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 InformedConsent Form.

2. Male or female patients, ≥ 18 years of age.

3. a) Phase 1a: patients with tumours reported to be FAP positive with histological orcytological confirmation of a locally advanced (unresectable) and/or metastatic: a. salivary gland, urothelial, ovarian, or breast carcinoma, who have eitherrelapsed or progressed on SoC treatment or are intolerant or nonamenable to SoCtreatment; OR b. soft-tissue sarcoma who: i. is treatment naïve in the locallyadvanced (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 75mg/m2 Q21 days) and has discontinued due to intolerance or toxicity related todoxorubicin b) Phase 1b: patients with histological or cytological confirmation of a locallyadvanced (unresectable) and/or metastatic tumour of one of the following types:

4. high grade soft tissue sarcoma: histologically proven locally advanced ormetastatic, unresectable progressive or recurrent DDLS or UPS who have received 0 or 1 prior lines of therapy in the locally advanced or metastatic setting

5. SGC: Locally advanced or metastatic salivary gland confirmed by histopathologythat cannot be completely resected by surgery who have received 0 or 1 priorlines of therapy in the locally advanced or metastatic setting. In addition,patients with adenoid cystic carcinoma subtypes must not have received priorcytotoxic therapy for locally advanced or metastatic disease. Adenoid cysticcarcinoma subtype to be capped at 15 patients (assuming cohort of approximately 30 patients)

6. TNBC: Locally advanced or metastatic triple negative breast cancer confirmed byhistopathology who have received up to 2 lines of prior therapy in the locallyadvanced or metastatic setting. BRCA with PD-L1 negative

7. 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 nothave previously received an anthracycline-based therapy.

• Patients with TNBC may receive up to 250mg/m2 of prior doxorubicin (or anequivalent anthracycline). Prior anthracycline based therapy must have beencompleted at least 6 months before the planned Cycle 1 Day 1 AVA6000 infusion.Prior anthracycline use must have been in the adjuvant or neoadjuvant settingonly.

• Patients must provide at least 1 tissue sample collection, either archival orfresh tissue (approximately 10 slides) unless the biopsy is medically not ableto be performed or the principal investigator deems it is not medicallyfeasible.

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 receivingtherapeutic anticoagulation; patients receiving therapeutic anticoagulation shouldbe 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 musthave 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 bonemetastases, or ALP < 2 × ULN in patients without documented metastases.

10. Has adequate renal function (creatinine clearance ≥50 mL/min by Cockcroft-Gaultformula) 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 amenorrheaafter start of menopause: has a negative serum pregnancy test within 7 days prior toCycle 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 contraceptivemethod (Pearl Index failure rate <1% per year) during the treatment period andfor at least 6 months after the last dose of study drug.

• Male patients with female partners of childbearing potential must agree tousing 2 acceptable methods of contraception (Pearl Index failure rate <1% peryear), including a barrier method (with or without spermicide) during thetreatment 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 treatmentperiod 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 opinionof the Investigator or delegate, suitable for peripheral or central intravenousinfusion of AVA6000.

14. The patient is willing and able to comply with the protocol, including any PK bloodsampling requirements and agrees to return to hospital for follow-up visits andexaminations.

Exclusion Criteria:

1. Has received trastuzumab within 7 months of the planned Cycle 1 Day 1 AVA6000infusion.

2. Has received a prior total cumulative anthracycline dose of ≥ 350 mg/m2 doxorubicin (or equivalent anthracycline dose).

3. Has clinically significant or untreated central nervous system (CNS) metastases orleptomeningeal disease requiring treatment, as determined by the Investigator.

4. Patients who have any history of an active (requiring treatment) other malignancy (except any in-situ carcinoma, non-melanoma skin carcinoma and early prostate cancerwith a normal PSA) within 2 years of study entry.

5. Has a significant, uncontrolled, concomitant disease that could affect compliancewith the protocol.

6. In the opinion of the investigator, has uncontrolled hypertension (systolic bloodpressure >150 mm Hg and/or diastolic blood pressure >100 mm Hg), unstable angina,CHF (New York Heart Association (NYHA) Class >II), left ventricular ejectionfraction (LVEF) <55% or the low limit of institutional normal limit (whichever islower) by echocardiogram (ECHO), serious cardiac arrhythmia requiring treatment (exceptions include atrial fibrillation, paroxysmal supraventricular tachycardia),history of myocardial infarction within 6 months prior to Cycle 1 Day 1, or historyof uncontrolled cardiovascular disease or high-sensitivity troponin above normal atbaseline (T or I).

7. Has a screening baseline mean corrected QTcF interval by Fridericia (QTcF) of >480msec. Electrocardiograms (ECGs) will be evaluated locally at the investigator site.Has any clinically significant abnormalities in rhythm, conduction, or morphology ofresting ECG (e.g., complete left bundle branch block, third degree heart block,second degree heart block, PR interval >250 msec). Has any factors that increase therisk of QTc prolongation or risk of arrhythmic events such as heart failure,hypokalaemia, congenital long QT syndrome, known family history of long QT syndromeor unexplained sudden death under 40 years of age in first degree relatives or anyconcomitant medication known to prolong the QT interval, a baseline restingbradycardia <45 beats/min or a baseline resting tachycardia of >100 beats/min.

8. HIV infection:

• Patients with an AIDS-defining infection within 12 months of planned study Day

• Patients on anti-retroviral treatment who are not established onanti-retroviral treatment for ≥4 weeks and who have a viral load > 400copies/mL prior to study Day 1.

9. Active hepatitis B (HBV) or hepatitis C (HCV) infection defined as:

10. Has a positive hepatitis B surface antigen (HBsAG) test at screening. Patientswith a past or resolved HBV infection (defined as having a negative HBsAG testand a positive antibody to hepatitis B core antigen [antiHBc] antibody test)are eligible.

11. Patients positive for HCV antibody are eligible only if PCR is negative for HCVRNA.

12. Chronic HBV (HbSAg positive, undetectable or low HBV DNA and normal ALT).

13. Patients with active disease who have not on/initiated anti-retroviraltreatment prior to study Day 1.

14. Patients with untreated HCV infection or have not completed treatment for HCVinfection.

15. Patients with treated HCV infection but with a HCV viral load above the levelof quantification.

16. Has a severe infection (requiring iv treatment) within 21 days prior to Cycle 1, Day 1 including, but not limited to, hospitalisation for complications of infection,bacteraemia, or severe pneumonia.

17. Has any other clinically significant active disease, metabolic dysfunction, physicalexamination finding, clinical laboratory finding, or reasonable suspicion of adisease or condition that would contraindicate the use of an investigational drug inthe opinion of the investigator.