None listed
Conditions
Brief summary
AXA-042 furnctions 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 in combination with cemiplimab, an anti-PD-1 monoclonal antibody, in subjects with advanced solid tumours. Who is it for ? You may be eligible for this study if you are aged 18 years or over, have a diagnosis of a locally advanced or metastatic solid tumor, and are refractory or intolerant to standard of care therapies. Study details – Participants will receive AXA-042 followed by cemiplimab, both administered as intravenous infusions on Day 1 of a 21-day treatment cycle. AXA-042 will be given first; if no significant infusion-related reaction occurs within one hour, cemiplimab will follow. Treatment will continue until disease progression, withdrawal of consent, or toxicity that in the opinion of the investigator or Sponsor requires study treatment discontinuation, or up to study completion, whichever occurs first. Dose escalation will follow a 3+3 design, where 3 to 6 participants will be enrolled per cohort to evaluate safety and determine the maximum tolerated dose. The starting dose level of AXA-042 is 0.00001 mg/kg, and all doses of cemiplimab are fixed at 350 mg IV every 3 weeks. The dose of AXA-042 will be increased by up to 3-fold in each subsequent cohort, after review of safety data, to determine the maximum tolerated dose. Participants will be monitored for adverse events throughout treatment and for at least 30 days after their last dose. of study drug. Participants will also have blood samples taken throughout day 1 (and in subsequent cycles on certain days) of treatment after receiving AXA-042 to study the time course of drug absorption, distribution, metabolism and excretion. Preliminary efficacy and pharmacodynamics will be determined through objective response rate, progression-free survival, time to response and overall survival and pharmacodynamics data on cytokines and other immune response biomarkers in response to AXA-042 treatment (in combination with cemiplimab). It is hoped that this study may show that AXA-042, in combination with cemiplimab, is safe and effective for the treatment of advanced solid tumours, which may lead the way for larger efficacy trials in future.
Interventions
The study will evaluate ascending doses of AXA-042 in combination with cemiplimab to investigate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy in patients with advanced solid tumors.
After Screening, all eligible subjects will be enrolled to receive AXA-042 during Cycle 1, undergo another biopsy at Day 15, followed by the combination treatment with AXA-042 and cemiplimab from Cycle 2 and onwards. AXA-042 and cemiplimab will be administered as sequential i
The study will evaluate ascending doses of AXA-042 in combination with cemiplimab to investigate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy in patients with advanced solid tumors. After Screening, all eligible subjects will be enrolled to receive AXA-042 during Cycle 1, undergo another biopsy at Day 15, followed by the combination treatment with AXA-042 and cemiplimab from Cycle 2 and onwards. AXA-042 and cemiplimab will be administered as sequential intravenous infusions once every 21 days (Day 1 of each treatment cycle). AXA-042 treatment will be delivered first, and subjects who do not experience any infusion-related reactions (IRRs) within 1 hour of receiving AXA-042 will then receive cemiplimab thereafter. The starting dose level of AXA-042 has been determined from the safety, PK, and PD data from Part A of the study (ACTRN12622000993796), and is 0.0001 mg/kg (7 µg for a 70 kg human) of AXA-042. All dose levels of cemiplimab are fixed at 350 mg intravenously every 3 weeks. Dose escalation will follow a standard 3+3 design. Approximately 10 to 12 patients are expected to be enrolled in up to 3 dose cohorts. The maximum dose to be tested is 0.0003 mg/kg, which has been determined following evaluation of the safety, PK and PD data from part A of the study. A new cohort of participants will be enrolled in Part B of the study. Intrasubject dose escalation is permitted if the subject is tolerating their initial dose, the higher dose cohort has completed the dose-limiting toxicity (DLT) period (Cycle 2 Day 1 to Day 21) without evidence of DLT, and the dose has been declared safe by the Safety Monitoring Committee. Escalation of up to two dose levels is permitted for individual patients at the discretion of the Principal Investigator and Medical Monitor. If the combination of AXA-042 and cemiplimab is found to be safe and tolerable, study treatment will continue until disease progression, withdrawal of consent, discontinuation due to toxicity, or other reasons deemed appropriate by the Investigator or Sponsor.
Sponsors
Axelia Oncology Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Healthy volunteers
No
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. Fresh tumour biopsies collected (at acceptable risk as judged by the Investigator) at Screening and on Cycle 1 Day 15 . 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 4 months 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 4 months after the last dose of the study treatment. 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.
