A Study of Penpulimab Combination Therapy in Patients With Advanced Nasopharyngeal Carcinoma

A Phase II Study of Penpulimab Combined With Chemotherapy ± Anlotinib Hydrochloride in Patients With Advanced Nasopharyngeal Carcinoma

This is a multi-center, randomized, open-label, phase II study to evaluate the efficacy and safety of anti-PD-1 antibody Penpulimab (AK105) combined with chemotherapy ± anlotinib hydrochloride in the first-line treatment of patients with advanced nasopharyngeal carcinoma.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Gemcitabine; Drug: Cisplatin; Biological: AK105; Drug: Anlotinib hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Cancer Hospital of The University of Chinese Academy of Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 stage IVb NPC (AJCC 8th).
• Metastatic NPC patients who have not recieved the first-line platinumbased chemotherapy.
• At least one measurable tumor lesion per RECIST 1.1 criteria.
• 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:

• 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.
• Is currently participating in a study of an investigational agent or using an investigational device.
• Has known active central nervous system (CNS) metastases.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment NOTE: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study.
• Has an active infection requiring systemic therapy.
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment.
• Has undergone major surgery within 30 days of Study Day 1.
• Has received a live virus vaccine within 30 days of the planned first dose of study therapy.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK105 plus Gemcitabine and Anlotinib Hydrochloride	Drug: Gemcitabine; IV infusion; Drug: Cisplatin; IV infusion; Biological: AK105; IV infusion; Drug: Anlotinib hydrochloride; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is the proportion of subjects with CR or PR based on RECIST v1.1.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is defined as the time from the date of randomization to death from any cause.	up to 2 years
Progression-free survival (PFS)	PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) or death from any cause (whichever occurs first).	up to 2 years
Disease control rate (DCR)	DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1.	up to 2 years
Duration of response (DoR)	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.	up to 2 years
Observed concentrations of AK105	The endpoints for assessment of PK of AK105 include serum concentrations of AK105 at different timepoints after AK105 administration.	From first dose of AK105 through 90 days after last dose of AK105.
Number of subjects who develop detectable anti-drug antibodies (ADAs)	The immunogenicity of AK105 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).	From first dose of AK105 through 90 days after last dose of AK105.

Collaborators and Investigators

• Sponsor: Akeso
• Collaborators: Akeso Tiancheng, Inc
• Investigators: Study Chair: Xiaozhong Chen, MD, Cancer Hospital of The University of Chinese Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Actual): June 9, 2022
• Study Completion (Actual): December 18, 2023

Study Registration Dates

• First Submitted: January 30, 2021
• First Submitted That Met QC Criteria: January 30, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; VEGF; Anti-PD-1 antibody; Nasopharyngeal Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Gemcitabine
• Other Study ID Numbers: AK105-205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No