Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000863437
Ethics application status
Approved
Date submitted
19/05/2025
Date registered
8/08/2025
Date last updated
8/08/2025
Date data sharing statement initially provided
8/08/2025
Type of registration
Retrospectively registered

Titles & IDs
Public title
A first-in-human study evaluating the safety of AXA-042 in combination with an anti-PD-1 monoclonal antibody (cemiplimab) in patients with advanced solid tumors.
Scientific title
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 1b
Secondary ID [1] 314098 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
This registration is for Part B of the same study. Registration record ACTRN12622000993796 is for Part A of the study.

Health condition
Health condition(s) or problem(s) studied:
Advanced solid tumours 337485 0
Condition category
Condition code
Cancer 333851 333851 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 331069 0
Treatment: Drugs
Comparator / control treatment
No control group. This is an open label study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 341466 0
Determine the incidence of Adverse Events and Dose-limiting toxicities related to AXA-042 administered as a combination therapy with cemiplimab, due to immune activation including cytokine release, joint inflammation and infusion-related reactions.
Timepoint [1] 341466 0
All adverse events will be collected from the start of the study treatment (Cycle 1 Day 1) until the End of Treatment (EOT) visit. The EOT visit will occur within 7 days of the decision to cease treatment or the day before the start of any new anti-cancer treatment. If study treatment is discontinued due to AEs, the EOT visit may occur beyond 90 days or 1 day before subject receives their first dose of new anti-cancer systemic therapy, whichever is earlier. Subjects who discontinue study treatment will enter the survival follow up period and return to the site every 12 weeks until the End of Study (EOS). Vital signs will be taken at every site visit throughout treatment. For all cycles, on Day 1, vital sign measurements will be performed within 30 minutes before AXA-042 infusion, then every 15 minutes until the end of infusion (EOI), and at 30 minutes, 1 h, and 2 h after EOI. Additional assessments will be conducted at 4 h and 6 h post-EOI on Cycle 1 Day 1 and Cycle 2 Day 1 (cemiplimab initiation). On other specified days, a single assessment will be performed. Vital signs include systolic and diastolic blood pressure, respiratory rate, pulse rate, and body temperature (tympanic). Blood pressure and pulse rate will be assessed using a completely automated device; manual techniques will be used only if an automated device is not available. ECG assessments will be performed on Day 1 of every cycle and at the EOT visit. For all cycles, ECG assessments will be performed within 60 minutes before dosing and again at 4 h post-EOI. At the EOT visit, a single ECG will be performed. Eastern Cooperative Oncology Group (ECOG) performance status will be assessed during screening and within 2 hours of pre-dose on Day 1 Cycle 2, Day 1 Cycle 3, and every other cycle thereafter, as well as at the EOT visit. Physical examinations will be conducted during screening, within 2 hours of pre-dose on Day 1 of Cycle 1, and during visits on Day 8 and Day 15 of Cycle 1 and Cycle 2, and on Day 1 of subsequent cycles and the EOT visit. Laboratory assessments will be performed at screening, Day 1, Day 2, Day 8, and Day 15 of Cycle 1 and Cycle 2, and on Day 1 for subsequent cycles and at the EOT visit. For all cycles, samples for safety laboratory tests will be collected prior to dosing on Day 1. Blood samples will be collected as scheduled to assess blood counts, liver function, renal function, coagulation factors, and thyroid function. Urine will be collected for urinalysis at screening, Day 1, Day 2, Day 8, and Day 15 of Cycles 1, 2 and 3, and at the EOT visit.
Secondary outcome [1] 447630 0
Concentrations of AXA-042 in plasma when administered in combination with cemiplimab, including the concentration–time profile and PK parameters such as AUC0-336h, AUC0-504h, AUC0-last, AUC0-inf, t½, MRT in vivo, Vd, CL, Cmax and tmax.
Timepoint [1] 447630 0
Determine the pharmacokinetics (PK) of AXA-042 in plasma when administered intravenously in combination with cemiplimab on Day 1 of a 21-day cycle, including: Cycle 1 Day 1: pre-dose and post-dose at 0.25, 1, 2, 4, and 6 hours; Cycle 1 Day 2 (24h), Day 8 (168h), and Day 15 (336h) post-dose.
Secondary outcome [2] 447632 0
Incidence of immunogenicity (ADA) against AXA-042 in serum, when used as combination therapy with cemiplimab.
Timepoint [2] 447632 0
ADA will be assessed pre-dose on Day 1 of each cycle. There is no maximum number of cycles; samples will be collected until end of treatment.
Secondary outcome [3] 447633 0
Pharmacodynamic (PD) parameters evaluated in blood including cytokines and immune-related gene expression.
Timepoint [3] 447633 0
PD markers will be assessed on: • Cycle 1 Day 1 pre-dose and 1hour and 4 hours post dose; Day 2 and Day 15 at any time during the visit • Cycle 2 Day 1 pre-dose, 1 hour and 4 hours post-dose; Day 2 anytime during the visit • Cycle 3 Day 1, pre-dose and 4 hours post-dose, Day 2 and Day 15 • Cycle 4 and every odd cycle after Cycle 4: Day 1, pre-dose and 4 hours post-dose.
Secondary outcome [4] 447634 0
Tumour response assessed using Response Evaluation Criteria in Solid Tumours v1.1.
Timepoint [4] 447634 0
Tumour assessments will be conducted at screening and at every 4th Cycle on Day 1 (i.e. Cycle 4 Day 1, Cycle 8 Day 1).
Secondary outcome [5] 447635 0
Quality of Life (QoL) assessment using a validated questionnaire.
Timepoint [5] 447635 0
QoL parameters will be assessed at screening and at every 4th Cycle on Day 1 (i.e. Cycle 4 Day 1, Cycle 8 Day 1).
Secondary outcome [6] 450325 0
Pharmacodynamic (PD) parameters evaluated in tumour tissue including histology, gene expression and target engagement biomarkers.
Timepoint [6] 450325 0
Screening (pre-dose) and on Cycle 1 Day 15.
Secondary outcome [7] 450326 0
Tumour response to be assessed using iRECIST - immune-modified RECIST (Response Evaluation Criteria in Solid Tumours).
Timepoint [7] 450326 0
Tumour assessments will be conducted at screening and at every 4th Cycle on Day 1 (i.e. Cycle 4 Day 1, Cycle 8 Day 1).
Secondary outcome [8] 450327 0
Tumour response will be assessed using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST).
Timepoint [8] 450327 0
Tumour assessments will be conducted at screening and at every 4th Cycle on Day 1 (i.e. Cycle 4 Day 1, Cycle 8 Day 1).

