A Single-arm, Open-label, Multicenter Phase II Clinical Study of AK105 in Patients With Metastatic Nasopharyngeal Carcinoma After Failure of Second and Subsequent Lines of Chemotherapy

Akeso2 sites in 1 country130 target enrollmentMarch 27, 2019

ConditionsNasopharyngeal Carcinoma

InterventionsAK105

DrugsAK105

Overview

Phase: Phase 2
Intervention: AK105
Conditions: Nasopharyngeal Carcinoma
Sponsor: Akeso
Enrollment: 130
Locations: 2
Primary Endpoint: Objective response rate (ORR) assessed by IRRC per RECIST v1.1 for anti-tumor activity in the Full Analysis Set (FAS) population
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multicenter, single-arm open-label, phase II study to evaluate the anti-tumor activity, safety, PK and immunogenicity of AK105 (Anti-PD1 antibody) in patients with metastatic nasopharyngeal carcinoma who have progressed after at least 2 prior lines of systemic chemotherapy (of which one of them must be platinum-based chemotherapy).

Registry

clinicaltrials.gov

Start Date

March 27, 2019

End Date

March 22, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Akeso

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed written informed consent form voluntarily.
•Age over 18 years old (inclusive) and not more than 75 years old (inclusive), when signing the ICF.
•Eastern Cooperative Oncology Group (ECOG) performance score 0 or
•Expected life expectance ≥ 3 months.
•Histologically confirmed diagnosis of nonkeratinizing differentiated or undifferentiated NPC.
•Not suitable for radical local therapy.
•Stage IVb metastatic NPC patients who have failed the first-line platinum-based chemotherapy and the second-line chemotherapy.
•At least one measurable tumor lesion per RECIST 1.1 criteria. A lesion previously treated with local therapies such as radiotherapy can be considered a target lesion if there is objective evidence of progression in the lesion.
•Subjects must provide an available tumor tissue sample taken within 3 years prior to enrollment.
•Adequate organ function.

Exclusion Criteria

•Receipt of last radiotherapy or any anti-tumor treatment \[chemotherapy, targeted therapy, immunotherapy, Chinese herbal drugs with antitumor indications, or immunomodulators or tumor embolization\] within 4 weeks prior to the first dose of study treatment. Nitrosourea or mitomycin C treatment within 6 weeks prior to the first dose of AK
•Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody, or any other antibody or drug therapy for T cell co-stimulatory or checkpoint pathways, such as ICOS or agonists (e.g. CD40, CD137, GITR and OX40 etc).
•Other invasive malignancies within 2 years, except for locally treatable (manifested as cured) malignancies, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ.
•Subjects with active, known or suspected autoimmune disease, or a medical history of autoimmune disease, with the exceptions of the following: vitiligo, alopecia, Grave disease, psoriasis or eczema not requiring systemic treatment within the last 2 years, hypothyroidism (caused by autoimmune thyroiditis) only requiring steady doses of hormone replacement therapy and type I diabetes only requiring steady doses of insulin replacement therapy, or completely relieved childhood asthma that requires no intervention in adulthood, or primary diseases that will not relapse unless triggered by external factors.
•Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
•Subjects who require systemic corticosteroids (a dose equivalent to \>10 mg/day prednisone) or other immunosuppressive drugs within 14 days prior to the first dose of study drug.
•Known history of testing positive for human immunodeficiency virus (HIV).
•Known history of primary immunodeficiency virus infection.
•Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
•History of gastrointestinal perforation and/ or fistula within 6 months prior to enrollment.

Arms & Interventions

AK105

Subjects receive AK105 200 mg intravenously (IV) once every 2 weeks (Q2W) until progression.

Intervention: AK105

Outcomes

Primary Outcomes

Objective response rate (ORR) assessed by IRRC per RECIST v1.1 for anti-tumor activity in the Full Analysis Set (FAS) population

Time Frame: up to 2 years

ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.

Secondary Outcomes

Overall survival (OS)(up to 2 years)
Duration of response (DoR) as assessed by IRRC and investigator(up to 2 years)
Observed concentrations of AK105(From first dose of AK105 through 90 days after last dose of AK105)
ORR as assessed by investigator per RECIST v1.1 for anti-tumor activity in the FAS population(up to 2 years)
Progression-free survival (PFS) as assessed by IRRC and investigator(up to 2 years)
Disease control rate (DCR) as assessed by IRRC and investigator(up to 2 years)
Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of AK105 through 90 days after last dose of AK105)
Time to response (TTR) assessed by IRRC and investigator ；(up to 2 years)
Incidence and severity of treatment-emergent adverse events (TEAEs)(From the time of informed consent signed through 90 days after last dose of AK105)