Clinical trial NCT03261011: Study of the Safety, Pharmacokinetics, and Antitumor Activity of AK104 in Subjects With 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 AK104 in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Keywords: immunotherapy
immuno-oncology
advanced solid tumors
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2017-08-24
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK104 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 AK104 as a single agent, and a dose expansion phase (Phase 1b) which will characterize treatment of AK104 as a single agent at the MTD or RP2D.


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 (to be determined). Subjects must have received no more than three prior lines of systemic therapy for advanced or metastatic disease.
* 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.

Exclusion Criteria:

* History of severe hypersensitivity reactions to other mAbs.
* 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 AK104; in the case of mAbs, 6 weeks prior to the first dose of AK104.
* Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.
* 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.
* Active or prior documented autoimmune disease within the past 2 years.
* 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 AK104 formulation.
* History of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.
* 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.
* Known history of tuberculosis.
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
* Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection except for subjects with HCC.
* An active infection requiring systemic therapy with the exception of anti-viral therapy for hepatitis as specified by the protocol.
* Receipt of live or attenuated vaccination within 30 days prior to the first dose of AK104.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: From the time of informed consent signed through 90 days after the last dose of AK104, up to 2 years and 3 months
measure: Number of participants with a Dose Limiting Toxicity (DLT)
timeFrame: During the first 4 weeks
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 3 years
measure: Disease control rate (DCR)
timeFrame: Up to 3 years
measure: Duration of response (DoR)
timeFrame: Up to 3 years
measure: Progression-free survival (PFS)
timeFrame: Up to 3 years
measure: Overall survival (OS)
timeFrame: Up to 3 years
measure: Area under the curve (AUC) of AK104
timeFrame: From first dose of AK104 through 90 days after last dose of AK104; Up to 2 years and 3 months.
measure: Maximum observed concentration (Cmax) of AK104
timeFrame: From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.
measure: Minimum observed concentration (Cmin) of AK104 at steady state
timeFrame: From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: South Brisbane
country: Australia
facility: Integrated Clinical Oncology Network (ICON)
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research/Sir Charles Gairdner Hospital
state: Western Australia
Study officials:
References: