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Neoplasms MalignantPhase 1NCT04047290

A Study of AK112, a PD-1/VEGF Bispecific Antibody, for Advanced Solid Tumors

A Phase 1 study testing AK112 in people with Neoplasms Malignant, run by Akesobio Australia Pty Ltd at 7 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK112, a PD-1/VEGF bispecific antibody, as a single agent in adult subjects with advanced solid tumor malignancies. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms Malignant
What is being tested?
AK112
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
7 sitesAustralia
Study dates
20 Sep 2019to 27 Feb 2024
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

  • Written and signed informed consent and any locally required authorization obtained from the subject/legal representative.
  • In dose-escalation cohorts (Phase 1a), histologically or cytologically documented advanced or metastatic solid tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject refuses standard therapy.
  • In the dose-expansion cohorts (Phase 1b), histologically or cytologically confirmed selected advanced solid tumors.
  • Subject must have at least one measurable lesion according to RECIST Version1.1.
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
  • Available archived tumor tissue sample to allow for correlative biomarker studies. If unavailable or unsuitable, the subject must consent and undergo fresh tumor biopsy.
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  • Adequate organ function.
  • Subjects with central nervous system (CNS) metastases must have been treated, be asymptomatic.
  • Females of childbearing potential and non-sterilized males who are sexually active must use an effective method of contraception from screening until 120 days after final dose of investigational product or women of non child bearing potential.
  • Life expectancy ≥12 weeks.

Who cannot join

  • History of severe hypersensitivity reactions to other mAbs.
  • 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, (e.g. basal cell skin cancer, or carcinoma in situ of the cervix or breast).
  • For subjects enrolled in the dose escalation phase, having received prior anti-PD-1, anti-PD-L1, anti-CTLA-4 or any other immunotherapy or immune-oncology (IO) agent within 28 days of commencing treatment with AK112 or experienced a toxicity that led to permanent discontinuation of prior immunotherapy. All AEs while receiving prior immunotherapy have not completely resolved or resolved to Grade 1 prior to screening, required the use of additional immunosuppression other than corticosteroids
  • Receiving any immunotherapy, conventional or investigational systemic anticancer therapy within 4 weeks prior to the first dose
  • Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment (hormones use for non-cancer related conditions is acceptable).
  • Subjects with clinically significant cardiovascular disease
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  • Subjects with a condition requiring systemic treatment with either corticosteroid (> 10 mg daily ) or other immunosuppressive medications within 2 weeks of study drug administration.
  • Current or recent use of aspirin (> 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol.
  • Current unstable of full-dose oral or parenteral anticoagulants or thrombolytic agents for > 2 weeks prior to the first dose of AK112
  • Active or prior documented autoimmune disease within the past 2 years or conditions not expected to recur in the absence of an external trigger)
  • Active or prior documented inflammatory bowel disease
  • History of primary immunodeficiency.
  • History of organ transplant.
  • Known allergy or reaction to any component of the AK112 formulation.
  • History of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.
  • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade 0 or 1
  • Major surgical procedure within 30 days prior to the first dose of AK112 or still recovering from prior surgery.
  • Known history of HIV.
  • Known active hepatitis B or C infections. Note: Subjects with HCC and positive HBsAg result are eligible if the subjects were treated with antiviral therapy and HBV viral load less than 500 IU/mL prior to first dose of AK112.
  • An active infection requiring systemic therapy
  • Received live attenuated vaccination within 30 days prior to the first dose of AK112.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Australia7 sites

  • Border Medical Oncology

    Albury, New South Wales

  • Monash Health

    Clayton, Victoria

  • Adelaide Cancer Centre

    Kurralta Park, South Australia

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria

  • Scientia Clinical Research Ltd

    Randwick, New South Wales

  • ICON Cancer Foundation

    South Brisbane, Queensland

  • Blacktown Hospital

    Sydney, New South Wales

Other trials in Australia

About this study

Official title: A Phase 1a/1b, Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK112 in Subjects With Advanced Solid Tumors

This study is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK112, a PD-1/VEGF bispecific antibody, as a single agent in adult subjects with advanced solid tumor malignancies. The study consists of a dose escalation phase (Phase 1a) to determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D) for AK112 as a single agent, and a dose expansion phase (Phase 1b) in subjects with specific tumor types which will characterize treatment of AK112 as a single agent at the MTD or RP2D.

Being tested
AK112
Keywords
anti-PD-1/VEGF bispecific antibody, immunotherapy, immuno-oncology, advanced solid tumors, bispecific, PD-1/VEGF
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AK112Drug

    AK112 is a PD1/VEGF bispecific antibody.

Study groups in NCT04047290
Study groupRoleWhat they receive
AK112ExperimentalAK112 IV every 2 weeks (q2w) or every 3 weeks (q3w)
Receives: Drug: AK112

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence and nature 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 time ICF is signed until 90 days after last dose of AK112

  2. Number of participants with DLTs

    DLTs will be assessed during the 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, intercurrent illness, or concomitant medications that occurs within the first cycle (4 weeks) of treatment.

    Measured: During the first four weeks of treatment with AK112

Secondary outcomes (7)

  1. 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

  2. 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 at 16 and 24 weeks respectively) based on RECIST Version 1.1.

    Measured: Up to 2 years

  3. Progression-free survival (PFS)

    Progression-free survival is defined as the time from the start of treatment with AK112 until the first documentation of disease progression or death due to any cause, whichever occurs first.

    Measured: Up to 2 years

  4. Overall survival (OS)

    Overall survival is defined as the time from the start of treatment with AK112 until death due to any cause.

    Measured: Up to 2 years

  5. Area under the curve (AUC) of AK112 for assessment of pharmacokinetics

    The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration.

    Measured: From first dose of AK112 through 90 days after last dose of AK112

  6. Maximum observed concentration (Cmax) and Minimum observed concentration (Cmin) of AK112

    The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration.

    Measured: From first dose of AK112 through 90 days after last dose of AK112

  7. Number of subjects who develop detectable anti-drug antibodies (ADAs)

    The immunogenicity of AK112 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

    Measured: From first dose of AK112 through 90 days after last dose of AK112

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2019
  2. Study start20 Sep 2019
  3. Primary completion27 Feb 2024
  4. Study completion27 Feb 2024

Resources

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
Model description
Sequential Assignment Initially, a single-subject cohort will be enrolled at the protocol starting dose of AK112 every 2 weeks (Q2W). Dose escalation will proceed to the next main dose level according to the 3+3+3 dose-escalation procedure until the MTD is reached. Dose expansion phase of the study will be initiated at the Sponsor's discretion at the dose level and treatment schedule which was established as the recommended Phase 2 dose (RP2D) in the dose-escalation phase.
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04047290
Sponsor's protocol ID
AK112-101
Status last verified
Feb 2025
First submitted
5 Aug 2019
Last updated
28 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Frentzas S, Austria Mislang AR, Lemech C, Nagrial A, Underhill C, Wang W, Wang ZM, Li B, Xia Y, Coward JIG. Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors. J Immunother Cancer. 2024 Apr 19;12(4):e008037. doi: 10.1136/jitc-2023-008037.

    PubMed 38642937

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AK112 in people with Neoplasms Malignant, run by Akesobio Australia Pty Ltd at 7 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 10 inclusion and 21 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 7 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?

Incidence and nature of participants with adverse events (AEs) (time frame: From time ICF is signed until 90 days after last dose of AK112). 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?

On the ClinicalTrials.gov record for NCT04047290, which also lists 1 linked publication.

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.

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