Treatments and/or Procedures

Study Criteria

Key Inclusion Criteria:

  1. Willing and able to give written informed consent

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

  3. Histological or cytological confirmation of a locally advanced (unresectable) and/or
     metastatic pancreatic (PDAC), CRC, NSCLC, HNSCC, CUP, ovarian, breast, soft tissue
     sarcoma, bladder, oesophageal, prostate, and biliary tract cancer, who have either
     relapsed or progressed on SoC treatment or are intolerant or nonamenable to SoC
     treatment

  4. In Phase 1b part of the study only: At least 1 lesion, not previously irradiated, that
     can be accurately measured at baseline as ≥10mm in the largest diameter (except lymph
     nodes, which must have a short axis ≥15 mm) with CT or MRI scan and that is suitable
     for accurate repeated measurements.

  5. Life expectancy of greater than 12 weeks, in the opinion of the investigator

  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

  7. 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. Adequate haematological function (applies only to patients not receiving therapeutic
     anticoagulation; patients receiving therapeutic anticoagulation should be on a stable
     dose):

       1. Neutrophil count of ≥1.5× 10^9 cells/L

       2. Haemoglobin ≥9g/dL (with or without transfusion support)

       3. Platelet count of ≥75,000/μL (without transfusion within 2 weeks prior to Cycle
          1, Day 1)

       4. International normalised ratio (INR) and activated partial thromboplastin time
          (aPTT) ≤1.5 times the upper limit of normal (ULN)

  9. Adequate liver function:

       1. Total bilirubin ≤1.5 × ULN (in patients with Gilbert's Syndrome, <3 × ULN is
          allowed)

       2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN
          (in patients with liver metastases, <5 × ULN is allowed)

       3. Alkaline phosphatase (ALP) <5 × ULN (patients with documented liver or bone
          metastases only)

 10. Adequate renal function:

     a. Serum creatinine ≤1.5 × ULN (in patients for whom, in the Investigator's judgment,
     serum creatinine levels do not adequately reflect renal function, creatinine clearance
     by Cockcroft-Gale formula ≥ 50 mL/min may be used)

 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:

       1. 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

       2. Male patients with female partners of childbearing potential must agree to use 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

Key Exclusion Criteria:

  1. Received trastuzumab within 7 months of the planned Cycle 1, Day 1 AVA6000 infusion

  2. Received a prior total cumulative anthracycline dose of >350mg/m^2 doxorubicin
     hydrochloride (or equivalent anthracycline dose)

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

  4. Has leptomeningeal disease

  5. Any history of an active (requiring treatment) other malignancy (except any in-situ
     carcinoma, non-melanoma skin carcinoma and early prostate cancer with a normal PSA)
     within 2 years of study entry

  6. Has a significant, uncontrolled, concomitant disease that could affect compliance with
     the protocol

  7. Has uncontrolled hypertension (systolic blood pressure [SBP] >150 mmHg and/or
     diastolic [DBP] >100 mm Hg), unstable angina, congestive heart failure (New York Heart
     Association (NYHA) Class >II), left ventricular ejection fraction (LVEF) <55% or the
     low limit of institutional normal limit (whichever is lower) 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; history of uncontrolled
     cardiovascular disease or high-sensitivity troponin above normal at baseline

  8. Screening baseline mean QTcF interval (Fridericia's) of >470 msec, obtained from 3
     electrocardiograms (ECGs). Has any clinically significant abnormalities in rhythm,
     conduction, or morphology of resting ECG (e.g., complete left bundle branch block,
     third-degree heart block, second-degree heart block, PR interval >250msec). Has any
     factors that increase the risk of QTc prolongation or risk of arrhythmic events such
     as heart failure, hypokalaemia, congenital long QT syndrome, known family history of
     long QT syndrome or unexplained sudden death under 40 years of age in first degree
     relatives or any concomitant medication known to prolong the QT interval, a baseline
     resting bradycardia <45 beats/min or a baseline resting tachycardia of >100 beats/min

  9. Known uncontrolled HIV infection

 10. Active hepatitis B (HBV) or hepatitis C (HCV) infection:

       1. Positive hepatitis B surface antigen (HBsAG) test at Screening. Patients with a
          past or resolved HBV infection (defined as having a negative HBsAG test and a
          positive antibody to hepatitis B core antigen [antiHBc] antibody test) are
          eligible.

       2. Patients positive for HCV antibody are eligible only if PCR is negative for HCV
          RNA

 11. 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

 12. Any other clinically significant active disease, metabolic dysfunction, physical
     examination finding, clinical laboratory finding, or reasonable suspicion of a disease
     or condition that would contraindicate the use of an investigational drugin the
     opinion of the investigator.

 13. Major surgery within 21 days prior to Cycle 1, Day 1 (excluding biopsies) or
     anticipates the need for major surgery during study treatment

 14. Has dementia or altered mental status that in the opinion of the investigator would
     preclude providing informed consent

 15. Pregnant or breastfeeding woman

 16. Known hypersensitivity to any of the components of AVA6000 or any excipient related to
     the product

 17. Received prior investigational therapy (defined as a treatment for which there is no
     Regulatory Authority-approved indication) within 21 or 42 days of Cycle 1 Day 1, for
     small molecule and biologic investigational therapies, respectively.

 18. Received any approved anticancer therapy, including chemotherapy or hormonal therapy,
     within 28 days prior to Cycle 1, Day 1, with the following exceptions:

       1. Hormone-replacement therapy or oral contraceptives

       2. Tyrosine kinase inhibitors (TKIs) that have been discontinued more than 7 days
          prior to Cycle1, Day 1

 19. Is planned for on study treatment or has received within 21 days prior to Cycle 1, Day
     1: St John's Wort, any strong inhibitor or inducer of CYP3A4, CYP2D6, narrow
     therapeutic index CYP1A2, CYP2B6, or P-glycoprotein (PGP) ̧ or any moderate OATP1B3
     inhibitor (will include statins)

 20. Received systemic immunosuppressive medication (for any indication) at doses of >10mg
     prednisolone (or equivalent) within 28 days prior to Cycle 1, Day 1.

 21. Received radiotherapy within 28 days prior to Cycle 1, Day 1, except for limited field
     palliative radiotherapy. Patients who have received prior or concomitant radiotherapy
     to the mediastinal area are also excluded.