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954 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
  1. Tereza Brachtlova1,
  2. Allan Abramovitch2,
  3. Jonathan Giddens3,
  4. Peter Incze4,
  5. Kenneth Jansz5,
  6. Richard Casey4,
  7. Victor van Beusechem6 and
  8. Wenliang Dong1
  1. 1ORCA Therapeutics BV, Den Bosch, Netherlands
  2. 2Urology and Male Infertility Clinic, Scarboropugh, Canada
  3. 3Jonathan Giddens Medicine Professional Corp, Brampton, Canada
  4. 4The Fe/Male Health Centres, Oakville, Canada
  5. 5G. Kenneth Jansz Medicine Professional Corp, Burlington, Canada
  6. 6Amsterdam University Medical Center, Amsterdam, Netherlands


Background Oncolytic adenoviruses have proven to be clinically promising immunotherapeutic agents for the treatment of cancer. Besides the direct anti-tumor activity of oncolytic adenoviruses, their ability to create a favorable microenvironment for the action of the host immune system against unique cancer cell determinants and a non-compromised host immune system are recognized as a key factors in successful oncolytic cancer treatment.

Considering the role of the host immune system, treatment-naive patients with early stage localized prostate cancer were enrolled in a phase I trial with ORCA-010. Here we report on the safety of intratumoral administration of ORCA-010 and present an interim analysis of the clinical and immunological responses observed.

Methods Treatment-naïve prostate cancer patients with localized disease (stage I or II) were treated with a single intratumoral administration of ORCA-010 in a phase I dose escalation study. Nine patients in three dose escalation cohorts (1E11, 1E12 or 1.5E12 viral particles/administration) were treated based on a 3+3 design with a 1-year follow-up period.

The primary study objectives include the safety profile of intratumoral administration of ORCA-010. Secondary objectives include 1) evaluation of the biological activity and antitumor efficacy of intratumoral administration of ORCA-010; 2) to evaluate potential antitumor immune responses and 3) to assess shedding of ORCA-010.

Results Nine patients with localized prostate cancer have been treated with a single intratumoral administration of ORCA-010. The safety profile demonstrated excellent tolerability and safety of ORCA-010 treatment with no DLTs reported. Treatment related adverse events observed in all patients were limited to transient grade I and grade II adverse events.

Shedding analyses demonstrated active replication of ORCA-010 post administration and a viremia peak was observed in all patients within 1 week post administration. Coinciding with the viral load, free PSA increased significantly post treatment and returned to under 10 ng/mL 1-2 months post administration. Preliminary analyses of the MRI data of the low dose cohorts demonstrated a significant reduction of prostate size 6 months post treatment in patients with significantly enlarged prostates prior to treatment.

Conclusions Intratumoral administration of ORCA-010 in treatment-naïve prostate cancer patients demonstrated an excellent safety profile, with no DLTs observed and transient grade I and II adverse events. 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

Ethics Approval The study was approved by Advarra institutional review board IRB#00000971 and patients completed an ICF prior to enrollment into the study.

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