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A Phase 1a/1b, first-in-human, open-label, non-randomised, multicenter, dose-escalation and dose -expansion study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AXA-042 as monotherapy and in combination with an anti-PD-1 monoclonal antibody (cemiplimab) in subjects with advanced solid tumours: phase 1a

ACTRN 12622000993796

Brief Summary

AXA-042 functions through a multi-cellular mechanism to re-engage the innate immune response. This first-in-human study is planned to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary efficacy, and pharmacodynamics (PD) of AXA-042 as monotherapy in subjects with advanced solid tumors.

Intervention/Treatment

  • Drug: AXA-042.

Inclusion Criteria

  1. Diagnosis of a histologically or cytologically confirmed locally advanced or metastatic cancer (all solid tumors). Subjects must be considered refractory or intolerant to the standard of care therapies or have refused standard therapy.
  2. Age greater than or equal to 18 years old at the time of Screening (signing the Informed Consent Form [ICF]).
  3. Eastern Cooperative Oncology Group performance status 0 to 1.
  4. The estimated life expectancy of at least 3 months as per the Investigator’s judgment.
  5. At least one measurable disease tumour lesion by Response Evaluation Criteria in Solid
    Tumours Version 1.1 (RECIST v1.1) criteria.10 For suitable subjects, such as subjects that
    may not have measurable lesions, positron emission tomography (PET) may be implemented in addition to, or in place of, RECIST 1.1, to monitor disease response (PERCIST; PET response criteria in solid tumours version 1.0) on discussion and approval by the sponsor’s medical monitor.
  6. Subjects who have undergone treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody must have a gap of at least 4 weeks from the last dose of antibody and evidence of disease progression per the Investigator’s assessment before enrollment.
  7. Subjects who have previously received an immune CPI prior to enrollment must have any immune-related toxicities resolved to less than or equal to Grade 1 or baseline (prior to the CPI) with the exception of toxicities not considered a safety risk (eg, hypothyroidism, alopecia, neuropathy, or asymptomatic laboratory abnormalities).
  8. Adequate organ function based on laboratory assessments at Screening, as defined by:
    • Hemoglobin greater than or equal to 90 g/L (subjects may be transfused >2 weeks before Screening, but should not be transfusion-dependent).
    • Platelets greater than or equal to 100 × 109/L.
    • Absolute neutrophil count greater than or equal to 1.5 × 109/L.
    • Serum creatinine less than or equal to 1.5 × upper limit of normal (ULN); or a calculated creatinine clearance (Cockcroft-Gault method) greater than or equal to 50 mL/minute if serum creatinine >1.5 × ULN. Lower calculated creatinine clearance values may be allowed at the Investigator’s discretion and in consultation with the Medical Monitor and Sponsor.
    • Total bilirubin less than or equal to ULN; or conjugated bilirubin less than or equal to ULN and total bilirubin less than or equal to 1.5 × ULN (<3.0 × ULN for subjects with liver metastases or Gilbert’s syndrome).
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 × ULN (AST and ALT less than or equal to 5 × ULN if liver metastases present).
    • International normalized ratio and activated partial thromboplastin time less than or equal to 1.5 × ULN.
  9. For Part A, available archived tumor tissue sample (block of formalin-fixed paraffin-embedded [FFPE] tissues) to allow for exploratory biomarker studies. In the setting where archival material is unavailable or unsuitable for use (eg, recently diagnosed subjects or diagnosed with fine-needle aspiration), the subject will have an option to consent for and undergo fresh tumor biopsy (at acceptable risk as judged by the Investigator). The requirement for fresh biopsy collected from a given subject could be waived after the discussion with the Medical Monitor if the tumor tissues are not safely accessible as determined by the Investigator or the tumor biopsies have to be obtained from sites that require significant risk procedures.
  10. Female subjects must not be pregnant, or must be of non-childbearing potential; or if of childbearing potential, must agree to use highly effective birth control methods during the study treatment period and for at least 90 days after the last dose of the study treatment.
  11. Non-sterilized male subjects must agree to use contraception of this protocol during the treatment period and for at least 90 days after the last dose of the study treatment for Part A.
  12. For women of childbearing potential (WOCBP) only: A negative serum pregnancy test during Screening and a negative serum or urine pregnancy test within 24 hours of the first dose of study treatment.
  13. Voluntarily agrees to participate by giving written informed consent and is willing and able to comply with this protocol and scheduled visits.

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