CHECKvacc (CF33-hNIS-antiPDL1) / Imugene - LARVOL DELTA

CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jun 2025 ➔ Mar 2026 | Trial primary completion date: Jun 2025 ➔ Mar 2026

First-in-human • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

hNIS-based imaging to monitor treatment with the novel oncolytic virus CF33-hNIS-antiPDL1 in humans with advanced triple negative breast cancer. (PubMed, Front Oncol) - P1 | "This technology holds promise for noninvasive tracking of systemically administered OVs and other therapies. https://www.clinicaltrials.gov/study/NCT05081492, identifier NCT05081492."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

CF33-hNIS-antiPDL1 enhances immunogenicity and anti-tumor efficacy in an orthotopic syngeneic pancreatic cancer mouse model. (PubMed, Biomed Pharmacother) - "In conclusion, CF33-hNIS-antiPDL1 showed both immunogenic and anti-tumor activity against mouse KPC cells in vitro and in vivo, with functional expression of active anti-PD-L1 scFv. These findings support the clinical translation of CF33-hNIS-antiPDL1 as an intraperitoneal therapy in PDAC patients."

IO biomarker • Journal • Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • IFNB1 • IFNG • PTPRC

CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Sep 2024 ➔ Jun 2025 | Trial primary completion date: Sep 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Imugene granted China patent for Oncolytic Virotherapy CF33 (Investing.com) - "Imugene Ltd...has gained access to the largest pharmaceutical market in Asia with the grant of a patent for its Oncolytic Virotherapy CF33 from the Chinese Patent Office, following earlier grants in Japan and South Korea...The patent...protects the method of composition and method of use of Imugene’s licensed oncolytic virotherapy to 2037, including VAXINIA (CF33-hNIS) and CHECKvacc (CF33-hNIS-antiPDL1)."

Patent • Oncology • Solid Tumor

CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: City of Hope Medical Center | Recruiting ➔ Active, not recruiting | N=78 ➔ 9 | Trial completion date: Dec 2023 ➔ Sep 2024 | Trial primary completion date: Dec 2023 ➔ Sep 2024

Enrollment change • Enrollment closed • Metastases • Oncolytic virus • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Induction of an inflammatory tumor microenvironment with oncolytic virus CF33-hNIS-antiPD-L1 intratumoral injection in patients with metastatic triple-negative breast cancer (mTNBC) (ESMO 2023) - P1 | "Clinical trial identification NCT05081492. Upregulation of PD-L1 within the TME further suggests immune activation by CHECKvacc. The clinical trial is ongoing to further assess dose escalation, tumor response, and the potential for future combination trials with systemic therapies, such as checkpoint blockade and chemotherapy."

Biomarker • Clinical • IO biomarker • Metastases • Oncolytic virus • Tumor microenvironment • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8

Anti-Tumor Immunogenicity of the Oncolytic Virus CF33-hNIS-antiPDL1 against Ex Vivo Peritoneal Cells from Gastric Cancer Patients. (PubMed, Int J Mol Sci) - "CF33-OVs infect, replicate in, express functional proteins, and kill ex vivo GCPM cells with immune-activating effects. CF33-hNIS-antiPDL1 displays real potential for intraperitoneal GCPM therapy."

IO biomarker • Journal • Oncolytic virus • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Infectious Disease • Oncology • Solid Tumor • CD8 • EGFR • IL10 • PTPRC

Imugene to present cancer therapy platforms at prestigious ESMO Congress (Proactiveinvestors) - "Imugene Lt...is gearing up to present two of its innovative therapeutic platforms to some of the world’s most prestigious clinicians, researchers, patient advocates, journalists and industry representatives at the European Society for Medical Oncology (ESMO) Congress. The biotech stock’s B cell immunotherapy, HER-Vaxx, and its CF33 oncolytic virotherapy, CHECKVacc, will take centre stage at the major oncology event in Madrid from October 20 to October 24....Dr Tobias will discuss a Phase 2 study of HER-Vaxx, where Imugene used a HER2-targeting peptide vaccine plus standard of care chemotherapy in patients with HER2+ advanced stomach cancer."

P2 data • Breast Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer

Imugene welcomes crucial US patent milestone for CF33 oncolytic virus to 2037 (Proactiveinvestors) - "Imugene Ltd...welcomes the US Patent and Trademark Office’s (USPTO) granting of a crucial Notice of Allowance protecting the company’s oncolytic virotherapy CF33 patent until 2037. The Notice of Allowance is for the clinical stage immuno-oncology company’s patent application number 16/324,541 titled 'Chimeric Poxvirus Composition and Uses Thereof', for CF33, including VAXINIA (CF33-hNIS) and CHECKVacc (CF33-hNIS-antiPDL1)."

