Advanced or Metastatic Solid TumorsPhase 1NCT04572152
A Study of AK119 (Anti-CD73) in Combination With AK104 in Subjects With Advanced Solid Tumors
A Phase 1 study testing AK119 and AK104 in people with Advanced or Metastatic Solid Tumors, run by Akeso at 5 sites in Australia.
Trial summary
This is a first-in-human (FIH), Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 (Anti-CD73) in Combination with AK104 in Subjects with Advanced or Metastatic Solid Tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Solid Tumors
- What is being tested?
- AK119 and AK104
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 5 sitesAustralia
- Study dates
- 7 Dec 2020to 31 Aug 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has provided written informed consent
- Age ≥ 18 years.
- In dose-escalation cohorts (Phase 1a), subjects must have histologically or cytologically confirmed advanced or metastatic solid tumor that is refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available, or whereby standard therapy has been refused.
- In pharmacodynamic-confirmation cohorts (Phase 1a), additional enrolled subjects must have histologically or cytologically confirmed selected advanced or metastatic solid tumors, refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available. Other tumor types can be considered after discussion with the Sponsor.
- In dose-expansion cohorts (Phase 1b), subjects with specific tumor types will be enrolled. Subjects must have received no more than three prior lines of systemic therapy (including approved and investigational treatments) for advanced or metastatic disease. Other cohorts of different tumor types may be added based on the emerging pharmacodynamic and anti-tumor response data.
- Subjects must have measurable lesions according to RECIST v1.1. A previously irradiated lesion can be considered a target lesion if the lesion is measurable per RECIST v1.1, and there is objective evidence of interval increase in size since radiotherapy.
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- For dose-escalation cohorts (Phase 1a), subjects must have available archived tumor tissue sample (block or a minimum of 10 unstained slides of formalin-fixed paraffin-embedded [FFPE] tissues) to allow for correlative biomarker studies.
- For pharmacodynamic-confirmation cohorts (Phase 1a) and dose-expansion cohorts (Phase 1b), subjects must be willing to provide 2 fresh biopsy samples (pre-treatment and on treatment), where clinically appropriate.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to1.
- Adequate organ function
- Life expectancy ≥12 weeks;
- Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and within 120 days after the last dose of investigational product.
- Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and within 120 days after the last dose of investigational product.
Who cannot join
- Receipt of the following treatments or procedures:
- Anticancer small-molecule targeted agent (e.g., tyrosine kinase inhibitor) within 2 weeks prior to the first dose of investigational product;
- Anti-PD-1/PD-L1 mAb within 4 weeks prior to the first dose of investigational product;
- Prior use of approved or investigational anti-CTLA-4 therapy, anti-CD73 therapy or adenosine 2A receptor inhibitors, or any other antibody or drug targeting T cell costimulation or immune checkpoint pathways such as ICOS, or agonists such as CD40, CD137, GITR, OX40 etc.
- Other anticancer mAb within 4 weeks or 5 half-lives (whichever is less) prior to the first dose of investigational product;
- Other anticancer therapy (e.g., chemotherapy, radiotherapy, etc.) within 4 weeks prior to the first dose of investigational product; [Note: Palliative radiotherapy > 1 week prior to first dose is allowed]
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- Any major surgery (e.g., laparotomy, thoracotomy, removal of organ[s]) within 4 weeks prior to the first dose of investigational product;
- Any other non-approved investigational product or procedure within 4 weeks prior to the first dose of investigational product, or concurrent participation in another therapeutic clinical study;
- Any condition that required systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of investigational product.
- Receipt of live attenuated vaccines within 4 weeks prior to the first dose of investigational product; Note: seasonal vaccine for influenza which is generally inactivated is allowed.
