced endogenous NK cell expansion and activation in refractory AML patients. Here we developed GTB-5550 (a B7H3 TriKE) as a novel dual camelid (cam) TriKE containing WT IL-15 and comprised of two cam engagers: targeting CD16 on NK cells and B7H3 on multiple solid tumors...Conclusions B7H3 TriKE delivers an NK cell specific IL-15 signal to expand NK cells and is highly specific against a broad array of cancers. Clinical manufacturing is underway with an IND planned to open clinical trials in 2023 in a number of solid tumors and multiple myeloma.