Patent • Oncology

Imugene welcomes new dose escalation in CHECKvacc clinical trial for triple negative breast cancer (Proactiveinvestors) - "Imugene Ltd...welcomes confirmation that renowned Los Angeles cancer research and treatment centre City of Hope will proceed with a fourth dose cohort in the Phase 1 clinical trial of the company’s oncolytic virotherapy candidate CHECKvacc. The first-in-human, Phase 1, single-centre study of CHECKvacc focuses on evaluating the safety and preliminary efficacy of the drug candidate, administered intra-tumorally, in patients with metastatic triple negative breast cancer (TNBC)."

Trial status • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Imugene fields promising imaging data tracking CHECKvacc replication in patients with triple-negative breast cancer (Proactiveinvestors) - P=1 | N=78 | NCT05081492 | "In an important proof of concept that also confirmed safety and tolerability, Imugene Ltd...has revealed new imaging data on its oncolytic virotherapy candidate, CHECKvacc (CF33-hNIS-antiPDL1), which was presented at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, Florida overnight....The company says its preliminary evaluation suggests the oncolytic virus increased CD8+ T-cell infiltration and increased PD-L1 expression following intratumoral (directly into the tumour) injection of CF33-hNIS-antiPD-L1. In other words, the company believes the use of CHECKvacc increases the efficacy of the immune system’s response to tumours, producing a therapeutic response."

P1 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Development of the oncolytic virus, CF33, and its derivatives for peritoneal-directed treatment of gastric cancer peritoneal metastases. (PubMed, J Immunother Cancer) - P1 | "Our results show that CF33-OVs can deliver functional proteins and demonstrate effective antitumor activity in GCPM models when delivered intraperitoneally. These preclinical results will inform the design of future peritoneal-directed therapy in GCPM patients."

IO biomarker • Journal • Oncolytic virus • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Infectious Disease • Oncology • Peritoneal Cancer • Solid Tumor • Triple Negative Breast Cancer

Development of the oncolytic virus, CF33, and its derivatives for peritoneal-directed treatment of gastric cancer peritoneal metastases (J Immunother Cancer) - "In the xenograft model, CF33-hNIS-antiPDL1 (IP; 3×105 pfu × 3 doses) treatment significantly reduced peritoneal tumors (p<0.0001), decreased amount of ascites (62.5% PBS vs 25% CF33-hNIS-antiPDL1) and prolonged animal survival. At day 91, seven out of eight mice were alive in the virus-treated group versus one out of eight in the control group (p<0.01)."

Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase I study of intratumoral administration of CF33-hNIS-antiPD-L1 (CHECKvacc) in patients with metastatic triple negative breast cancer (SABCS 2022) - P1 | "Background: Despite recent FDA approvals of immune checkpoint inhibitor pembrolizumab and drug-antibody conjugate in the treatment of metastatic triple negative breast cancer (mTNBC), the overall survival benefit of these therapies remains modest. CF33hNIS-antiPD-L1 administered by intratumoral injection in patients with mTNBC is safe and well tolerated at the dose levels tested. Clinical trial information: NCT05081492"

Clinical • P1 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Phase I study of intratumoral administration of CF33-HNIS-antiPDL1 in patients with metastatic triple negative breast cancer. (ASCO 2022) - P1 | "Background: Despite recent FDA approval of immune checkpoint inhibitor pembrolizumab and drug-antibody conjugate in the treatment of metastatic triple negative breast cancer (mTNBC), the overall survival benefit of these therapies remains modest. This FIH trial of CF33-hNIS-antiPD-L1 intratumoral injection in patients with mTNBC is currently underway."

Clinical • P1 data • Breast Cancer • Gene Therapies • Immune Modulation • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer

Imugene HER-Vaxx and CF33 platforms feature at ASCO Gastrointestinal Cancers Symposium (Proactiveinvestors) - "Dr Annie Yang from City of Hope presented the following results in this poster session: CF33-OVs infects and replicates in a dose dependent manner in both diffuse and intestine subtypes of human GC cell lines without attenuation caused by insertion of human transgenes; immunofluorescence imaging showed virus-encoded hNISand anti-PD-L1 antibody expression in CF33-OV-infected GC cells; CF33-OVs killed a range of GC cell lines in a dose dependent manner....in the xenograft model, CF33-hNIS-antiPDL1 (IP; 3x105pfu x 3 doses) significantly reduced peritoneal tumors (p<0.0001), decreased amount of ascites (62.5% PBS vs. 25% CF33-hNIS-antiPDL1) and prolonged animal survival (p<0.01). At day 91, 6/8 mice were alive in the virus-treated group vs. 1/8 in the control group."

Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Imugene HER-Vaxx and CF33 platforms feature at ASCO Gastrointestinal Cancers Symposium (Proactiveinvestors) - "Dr Yanghee Woo from City of Hope presented the following key takeaways from this poster session: oncolytic CF33-hNIS-antiPDL1 virus is effective in infecting and killing fresh human peritoneal cancer cells of GCPM with expression of functional anti-PD-L1 scFv; and Phase 1 trial investigating the safety and biologic activity of intraperitoneal CF33-hNIS-antiPDL1 for the treatment of GC patients with peritoneal metastases is planned."

New P1 trial • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology

Ex vivo oncolytic and immune activity of CF33-hNIS-antiPDL1 against fresh peritoneal cells from patients with gastric cancer with and without peritoneal metastases. (ASCO-GI 2023) - "CF33-hNIS-antiPDL1 is oncolytic with immune-activating effects against GCPM ex vivo and has solid potential for intraperitoneal therapy of GCPM patients."

IO biomarker • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • CSF2 • EGFR • IL10 • PTPRC

Development of a novel chimeric oncolytic viral platform, CF33 and its derivatives, for peritoneal-directed CF33-OV treatment of gastric cancer peritoneal carcinomatosis. (ASCO-GI 2023) - "CF33-OVs demonstrate effective antitumor activity and can deliver functional proteins in vitro and in vivo. CF33-hNIS-antiPDL1 treatment induced sustained regression of GCPC and prolonged survival. These promising preclinical results support peritoneal-directed strategies with CF33-hNIS-antiPDL1 in GCPC patients."

IO biomarker • Oncolytic virus • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Imugene (ASX:IMU) reports publication of CHECKVacc abstract at ASCO 2022 (Kalkine Media) - "Imugene Limited...has recently announced the publication of the CHECKVacc abstract at the 2022 Annual Meeting of the American Society of Clinical Oncology (ASCO). The abstract published at ASCO 2022 provides details about the Company’s Phase I CHECKVacc trial in adults with TNBC (triple negative breast cancer)."

P1 data • Breast Cancer • Oncology • Triple Negative Breast Cancer

PET imaging and treatment of pancreatic cancer peritoneal carcinomatosis after subcutaneous intratumoral administration of a novel oncolytic virus, CF33-hNIS-antiPDL1. (PubMed, Mol Ther Oncolytics) - "PET/CT avidity for I uptake in s.c. and peritoneal tumors was visible starting at day 7 following the first i.t. dose of CF33-hNIS-antiPDL1. We show that CF33-hNIS-antiPDL1 can help detect and kill both s.c. and peritoneal tumors following s.c. i.t. treatment."

IO biomarker • Journal • Oncolytic virus • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Immune Modulation • Inflammation • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Peritoneal Cancer • Solid Tumor

Imugene secures an oncolytic virotherapy CF33 patent in Japan (Kalkine Media) - "...Imugene Limited...The Company has been granted an oncolytic virotherapy CF33 patent in Japan...Recently, Imugene also won a new patent in Europe, which protects the method of use as well as the method of composition of the Company’s B-cell activating immunotherapy HER-Vaxx to 2036...The patent protects the Company’s oncolytic virotherapy CF33, including CHECKVacc (CF33-hNIS-antiPDL1) and VAXINIA (CF33-hNIS). The latest patent is titled 'CHIMERIC POXVIRUS COMPOSITION AND USES THEREOF'. It protects the method of composition & the method of use of the Company’s licensed oncolytic virotherapy to 2037."

Patent • Oncology

City of Hope Opens Oncolytic Virus Clinical Trial for Patients With Advanced Breast Cancer (Businesswire) - "City of Hope...today announced the opening of a first-in-human clinical trial evaluating the use of a cancer-killing oncolytic virus to treat patients with metastatic triple-negative breast cancer....The researchers seek to determine the appropriate dose of CF33-hNIS-antiPDL1 and ascertain if it is a safe and potentially effective treatment for patients with triple-negative breast cancer that is advanced or has spread to other places in the body."

New trial • Breast Cancer • Oncology

CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1; N=78; Recruiting; Sponsor: City of Hope Medical Center; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Oncolytic virus • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • CTLA4 • ER • HER-2 • PD-1 • PGR