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Given the exploratory nature of this study, the sample size is not based on formal statistical considerations. The sample size will depend on the number of dose levels evaluated in the study. Additional subjects may be enrolled based on the emerging safety and PK data from this study.
All analyses, summaries, and listings will be performed using SAS software (version 9.4 or higher). In general, data will be presented by AXA-042 dose level groups. Data for all study subjects combined will also be presented. Individual subject data will be presented in listings. Data will be summarized using descriptive statistics (mean, median, standard deviation, minimum and maximum) or frequency counts and percentages, as appropriate to the type of data.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
23/01/2025
Date of last participant enrolment
Anticipated
30/04/2026
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
12
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 27949 0
Linear Clinical Research - Nedlands
Recruitment hospital [2] 27950 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 27953 0
Dandenong Hospital- Monash Health - Dandenong
Recruitment hospital [4] 27954 0
Scientia Clinical Research - Randwick
Recruitment hospital [5] 27955 0
Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [6] 27956 0
Calvary Mater Newcastle - Waratah
Recruitment postcode(s) [1] 44142 0
6009 - Nedlands
Recruitment postcode(s) [2] 44143 0
3000 - Melbourne
Recruitment postcode(s) [3] 44145 0
3175 - Dandenong
Recruitment postcode(s) [4] 44146 0
2031 - Randwick
Recruitment postcode(s) [5] 44147 0
2050 - Camperdown
Recruitment postcode(s) [6] 44148 0
2298 - Waratah

Funding & Sponsors
Funding source category [1] 318606 0
Commercial sector/Industry
Name [1] 318606 0
Axelia Oncology Pty Ltd
Country [1] 318606 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Axelia Oncology Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 321009 0
None
Name [1] 321009 0
Address [1] 321009 0
Country [1] 321009 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317209 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 317209 0
Ethics committee country [1] 317209 0
Australia
Date submitted for ethics approval [1] 317209 0
19/12/2023
Approval date [1] 317209 0
03/01/2024
Ethics approval number [1] 317209 0
Ethics committee name [2] 317589 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [2] 317589 0
Ethics committee country [2] 317589 0
Australia
Date submitted for ethics approval [2] 317589 0
08/03/2024
Approval date [2] 317589 0
30/04/2024
Ethics approval number [2] 317589 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 140350 0
Prof Michael Millward
Address 140350 0
Ground Floor, B block, QEII Medical Centre, Hospital Avenue, Nedlands WA 6009
Country 140350 0
Australia
Phone 140350 0
+61 8 6373 6201
Fax 140350 0
Email 140350 0
[email protected]
Contact person for public queries
Name 140351 0
Ardian Latifi
Address 140351 0
Axelia Oncology, 31 Queen Street, Melbourne VIC 3000
Country 140351 0
Australia
Phone 140351 0
+61 421814712
Fax 140351 0
Email 140351 0
[email protected]
Contact person for scientific queries
Name 140352 0
Phil Kearney
Address 140352 0
Axelia Oncology, 31 Queen Street, Melbourne VIC 3000
Country 140352 0
Australia
Phone 140352 0
+61 414795133
Fax 140352 0
Email 140352 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.