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

NCT04047290 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AK112-101
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 7

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.

Conditions

Neoplasms Malignant

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  From time ICF is signed until 90 days after last dose of AK112

• 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.

  During the first four weeks of treatment with AK112

Secondary Outcomes (7)

• Objective response rate (ORR)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

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

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

Study Arms (1)

AK112

EXPERIMENTAL

AK112 IV every 2 weeks (q2w) or every 3 weeks (q3w)

Drug: AK112

Interventions

AK112 DRUG

AK112 is a PD1/VEGF bispecific antibody.

AK112

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Akesobio Australia Pty Ltd: lead

Study Sites (7)

Border Medical Oncology

Albury, New South Wales, Australia

Location

Scientia Clinical Research Ltd

Randwick, New South Wales, Australia

Location

Blacktown Hospital

Sydney, New South Wales, Australia

Location

ICON Cancer Foundation

South Brisbane, Queensland, Australia

Location

Adelaide Cancer Centre

Kurralta Park, South Australia, Australia

Location

Monash Health

Clayton, Victoria, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Location

Related Publications (1)

• 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.

  PMID: 38642937 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 6, 2019
• Study Start: September 20, 2019
• Primary Completion: February 27, 2024
• Study Completion: February 27, 2024
• Last Updated: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (7)