A Study of CodaLytic, an Intratumoral Oncolytic Virus, in Patients With Breast Cancer

Phase 1 Study of CodaLytic, an Intratumoral Influenza-based Oncolytic Virus, in Patients With Metastatic or Otherwise Inoperable Breast Cancer

The goal of this phase 1 open label clinical trial is to evaluate the safety and preliminary efficacy of CodaLytic, an intratumorally-administered oncolytic virus, in patients with metastatic or otherwise inoperable breast cancer.

The main questions it aims to answer are:

• How safe is CodaLytic when administered in escalating dosing groups into targeted lesions?
• What is the impact of CodaLytic on lesion response and disease progression?

Eligible participants will be enrolled into four (4) escalating dose groups and treated with Codalytic through injection into a selected lesion(s) over twelve (12) weeks and then followed for up to one (1) year after the first dose. A safety committee will review the safety profile of each dosing group before the next dose-escalation.

Study procedures will include physical examinations, injection site assessments, biopsies, imaging, and collection of blood/urine to assess safety, the body's immune response, and efficacy.

This study is a Phase 1, open-label, 3+3 dose-escalation, clinical trial to evaluate the safety and preliminary efficacy of CodaLytic in patients with metastatic or otherwise inoperable breast cancer.

After providing informed consent, screened participants will undergo baseline safety assessment and imaging. The Investigator will select an accessible lesion for intratumoral injection of CodaLytic (the injected lesion), and a core needle biopsy sample of this lesion will be obtained for eligible participants to be dosed. The Investigator will also select additional lesions for imaging (target lesions); these target lesions will not be injected or biopsied. If possible, another accessible lesion that is not a target lesion will be selected for biopsy to assess abscopal effect.

Three (3) eligible participants who meet all study inclusion and no exclusion criteria will be enrolled in each of four (4) escalating-dose cohorts and administered intratumoral CodaLytic. Up to 3 additional participants per cohort may be enrolled. During the dosing period, participants will be assessed for adverse events, serious adverse events, and dose-limiting toxicities. A safety review committee will review the safety data through Day 28 for the participants in Cohort 1 before participants are enrolled in Cohorts 2 and 3 and safety data through Day 28 for the participants in Cohorts 2 and 3 before participants are enrolled in Cohort 4. The safety review committee will also meet on an ad hoc basis to review any unexpected safety concerns.

Enrolled participants will be followed for adverse events, serious adverse events, dose-limiting toxicities to assess safety of CodaLytic administration. Biopsy samples of the injected lesion and, if possible, from a noninjected, nontarget lesion will be collected at Week 5. At the end of treatment, imaging will be performed for staging by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, and biopsy samples will be collected. Repeat disease assessment will be performed 4 to 8 weeks after the Month 3/EOT visit if complete response (CR) or partial response (PR) is observed at that visit or if progressive disease (PD) is seen at that visit and the participant has not begun additional cancer treatment. After the treatment period, participants may enroll in other studies or be managed with other treatment modalities as indicated, but follow-up assessments of Investigator-assessed tumor response and anticancer treatments will be recorded at Months 6 and 12.

Inclusion Criteria:

• Women or men with metastatic or inoperable, histologically confirmed breast cancer
• Has no alternative treatment of proven benefit available or has refused treatment
• Expected survival ≥ 3 months
• At least 2 measurable lesions according to RECIST 1.1, without contraindication for repeated injections and core needle biopsies
• Adequate organ function
• Eastern Cooperative Oncology Group performance status of 0 to 2
• Negative pregnancy test, if female
• Agreement to practice a highly effective method of contraception
• Agreement to no sperm donation through 28 days, if male
• Willing to provide consent to perform study procedures

Exclusion Criteria:

• Pregnant or lactating women
• Anticancer therapy within 3 weeks of dosing
• Known active central nervous system metastases (with some exceptions)
• Presence of a concurrent malignancy for which the natural history or treatment has the potential to interfere with the safety or efficacy assessment of the Investigational Product
• Uncontrolled or severe cardiovascular disease
• Immunodeficiency or use of therapies expected to impair the immune response within thirty (30) days of enrollment or during dosing.
• Ongoing toxicity > Grade 1 from prior treatment except those which are stable
• History of severe reaction (ie, anaphylaxis) to vaccination or immunotherapy
• Planned radiation to lesions targeted for assessment/injection within 60 days before first dose or any planned radiation during dosing period
• Any condition or occupational or other responsibility that in the judgment of the Investigator would interfere with or serve as a contraindication to protocol adherence, assessment of safety, or a participant's ability to give informed consent