ORCA-010 / ORCA Therap - LARVOL DELTA

ORCA-010 oncolytic therapy: Inducing tumor-specific immune responses and activation of tumor microenvironment in treatment-naïve prostate cancer (ESMO-IO 2024) - P1/2 | "The increase in tumor-infiltrating and circulating prostate-specific T cells, along with stable regulatory T cells, indicates a favorable immune environment. These findings suggest that ORCA-010 can convert cold tumors into immunogenic ones, highlighting its promise for prostate cancer immunotherapy."

Biomarker • Tumor microenvironment • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • GZMB • PD-1

Proffered Paper: Oncolytic adenovirus ORCA-010 activates the tumor microenvironment and induces systemic tumor-specific T cell responses in patients with newly-diagnosed prostate cancer (EACR 2024) - P1/2 | "Crucially, ORCA-010 treatment induced a systemic increase in tumor responsive CD8 T cells. Together, this offers promise for use of ORCA-010 in prostate cancer immunotherapy strategies."

Biomarker • Clinical • Oncolytic virus • Tumor microenvironment • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD8 • IFNG • PD-1

Oncolytic Adenovirus ORCA-010 Induces Systemic Tumor-Specific T cell Responses and Activation of the Tumor Microenvironment in Prostate Cancer: A Phase I/IIa Clinical Trial (ASGCT 2024) - "The intraprostatic injection of ORCA-010 in treatment-naïve prostate cancer patients is not only safe (grade I/II AE’s), but also boosts long term anti-tumor immune responses, demonstrated by increase in tumorspecific T cells in the blood and shifting an immunologically "cold" tumor microenvironment into "hot" regions in prostate cancer. Together, these findings highlight the potential of ORCA-010 in shaping future treatment approaches in combination with standard care modalities and/or immune checkpoint inhibitors."

Biomarker • Clinical • Late-breaking abstract • Oncolytic virus • P1/2 data • Tumor microenvironment • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD8 • FOXP3 • IFNG • PD-1 • TNFA

Immunological changes in the tumor microenvironment induced by ORCA-010, an oncolytic adenovirus, in early-stage Prostate cancer: Interim results from a Phase I/IIA clinical trial (EACR-AACR 2024) - "Conclusion The intratumoral administration of ORCA-010 in treatment-naïve prostate cancer patients demonstrated an excellent safety profile, with no observed DLTs and limited grade I and II adverse events (AEs). Our findings strongly suggest that ORCA-010 administration has the potential to shift an immunologically "cold" tumor microenvironment into "hot" regions in prostate cancer, holding promise for future treatment strategies in combination with standard of care modalities or modalities that require activation of the tumor micro environment."

Biomarker • Clinical • Oncolytic virus • P1/2 data • Tumor microenvironment • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD8

First in Man Clinical Study to Evaluate Safety and Tolerability of an Oncolytic Adenovirus in Prostate Cancer Patients. (clinicaltrials.gov) - P1/2 | N=24 | Active, not recruiting | Sponsor: Orca Therapeutics B.V. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Nov 2023 ➔ Oct 2024

Enrollment closed • Oncolytic virus • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PCA3

Preclinical and early clinical evaluation of infectivity- and potency-enhanced oncolytic adenoviruses ORCA-010 and ORCA-020. (ESGCT 2023) - No abstract available

Oncolytic virus • Preclinical

Clinical assessment of ORCA-010, a replication competent oncolytic adenovirus, in treatment-naïve prostate cancer patients (SITC 2022) - No abstract available

Clinical • Oncolytic virus • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Clinical results from a phase I dose escalation study in treatment-naïve early stage prostate cancer patients with ORCA-010, a potency enhanced oncolytic replication competent adenovirus (SITC 2021) - P1/2 | "Preliminary analyses of the data demonstrate viral replication post administration, encouraging initial anti-tumor activity and a prostate size reduction in prostate cancer patients with enlarged prostates. Trial Registration NCT04097002"

Clinical • Late-breaking abstract • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • MRI

First in Man Clinical Study to Evaluate Safety and Tolerability of an Oncolytic Adenovirus in Prostate Cancer Patients. (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Orca Therapeutics B.V. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Aug 2022 ➔ Nov 2023

Oncolytic virus • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PCA3

Orca Therapeutics to start highest dose in treatment-naïve prostate cancer (PRNewswire) - “ORCA Therapeutics…announce that, upon review of all safety data from the fully enrolled, low- and mid-dose patient cohorts of the ongoing Phase 1/2a clinical study of ORCA-010 in treatment-naïve patients with localized prostate cancer, the independent Data and Safety Monitoring Board (DSMB) unanimously recommended the continuation of the study without modification. From this recommendation, ORCA Therapeutics will initiate administration of the highest scheduled dose level of ORCA-010 in the single dose part of the study…with the first patient scheduled for administration in March 2021…DSMB will conduct an additional review on ORCA-010 prior to starting the repeat dosing part of the trial.”

DSMB • Enrollment status • Genito-urinary Cancer • Oncology • Prostate Cancer

Oncolytic adenovirus ORCA-010 activates pro-inflammatory myeloid cells and facilitates T cell recruitment and activation by PD-1 blockade in melanoma. (PubMed, Hum Gene Ther) - "Observed increased rates of activated CD8 T cells, expressing CD69 and PD-1, were related to both increased CD8α cDC rates and M1/M2 shifts in tumor and spleen. In conclusion, the myeloid modulatory properties of ORCA-010 in melanoma, resulting in recruitment and activation of T cells, could enhance the antitumor efficacy of PD-1 blockade."

Journal • Oncolytic Virus • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • PD-L1

Oncolytic adenovirus ORCA-010 increases the type-1 T cell stimulatory capacity of melanoma-conditioned dendritic cells. (PubMed, Clin Exp Immunol) - "Their subsequent ability to prime effector T cells with a type-I cytokine profile was significantly increased in a subsequent allogeneic mixed leukocyte reaction. Our findings suggest that ORCA-010 is a valuable immunotherapeutic agent for melanoma."

IO Biomarker • Journal • Oncolytic Virus • Immune Modulation • Immunology • Inflammation • Melanoma • Oncology • Solid Tumor

First in Man Clinical Study to Evaluate Safety and Tolerability of an Oncolytic Adenovirus in Prostate Cancer Patients. (clinicaltrials.gov) - P1/2; N=24; Recruiting; Sponsor: Orca Therapeutics B.V.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Oncolytic Virus

First in Man Clinical Study to Evaluate Safety and Tolerability of an Oncolytic Adenovirus in Prostate Cancer Patients. (clinicaltrials.gov) - P1/2; N=24; Not yet recruiting; Sponsor: Orca Therapeutics B.V.

Clinical • New P1/2 trial • Oncolytic Virus