Exclusion criteria
1. Subjects diagnosed with glioblastoma, other brain tumors, and hematological cancer. In the case of rare cancers, there may be some exceptions at the Investigator’s discretion in consultation with the Medical Monitor. 2. Prior malignancies active within previous 3 years, except the cancer for which the subject is enrolled in the current study or locally curable cancers that have been cured (eg, basal cell skin cancer, squamous cell carcinoma, or carcinoma in situ of the cervix or breast). 3. Known active central nervous system metastases or carcinomatous meningitis. 4. Active or documented history of autoimmune disease that has caused terminal organ damage or required systemic immunosuppression and/or systemic disease modulating drugs within the past 2 years, or participant is immunocompromised for any other reason. Subjects with active or document history of autoimmune disease that has caused terminal organ damage or required systemic immunosuppression and/or systemic disease modulating drugs within the past 2 years or participant is immunocompromised for any other reason may be allowed on case-by-case basis with the approval of the study Sponsor if it is deemed not to put subject at an increased risk of treatment-related toxicities and/or interfere with study data integrity, e.g., hypothyroidism on adequate thyroid hormone replacement therapy. 5. Active or a history of clinically significant atopy (severe or multiple allergic manifestations). Subjects with asthma requiring the administration of regular inhaled steroids, or a history of asthma requiring hospitalisation will be excluded. Note that subjects with active mild asthma requiring intermittent bronchodilator administration and/or short-term inhaled steroids may be allowed on Medical Monitor/Sponsor approval. 6. Current or known history of rheumatoid arthritis, ankylosing spondylitis, or any other joint inflammatory conditions that have systemic and/or organ involvement, and/or involve disease flares affecting joint function. Osteoarthritis alone is not exclusionary. For uncertain cases, final determination can be made as per the discretion of the PI in consultation with the Medical Monitor. 7. Active systemic infection requiring treatment with intravenous antibiotics or a significant infection (minor superficial skin infections or urinary tract infections are not exclusionary). 8. History of a severe hypersensitivity reaction. 9. History of recurrent or clinically significant syncope. 10. Have uncontrolled pleural effusion(s), pericardial effusion, or ascites. 11. Evidence of abnormal cardiac function as defined by any of the following: • Myocardial infarction within 6 months of Cycle 1 Day 1. • Symptomatic congestive heart failure (New York Heart Association Class II or greater). • Unstable angina. 12. Received chemotherapy, or other anticancer therapy within 4 weeks prior to the first dose of study treatment. Exceptions include concurrent standard of care (SOC) therapies such as the use of hormones for noncancer-related conditions (e.g., insulin for diabetes), hormone deprivation therapy (e.g., androgen deprivation therapy for prostate cancer), antiresorptive therapy (e.g., bisphosphonates, denosumab for prevention of osteoporosis, bone disease etc.), and local treatment of isolated lesions for palliative intent (e.g., by local surgery or local radiotherapy). Subjects on SOC therapy are required to be on a stable dose for a period of at least 1 month prior to enrolment without any foreseeable changes in dose during the duration of this trial. Palliative subjects who have received radiotherapy treatment are allowed after 7 days of their last treatment. Any other concurrent SOC therapies not included here are to be discussed and approved by the MM prior to screening of the subject 13. Received prior TLR agonist therapy. 14. Currently taking chronic systemic glucocorticoid therapy in excess of replacement doses (ie, >10 mg prednisone/day or equivalent) or other systemic immunosuppressive treatment. 15. Have undergone major surgery in the 4 weeks prior to Screening or minor surgical procedures less than or equal to 7 days (no waiting required following port-a-cath placement or for venous access). For any minor surgical procedures related to the biopsy collection, a more than 7 days washout will suffice. 16. Received investigational therapy or used an investigational device within 4 weeks prior to the first dose of study treatment. 17. Received a live vaccine within 30 days prior to the first dose of study treatment. 18. Pregnant or breastfeeding or expecting to conceive a child during the study or within 4 months after the last dose of study treatment. 19. Known history of human immunodeficiency virus infection or active infection with hepatitis B or C. 20. Have a psychiatric or substance use disorder that would interfere with cooperation with the requirements of the study. 21. History of any condition or treatment which could confound the results of the study, interfere with the subject’s participation in the study, or make study participation not in the subject’s best interests, in the opinion of the Investigator. 22. Hypersensitivity to cemiplimab or any of its excipients or contraindicated to cemiplimab per approved local labelling. 23. History of greater than or equal to Grade 2 hypertension. Exception can be made based on Medical Monitor approval if BP increase is transient due to other reasons like the white coat syndrome.
Outcome results
None listed