Brief Title
A Study of a PD-1/CTLA-4 Bispecific Antibody AK104 in Patients With Metastatic Nasopharyngeal Carcinoma
Official Title
A Single-arm, Open-label, Multicenter, Phase II Study of AK104 in Patients With Metastatic Nasopharyngeal Carcinoma Who Have Progressed After At Least 2 Prior Lines of Chemotherapy
Brief Summary
This is a single-arm, open-label, multicenter, phase II study to evaluate the anti-tumor
activity, PK and immunogenicity of AK104 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).
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Objective response rate (ORR)
Secondary Outcome
Progression-free survival (PFS)
Condition
Nasopharyngeal Carcinoma
Intervention
AK-104
Study Arms / Comparison Groups
AK104
Description: AK104 IV every 2 weeks (q2w)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
140
Start Date
February 10, 2020
Completion Date
November 15, 2021
Primary Completion Date
May 15, 2021
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 1.
- 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.
- Females of childbearing potential who are sexually active with a nonsterilized male
partner must use at least one highly effective method of contraception.
- Nonsterilized males who are sexually active with a female partner of childbearing
potential must use highly effective method of contraception from Day 1 and for 120
days after the last dose of investigational product
Exclusion Criteria:
- Receipt of last radiotherapy or any anti-tumor treatment [chemotherapy, targeted
therapy] within 3 weeks prior to the first dose of study treatment, Receipt of last
Chinese herbal drugs with antitumor indications within 1 week prior to the first dose
of study treatment.
- 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 5 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 autoimmune disease that requires systematic treatment in the past
two years, 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 7days 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.
- Necrotic lesion(s) found by examinations within 4 weeks prior to enrollment, which, in
the investigator's opinion, is at risk of massive bleeding.
- Known history of interstitial lung disease.
- Known history of active tuberculosis (TB).
- Serious infections within 4 weeks prior to the first dose of study drug, including but
not limited to complications requiring hospitalization, sepsis or severe pneumonia.
- An active infection requiring systemic therapy.
- Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA
exceeding 1000 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects
with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <1000 IU/ mL)
, and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are
eligible only if the HCV RNA test results are negative.
- Major surgery (as defined by the investigator) within 30 days prior to the first dose
of study drug.
- Presence of meningeal metastasis, or active brain metastasis.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
drainage.
- 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, with the exception of alopecia.
- Receipt of live attenuated vaccination within 30 days prior to the first dose of study
treatment, or plan to receive live attenuated vaccine during the study.
- Known history of severe hypersensitivity to other monoclonal antibodies.
- Known allergic reactions to any ingredients of AK104
- Pregnant or lactating women.
- Any conditions that, in the investigator's opinion, may put subjects treated with the
study drug at risks, or interfere with the evaluation of study drug or subject safety,
or the interpretation of study results
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Ruihua Xu, MD, +86-0760-89873999, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04220307
Organization ID
AK104-204
Responsible Party
Sponsor
Study Sponsor
Akeso
Collaborators
Akeso Pharmaceuticals, Inc.
Study Sponsor
Ruihua Xu, MD, Study Chair, Sun Yat-sen University
Verification Date
January 2020