A Study Evaluating the Safety, Pharmacokinetics and Early Efficacy of AVA6000 in Solid Tumours

Inclusion Criteria

• •1. The patient has been fully informed about the study and has signed the Informed Consent Form.
• •2. Male or female patients, ≥ 18 years of age.
• •3. a) Phase 1a: patients with tumours reported to be FAP positive with histological or cytological confirmation of a locally advanced (unresectable) and/or metastatic:
• •a. salivary gland, urothelial, ovarian, or breast carcinoma, who have either relapsed or progressed on SoC treatment or are intolerant or nonamenable to SoC treatment; OR b. soft-tissue sarcoma who: i. is treatment naïve in the locally advanced (unresectable) or metastatic setting and anthracycline naïve (any setting) and would otherwise be a candidate for doxorubicin hydrochloride treatment; OR ii. has received a total doxorubicin dose of \< 150mg/m2 (any setting (\< 2 cycles of 75 mg/m2 Q21 days) and has discontinued due to intolerance or toxicity related to doxorubicin
• •b) Phase 1b: patients with histological or cytological confirmation of a locally advanced (unresectable) and/or metastatic tumour of one of the following types:
• •1. High grade soft tissue sarcoma: histologically proven locally advanced or metastatic, unresectable progressive or recurrent DDLS or UPS who have received 0 or 1 prior lines of therapy in the locally advanced or metastatic setting
• •2. SGC: Locally advanced or metastatic salivary gland confirmed by histopathology that cannot be completely resected by surgery who have received 0 or 2 prior lines of therapy in the locally advanced or metastatic setting. In addition, patients with adenoid cystic carcinoma subtypes must not have received prior cytotoxic therapy for locally advanced or metastatic disease. Adenoid cystic carcinoma subtype may be capped at 15 patients (assuming cohort of approximately 30 patients)
• •3. TNBC: Locally advanced or metastatic triple negative breast cancer confirmed by histopathology who have received any prior therapy in the locally advanced or metastatic setting. Patients must be BRCA wild-type.
• •4. In Phase 1b, patients must meet the following additional criteria:
• •Patients must demonstrate (as documented, per the investigator's assessment), radiological disease progression over the 6 months (±2 months) prior to screening. However, this requirement does not apply if the patient is newly diagnosed, recurrent or newly metastatic.
• •* Patients must have measurable disease per RECIST.
• •* Patients with high grade soft tissue sarcoma or salivary gland cancer must not have previously received an anthracycline-based therapy.
• •* Patients with TNBC may receive up to 250mg/m2 of prior doxorubicin (or an equivalent anthracycline). Prior anthracycline based therapy must have been completed at least 6 months before the planned Cycle 1 Day 1 AVA6000 infusion. Prior anthracycline use must have been in the adjuvant or neoadjuvant setting only.
• •* Patients must provide at least 1 tissue sample collection, either archival or fresh tissue (approximately 10 slides) unless the biopsy is medically not able to be performed or the principal investigator deems it is not medically feasible.
• •5. Has a life expectancy of ≥12 weeks, in the opinion of the investigator.
• •6. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• •7. Has recovered from all acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure (must have resolved to CTCAE grade ≤1 or returned to baseline, except alopecia and peripheral neuropathy, which can be up to CTCAE grade 2).
• •8. Has adequate haematological function (applies only to patients not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose):
• •* Absolute Neutrophil count (ANC) of ≥1.5 × 109 cells/L.
• •* Haemoglobin ≥9.0 g/dL.
• •* Platelet count of ≥75,000/µL.
• •* International normalised ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 times the upper limit of normal (ULN).
• •9. Has adequate liver function:
• •* Total bilirubin below ULN (except for patients with Gilbert's Syndrome who must have a total bilirubin \<3 × ULN).
• •* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (in patients with liver metastases, \<5 × ULN is allowed).
• •* Alkaline phosphatase (ALP) \<5 × ULN in patients with documented liver or bone metastases, or ALP \< 2 × ULN in patients without documented metastases.
• •10. Has adequate renal function (creatinine clearance ≥50 mL/min by Cockcroft-Gault formula) or patients with normal plasmatic creatinine despite creatinine clearance \< 50 mL/min as per Cockcroft-Gault formula are eligible for the study.
• •11. Women of childbearing potential (WOCBP) and women who have ≤ 2 years amenorrhea after start of menopause: has a negative serum pregnancy test within 7 days prior to Cycle 1 Day 1.
• •12. Contraception requirements:
• •* Female patients of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method (Pearl Index failure rate \<1% per year) during the treatment period and for at least 6 months after the last dose of study drug.
• •* Male patients with female partners of childbearing potential must agree to using 2 acceptable methods of contraception (Pearl Index failure rate \<1% per year), including a barrier method (with or without spermicide) during the treatment period and for at least 6 months after the last dose of study drug.
• •* Male patients must agree to refrain from sperm donation during the treatment period and for at least 6 months after the last dose of study drug.
• •13. All patients should have peripheral veins or central line that are, in the opinion of the Investigator or delegate, suitable for peripheral or central intravenous infusion of AVA6000.
• •14. The patient is willing and able to comply with the protocol, including any PK blood sampling requirements and agrees to return to hospital for follow-up visits and examinations.