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History of Changes for Study: NCT04047290
A Study of AK112, a PD-1/VEGF Bispecific Antibody, for Advanced Solid Tumors
Latest version (submitted June 21, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 5, 2019 None (earliest Version on record)
2 December 28, 2021 Recruitment Status, Contacts/Locations, Study Status, Outcome Measures, Study Design, Eligibility, Arms and Interventions and Oversight
3 June 21, 2022 Contacts/Locations and Study Status
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Study NCT04047290
Submitted Date:  August 5, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: AK112-101
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
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2019
Overall Status: Not yet recruiting
Study Start: August 15, 2019
Primary Completion: August 30, 2022 [Anticipated]
Study Completion: December 30, 2022 [Anticipated]
First Submitted: August 5, 2019
First Submitted that
Met QC Criteria:
August 5, 2019
First Posted: August 6, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
August 5, 2019
Last Update Posted: August 6, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Akesobio Australia Pty Ltd
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief 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. 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.
Detailed Description:
Open or close this module Conditions
Conditions: Neoplasms Malignant
Keywords: anti-PD-1/VEGF bispecific antibody
immunotherapy
immuno-oncology
advanced solid tumors
bispecific
PD-1/VEGF
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 132 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: AK112
AK112 IV every 2 weeks (q2w)
Drug: AK112
AK112 is a PD1/VEGF bispecific antibody.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Number of participants with adverse events (AEs)
[ Time Frame: From time ICF is signed until 90 days after last dose of AK112 ]

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.
2. Number of participants with DLTs
[ Time Frame: During the first four weeks of treatment ]

DLTs will be assessed during the first 4 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 cycle (4 weeks) of treatment.
Secondary Outcome Measures:
1. Objective response rate (ORR)
[ Time Frame: Up to 2 years ]

The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
2. Disease control rate (DCR)
[ Time Frame: Up to 2 years ]

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.
3. Progression-free survival (PFS)
[ Time Frame: Up to 2 years ]

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.
4. Overall survival (OS)
[ Time Frame: Up to 2 years ]

Overall survival is defined as the time from the start of treatment with AK112 until death due to any cause.
5. Area under the curve (AUC) of AK112
[ Time Frame: From first dose of AK112 through 90 days after last dose of AK112 ]

The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration.
6. Maximum observed concentration (Cmax) of AK112
[ Time Frame: From first dose of AK112 through 90 days after last dose of AK112 ]

The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration.
7. Minimum observed concentration (Cmin) of AK112 at steady state
[ Time Frame: From first dose of AK112 through 90 days after last dose of AK112 ]

The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration.
8. 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 ]

The immunogenicity of AK112 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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.
Open or close this module Contacts/Locations
Central Contact Person: Xiaoping Jin, PhD
Telephone: +86 (0760) 8987 3999
Email: clinicaltrials@akesobio.com
Locations: Australia, New South Wales
Scientia Clinical Research Ltd
Randwick, New South Wales, Australia, 2031
Contact:Contact: +61 2 9382 5811
Contact:Principal Investigator: Charlotte Lemech, MBBS
Australia, Queensland
ICON Cancer Foundation
South Brisbane, Queensland, Australia, 4101
Contact:Contact: +61 3737 4500
Contact:Principal Investigator: Jermain Coward, MBBS
Australia, South Australia
Adelaide Cancer Centre
Kurralta Park, South Australia, Australia, 5037
Contact:Contact: +61 8 8292 2220
Contact:Principal Investigator: Dusan Kotasek, MBBS
Australia, Victoria
Monash Health
Clayton, Victoria, Australia, 3168
Contact:Contact: +61 3 8572 2429
Contact:Principal Investigator: Ben Markman, MBBS
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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