- Prior organ transplantation;
- Prior malignancy active within the previous 3 years except for the tumor for which a subject is enrolled in the study, and locally curable cancers that have been apparently cured, such as basal cell cancer or carcinoma in situ of the cervix or breast;
- Subjects with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at Screening (based on 2 sets of brain images, performed ≥ 4 weeks apart, and obtained after the brain metastases treatment).
- Active infections (including tuberculosis) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to the first dose of investigational products. Note: antiviral therapy is permitted for patients with viral hepatitis;
- Known history of human immunodeficiency virus (HIV) infection;
- Known active hepatitis B or C infections (Active hepatitis B is defined as a known positive Hepatitis B surface antigen [HBsAg] result. Active hepatitis C is defined by a known positive Hepatitis C virus [HCV] antibody with detectable HCV ribonucleic acid [RNA] results);
- Active autoimmune diseases or history of autoimmune diseases that may relapse. Note: Subjects with controlled type 1 diabetes mellitus, thyroiditis in euthyroid state or hypothyroidism well managed by hormone replacement therapy (HRT), or skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis) are eligible;
- History of interstitial lung disease, noninfectious pneumonitis except for those induced by radiation therapies;
- Uncontrolled massive ascites or pleural effusion, as determined by the Investigator;
- Patients with clinically significant cardio-cerebrovascular or venous thromboembolic disease.
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec calculated from 3 ECGs (within 5 minutes at least 1 minute apart);
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, uncontrolled diabetes, uncontrolled endocrinopathy, severe active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent;
- History of severe hypersensitivity reactions to other mAbs;
- Toxicities of prior anticancer therapy have not resolved to NCI-CTCAE version 5.0 Grade ≤1, or to levels dictated in the inclusion/exclusion criteria, except toxicities not considered a safety risk (e.g., alopecia, neuropathy, or asymptomatic laboratory abnormalities);
- Pregnant or breastfeeding women;
- Any other conditions that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Australia5 sites
Ashford Cancer Centre
Adelaide, South Australia, 5037
Blacktown Cancer and Haematology Centre (Blacktown Hospital)
Blacktown, New South Wales, 2148
Monash Health
Clayton, Victoria, 3168
Alfred Health (The Alfred Hospital)
Melbourne, Victoria, 3004
ICON Cancer Centre
South Brisbane, Queensland, 4101
About this study
Official title: A Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 in Combination With AK104 in Subjects With Advanced or Metastatic Solid Tumors.
This is a first-in-human (FIH), Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 (Anti-CD73) in Combination with AK104 in Subjects with Advanced or Metastatic Solid Tumors.
- Conditions
- Advanced or Metastatic Solid Tumors
- Being tested
- AK119, AK104
- Keywords
- Anti CD73, PD-1/ CTLA-4, Bispecific
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK119Biological
Subjects will receive AK119 by intravenous administration.
AK104Biological
On the same day subjects will receive AK104 by intravenous administration.
| Study group | Role | What they receive |
|---|---|---|
| AK119/ AK104 | Experimental | Single-arm Receives: Biological: AK119; Biological: AK104 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measured: From the time of informed consent signed through 90 days after the last dose of study drug
Number of participants with a Dose Limiting Toxicity (DLT)
DLTs will be assessed during the first 6 weeks of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 6 weeks of treatment.
Measured: During the first 6 weeks
Secondary outcomes (5)
Objective response rate (ORR)
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1
Measured: Up to 2 years
Disease control rate (DCR)
The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
Measured: Up to 2 years
Maximum observed concentration (Cmax) of AK119 and AK104
The endpoints for assessment of PK include serum concentrations of AK119 and AK104 at different timepoints after study drug administration.
Measured: From first dose of study drug through 30 days after last dose of study drug
Minimum observed concentration (Cmin) of AK119 and AK104 at steady state
The endpoints for assessment of PK include serum concentrations of AK119 and AK104 at different timepoints after study drug administration.
Measured: From first dose of study drug through 30 days after last dose of study drug
Number of subjects who develop detectable anti-drug antibodies (ADAs)
The immunogenicity of AK119 and AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).
