Clinical Trials /

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

NCT04047290

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: AK112-101
  • NCT ID: NCT04047290

Conditions

  • Neoplasms Malignant

Interventions

DrugSynonymsArms
AK112AK112

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
AK112ExperimentalAK112 IV every 2 weeks (q2w)
  • AK112

Eligibility Criteria

        Inclusion Criteria:

          -  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. In
             the setting where archival material is unavailable or unsuitable for use, the subject
             must consent and undergo fresh tumor biopsy.

          -  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.

          -  Adequate life expectancy

        Exclusion Criteria:

          -  History of severe hypersensitivity reactions to other mAbs.

          -  For subjects enrolled in the dose escalation phase of the study (Phase 1a) who have
             received prior anti-PD-1, anti-PD-L1, anti-CTLA-4 or any other immunotherapy or
             immune-oncology (IO) agent:

               1. Subjects have received anti-PD-1, anti-PD-L1, anti-CTLA-4 or any other
                  immunotherapy or IO agent within 28 days of commencing treatment with
                  investigational product.

               2. Subjects have experienced a toxicity that led to permanent discontinuation of
                  prior immunotherapy. Subjects have experienced a ≥ Grade 3 irAE or a neurologic
                  or ocular AE of any grade while receiving prior immunotherapy.

               3. All AEs while receiving prior immunotherapy have not completely resolved or
                  resolved to Grade 1 prior to screening for this study.

               4. Subjects have required the use of additional immunosuppression other than
                  corticosteroids for the management of an AE, or have experienced recurrence of an
                  AE if re-challenged with corticosteroids while receiving prior immunotherapy.

          -  For dose-expansion phase (Phase 1b), prior exposure to any anti-PD-1, anti-PD-L1,
             anti-CTL4 antibody or any other antibody or drug targeting T-cell costimulation or
             checkpoint pathways such as ICOS, or agonists such as CD40, CD137, GITR, OX40 etc.

          -  Receipt of any immunotherapy, any conventional or investigational systemic anticancer
             therapy within 4 weeks prior to the first dose of AK112 except for treatment with
             small-molecule tyrosine kinase-targeted agents within 2 weeks prior to the first dose
             of AK112.

          -  Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer
             treatment. Concurrent use of hormones for non-cancer related conditions is acceptable.

          -  History or concurrent gastrointestinal perforation, surgery and wound healing
             complications, hemorrhage events.

          -  Subjects with clinically significant cardiovascular disease

          -  Subjects with a condition requiring systemic treatment with either corticosteroid (>
             10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
             days of study drug administration.

          -  Current or recent (within 10 days of the first dose of investigational product) use of
             aspirin (> 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and
             cilostazol.

          -  Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for
             therapeutic purposes that has not been stable for > 2 weeks prior to the first dose of
             AK112

          -  Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects
             with vitiligo, alopecia, Grave's disease, type I diabetes mellitus, hypothyroidism
             (e.g., following Hashimoto syndrome) only requiring hormone replacement on a stable
             dose, psoriasis or eczema not requiring systemic treatment (within the past 2 years),
             or conditions not expected to recur in the absence of an external trigger are not
             excluded.

          -  Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative
             colitis).

          -  History of primary immunodeficiency.

          -  History of organ transplant or hematopoietic stem cell that requires use of
             immunosuppressives.

          -  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, or to levels dictated in the inclusion/exclusion
             criteria.

          -  Major surgical procedure within 30 days prior to the first dose of AK112 or still
             recovering from prior surgery.

          -  Known history of tuberculosis.

          -  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. Subjects positive for HCV
             antibody are eligible only if quantitative HCV RNA results less than the lower limits
             of detection of the assay.

          -  An active infection requiring systemic therapy 25. with the exception of anti-viral
             therapy for hepatitis as specified by the protocol.

          -  Receipt of live attenuated vaccination within 30 days prior to the first dose of
             AK112.

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of the investigational product or interpretation of subject safety or study
             results.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events (AEs)
Time Frame:From time ICF is signed until 90 days after last dose of AK112
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
Measure:Disease control rate (DCR)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Progression-free survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:Overall survival is defined as the time from the start of treatment with AK112 until death due to any cause.
Measure:Area under the curve (AUC) of AK112
Time Frame:From first dose of AK112 through 90 days after last dose of AK112
Safety Issue:
Description:The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration.
Measure:Maximum observed concentration (Cmax) of AK112
Time Frame:From first dose of AK112 through 90 days after last dose of AK112
Safety Issue:
Description:The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration.
Measure:Minimum observed concentration (Cmin) of AK112 at steady state
Time Frame:From first dose of AK112 through 90 days after last dose of AK112
Safety Issue:
Description:The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration.
Measure:Number of subjects who develop detectable anti-drug antibodies (ADAs)
Time Frame:From first dose of AK112 through 90 days after last dose of AK112
Safety Issue:
Description:The immunogenicity of AK112 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Akesobio Australia Pty Ltd

Trial Keywords

  • anti-PD-1/VEGF bispecific antibody
  • immunotherapy
  • immuno-oncology
  • advanced solid tumors
  • bispecific
  • PD-1/VEGF

Last Updated

August 5, 2019