Kisima (ATP128) / Boehringer Ingelheim - LARVOL DELTA

Bimodal Effect of NKG2A Blockade on Intratumoral and Systemic CD8 T Cell Response Induced by Cancer Vaccine. (PubMed, Cancers (Basel)) - "Here, we report the impact of NKG2A blockade on antitumoral CD8 T cell immune response elicited by KISIMA-VSV-GP-TAg vaccination in tumor mouse models. Combination therapy significantly reduced the amount of vaccine-induced exhausted CD8 T cells infiltrating the tumor, resulting in short-term improved tumor growth control and prolonged mouse survival, while it also influenced the establishment of systemic effector memory CD8 T cell response. Taken together, these data show a compartment-dependent effect of NKG2A blockade on cancer vaccine-induced T cell immunity, increasing intratumoral T cell efficacy and attenuating the development of peripheral effector memory CD8 T cell response."

Journal • Oncology • CD8 • KLRC1

Development of a heterologous prime-boost vaccine in a cold and very low T-cell infiltrated mouse tumor model. (CIMT 2024) - "The treatment of LLC1-tumor-bearing mice with the novel KISIMA/VSV-GP-Ags regimen significantly increases the number and functionality of antigen-specific CD8 and CD4 T-cells in both tumor and peripheral compartments compared to control group. The significant increase in immunogenicity confirms the ability of the KISIMA/VSV-GP-Ags heterologous prime boost to generate a specific immune response against mouse tumor antigens in the very poorly infiltrated LLC1 tumor model."

IO biomarker • Preclinical • Oncology • CD4 • CD8

A Study to Evaluate ATP150/ATP152, VSV-GP154 and Ezabenlimab in Patients With KRAS G12D/G12V Mutated PDAC (KISIMA-02) (clinicaltrials.gov) - P1 | N=85 | Recruiting | Sponsor: Amal Therapeutics | Phase classification: P1b ➔ P1

Phase classification • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

Differential effect of NKG2A blockade on peripheral and intra-tumoral CD8 T cell response induced by KISIMA – VSV-GP-TAg heterologous prime-boost vaccination (SITC 2023) - "Consistently, combination treatment resulted in decreased number of long-lasting antigen-specific effector memory CD8 T cells in secondary lymphoid organs, while complete responders were only partially protected against homologous tumor rechallenge, highlighting a negative impact of NKG2A blockade on immune memory. Conclusions Taken together, these data suggest a dual role of NKG2A blockade on cancer vaccine-induced T cells, increasing early antitumoral efficacy by reducing intratumoral T cell exhaustion but impairing the establishment of long-term immunity."

IO biomarker • Oncology • CD4 • CD8 • KLRC1

ATP128 Vaccine in Combination with Ezabenlimab Promotes Antigen-Specific Immune Responses in Stage IV Colorectal Cancer in KISIMA-01 Phase 1b Trial (PEGS 2023) - No abstract available

Combination therapy • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study to Evaluate ATP150/ATP152, VSV-GP154 and Ezabenlimab in Patients With KRAS G12D/G12V Mutated PDAC (KISIMA-02) (clinicaltrials.gov) - P1b | N=85 | Recruiting | Sponsor: Amal Therapeutics

New P1 trial • Gastrointestinal Cancer • Immune Modulation • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

Antitachycardia pacing at the His bundle is safer than conventional right ventricular antitachycardia pacing in a canine myocardial ischemic injury model. (PubMed, J Cardiovasc Electrophysiol) - "His bundle ATP is safer, but not significantly more effective, than RV ATP."

Journal • Anesthesia • Cardiovascular • Myocardial Ischemia • Ventricular Tachycardia

KISIMA-01: A first-in-human trial of the heterologous prime-boost vaccine ATP128/VSV-GP128 with ezabenlimab (BI 754091) in patients with stage IV colorectal cancer (AACR 2022) - P1b | "VSV-GP128 is a recombinant vesicular stomatitis virus (VSV) carrying the glycoprotein (GP) of a non-neurotropic strain of lymphocytic choriomeningitis virus (LCMV) instead of the native VSV-GP. Clearance of ctDNA is analyzed as an exploratory endpoint. The heterologous prime-boost cohorts (ATP128/VSV-GP128) of the KISIMA-01 trial are recruiting in the US, Switzerland and Belgium."

Clinical • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BIRC5 • CEACAM5

ATP128 vaccine with ezabenlimab promotes antigen-specific immune responses in stage IV colorectal cancer in the KISIMA-01 phase 1b trial (AACR 2022) - P1b | "Analyses indicate induction of ATP128-specific immune response in the peripheral circulation and increased infiltration of TILs into liver metastases with an improved quality of T cells."

IO biomarker • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BIRC5 • CD8 • CEACAM5 • IFNG

ATP128 Clinical Therapeutic Cancer Vaccine Activates NF-κB and IRF3 Pathways through TLR4 and TLR2 in Human Monocytes and Dendritic Cells. (PubMed, Cancers (Basel)) - "Importantly, this internalization step is detemined essential for the activation of the IRF3 pathway. This study validates the design of the self-adjuvanting ATP128 vaccine for cancer immunotherapy."

IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • TLR2 • TLR4

KISIMA-01: Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal Cancer (clinicaltrials.gov) - P1b | N=96 | Recruiting | Sponsor: Amal Therapeutics | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Jul 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect. (PubMed, Cancers (Basel)) - "Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In conclusion, heterologous prime-boost vaccination possesses the ability to induce a potent anti-tumor response in both immune-excluded and immune-infiltrated mouse tumor models. Additionally, this study highlights the design of a multi-epitope vaccine for cancer immunotherapy."

Journal • Oncology • CD4 • CD8

KISIMA-01: Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal Cancer (clinicaltrials.gov) - P1b; N=96; Recruiting; Sponsor: Amal Therapeutics; N=51 ➔ 96

Clinical • Enrollment change • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • MRI • PCR

[VIRTUAL] Protein-based cancer vaccine combined with an oncolytic vaccine promotes potent antitumor immunity (ITOC 2021) - "Moreover, combining heterologous vaccination with checkpoint blockade further improved its therapeutic efficacy and the number of long-term survivors. Conclusions The KISIMA/VSV-GP heterologous prime-boost approach holds great promise for patients with primary or acquired resistance to checkpoint blockade due to its ability to induce tumor-specific T cell, improve T cell infiltration and increase tumor inflammation, even in tumors with limited permissivity for the oncolytic virus."

IO biomarker • Oncology • CD4 • CD8 • TLR4

KISIMA-01: Phase 1b Study to Evaluate ATP128, With or Without BI 754091, in Patients With Stage IV Colorectal Cancer (clinicaltrials.gov) - P1b; N=51; Recruiting; Sponsor: Amal Therapeutics; N=32 ➔ 51; Trial completion date: Apr 2022 ➔ Dec 2023; Trial primary completion date: Jul 2021 ➔ Jul 2023

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • MRI • PCR

[VIRTUAL] KISIMA-01 trial: Safety, tolerability and immunogenicity of ATP128 with or without ezabenlimab (BI 754091) in patients with stage IV colorectal cancer – preliminary results from a phase 1b study (ESMO-GI 2021) - P1b | "Preliminary analyses indicate induction of ATP128-specific immune response observable in the peripheral circulation as well as increased infiltration of TILs into liver metastases. The KISIMA-01 trial is still recruiting."

Clinical • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BIRC5 • CD8 • CEACAM5

A modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity. (PubMed, Nat Commun) - "Combining this heterologous vaccination with checkpoint blockade further improves therapeutic efficacy with long-term survival in the spectrum. Overall, heterologous vaccination with KISIMA and VSV-GP-TAA could sensitize non-inflamed tumors to checkpoint blockade therapy."

Clinical • Journal • Oncology

KISIMA-01 Investigates the Safety of ATP128 With or Without Ezabenlimab in CRC (Targeted Oncology) - "The study is a safety study that utilized doses of the vaccine alone and then also with the addition of PD-1 inhibitor as well. The primary endpoints of this was safety bleed in and this study design indeed demonstrated that the combination was safe...but also in the tumor itself and so utilization of paired biopsies in addition to peripheral monitoring."

Video

ATP128 With or Without Ezabenlimab Shows Early Promise in Stage IV Colorectal Cancer (Targeted Oncology) - "In an interview with Targeted Oncology, Scott Kopetz, MD, PhD...explained the importance of vaccine treatment strategies in CRC, and the preliminary results from KISIMA-01....Kopetz: This study is based on an understanding that CRC is a tumor type that does not have a robust immune response, in most cases. This means that there's not preformed T cells that have antigen recognition against the tumor. The combination is more effective than either component alone and can really provide a signal that we're following up now in the clinical trials."

Interview

STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity. (PubMed, Front Immunol) - "The KISIMA™ platform allows the development of protein-based cancer vaccines able to induce tumor-specific T cell response resulting in anti-tumoral efficacy in various mouse models...Combination with STINGa treatment improved the effect of therapeutic vaccination, resulting in a prolonged control and slower growth of B16-OVA and TC-1 tumors. Altogether, the results presented here highlight the potential of combining STINGa with a therapeutic protein vaccine for cancer treatment."

Journal • Inflammation • Oncology • CD4 • CD8 • IFNG • TNFA

KISIMA-01: Phase 1b Study to Evaluate ATP128, With or Without BI 754091, in Patients With Stage IV Colorectal Cancer (clinicaltrials.gov) - P1b; N=32; Recruiting; Sponsor: Amal Therapeutics

Clinical • New P1 trial • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • PCR

KISIMA-01: Phase 1b Study to Evaluate ATP128, With or Without BI 754091, in Patients With Stage IV Colorectal Cancer (clinicaltrials.gov) - P1b; N=32; Recruiting; Sponsor: Amal Therapeutics; Trial completion date: Oct 2021 ➔ Apr 2022; Trial primary completion date: Jan 2021 ➔ Jul 2021

Clinical • Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • PCR