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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04047290




Registration number
NCT04047290
Ethics application status
Date submitted
5/08/2019
Date registered
6/08/2019
Date last updated
28/10/2022

Titles & IDs
Public title
A Study of AK112, a PD-1/VEGF Bispecific Antibody, for Advanced Solid Tumors
Scientific 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 ID [1] 0 0
AK112-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms Malignant 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AK112

Experimental: AK112 - AK112 IV every 2 weeks (q2w) or every 3 weeks (q3w)


Treatment: Drugs: AK112
AK112 is a PD1/VEGF bispecific antibody.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and nature of participants with adverse events (AEs)
Timepoint [1] 0 0
From time ICF is signed until 90 days after last dose of AK112
Primary outcome [2] 0 0
Number of participants with DLTs
Timepoint [2] 0 0
During the first four weeks of treatment with AK112
Secondary outcome [1] 0 0
Objective response rate (ORR)
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
Disease control rate (DCR)
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Progression-free survival (PFS)
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Area under the curve (AUC) of AK112 for assessment of pharmacokinetics
Timepoint [5] 0 0
From first dose of AK112 through 90 days after last dose of AK112
Secondary outcome [6] 0 0
Maximum observed concentration (Cmax) and Minimum observed concentration (Cmin) of AK112
Timepoint [6] 0 0
From first dose of AK112 through 90 days after last dose of AK112
Secondary outcome [7] 0 0
Number of subjects who develop detectable anti-drug antibodies (ADAs)
Timepoint [7] 0 0
From first dose of AK112 through 90 days after last dose of AK112

Eligibility
Key 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. 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/08/2024
Actual
Sample size
Target
151
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Border Medical Oncology - Albury
Recruitment hospital [2] 0 0
Scientia Clinical Research Ltd - Randwick
Recruitment hospital [3] 0 0
Blacktown Hospital - Sydney
Recruitment hospital [4] 0 0
ICON Cancer Foundation - South Brisbane
Recruitment hospital [5] 0 0
Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [6] 0 0
Monash Health - Clayton
Recruitment hospital [7] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
- Albury
Recruitment postcode(s) [2] 0 0
- Randwick
Recruitment postcode(s) [3] 0 0
- Sydney
Recruitment postcode(s) [4] 0 0
- South Brisbane
Recruitment postcode(s) [5] 0 0
- Kurralta Park
Recruitment postcode(s) [6] 0 0
- Clayton
Recruitment postcode(s) [7] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Akesobio Australia Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04047290
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Baiyong Li
Address 0 0
Country 0 0
Phone 0 0
+86 (0760) 8987 3999
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04047290