A Study of Anti-PD-1 AK105 in Patients With Metastatic Nasopharyngeal Carcinoma

NCT ID: NCT03866967

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-27
• Study Completion Date: 2024-03-22

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).

Conditions

Nasopharyngeal Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AK105

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

Group Type: EXPERIMENTAL

AK105

Intervention Type: BIOLOGICAL

intravenous (IV) infusion

Interventions

AK105

intravenous (IV) infusion

Intervention Type: BIOLOGICAL

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, 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 AK105.
• 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.
• 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 500 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <500 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, spinal cord compression, leptomeningeal disease, or active brain metastasis.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Receipt of live or attenuated vaccination within 30 days prior to the first dose of study treatment, or plan to receive live or attenuated vaccine during the study.
• Known history of server hypersensitivity to other monoclonal antibodies.
• Known severe allergic reactions to paclitaxel, carboplatin, or their preventive medications.
• Known allergic reactions to any ingredients of AK105.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Akeso Tiancheng, Inc

OTHER

Sponsor Role: collaborator

Akeso

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chaosu Hu, MD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

FuDan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Countries

China

References

Huang Z, Pang X, Zhong T, Qu T, Chen N, Ma S, He X, Xia D, Wang M, Xia M, Li B. Penpulimab, an Fc-Engineered IgG1 Anti-PD-1 Antibody, With Improved Efficacy and Low Incidence of Immune-Related Adverse Events. Front Immunol. 2022 Jun 27;13:924542. doi: 10.3389/fimmu.2022.924542. eCollection 2022.

Reference Type: DERIVED

PMID: 35833116 (View on PubMed)

Related Links

https://www.nature.com/articles/s41392-024-01865-6

Related Info

Other Identifiers

AK105-202

Identifier Type: -

Identifier Source: org_study_id