Measured: From first dose of study drug through 90 days after last dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2020
- Study start7 Dec 2020
- Primary completion2 May 2023
- Study completion31 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Solid TumorsStudies of the same condition, open and under way.
- More trials run by AkesoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akeso
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04572152
- Sponsor's protocol ID
- AK119-102
- Status last verified
- Feb 2025
- First submitted
- 27 Sep 2020
- Last updated
- 28 Feb 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 in Combination With AK104 in Subjects With Advanced or Metastatic Solid Tumors.
- ClinicalTrials.gov ID
- NCT04572152
- Acronym / sponsor ID
- AK119-102
- Conditions
- Advanced or Metastatic Solid Tumors
- Keywords
- Anti CD73, PD-1/ CTLA-4, Bispecific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- AkesoIndustry (pharma, biotech, devices)
- Study start
- 7 Dec 2020 (actual)
- Primary completion
- 2 May 2023 (actual)
- Study completion
- 31 Aug 2023 (actual)
- First posted
- 1 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a first-in-human (FIH), Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 (Anti-CD73) in Combination with AK104 in Subjects with Advanced or Metastatic Solid Tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AK119/ AK104 | Experimental | Biological: AK119, Biological: AK104Single-arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Has provided written informed consent
- Age ≥ 18 years.
- In dose-escalation cohorts (Phase 1a), subjects must have histologically or cytologically confirmed advanced or metastatic solid tumor that is refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available, or whereby standard therapy has been refused.
- In pharmacodynamic-confirmation cohorts (Phase 1a), additional enrolled subjects must have histologically or cytologically confirmed selected advanced or metastatic solid tumors, refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available. Other tumor types can be considered after discussion with the Sponsor.
- In dose-expansion cohorts (Phase 1b), subjects with specific tumor types will be enrolled. Subjects must have received no more than three prior lines of systemic therapy (including approved and investigational treatments) for advanced or metastatic disease. Other cohorts of different tumor types may be added based on the emerging pharmacodynamic and anti-tumor response data.
Key exclusion criteria (26 listed)
- Receipt of the following treatments or procedures:
- Any condition that required systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of investigational product.
- Receipt of live attenuated vaccines within 4 weeks prior to the first dose of investigational product; Note: seasonal vaccine for influenza which is generally inactivated is allowed.
- Prior organ transplantation;
- Prior malignancy active within the previous 3 years except for the tumor for which a subject is enrolled in the study, and locally curable cancers that have been apparently cured, such as basal cell cancer or carcinoma in situ of the cervix or breast;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AK119Subjects will receive AK119 by intravenous administration. | Biological | AK119/ AK104 |
| AK104On the same day subjects will receive AK104 by intravenous administration. | Biological | AK119/ AK104 |
Primary outcome
Number of participants with adverse events (AEs)
Time frame: From the time of informed consent signed through 90 days after the last dose of study drug
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Number of participants with a Dose Limiting Toxicity (DLT)
Time frame: During the first 6 weeks
DLTs will be assessed during the first 6 weeks of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 6 weeks of treatment.
5 secondary outcomes
Objective response rate (ORR)
Time frame: Up to 2 years
Disease control rate (DCR)
Time frame: Up to 2 years
Maximum observed concentration (Cmax) of AK119 and AK104
Time frame: From first dose of study drug through 30 days after last dose of study drug
Minimum observed concentration (Cmin) of AK119 and AK104 at steady state
Time frame: From first dose of study drug through 30 days after last dose of study drug
Number of subjects who develop detectable anti-drug antibodies (ADAs)
Time frame: From first dose of study drug through 90 days after last dose of study drug
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AK119 and AK104 in people with Advanced or Metastatic Solid Tumors, run by Akeso at 5 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (AEs) (time frame: From the time of informed consent signed through 90 days after the last dose of study drug). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.