Clinical trial NCT04172571: A Study of the Combination of Anti-PD-1 AK105 and Anlotinib in First-line Hepatocellular Carcinoma (HCC)
Official title: An Open-Label Multi-Center Phase Ib/II Study of the Combination of AK105 and Anlotinib Hydrochloride in the First-Line Treatment of Patients With Unresectable Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: VEGF
Anti-PD-1
Tyrosine Kinase Inhibitor (TKI)
Angiogenesis-related kinases
Lead sponsor: Akeso
Sponsor class: INDUSTRY
Collaborators: name: Akeso Tiancheng, Inc
First posted: 2019-11-21
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multi-center,open-label study to evaluate the efficacy and safety of anti-PD-1 antibody AK105 plus anlotinib hydrochloride in the first-line treatment of patients with unresectable hepatocellular carcinoma.


Eligibility criteria: Inclusion Criteria:

* Signed written informed consent form voluntarily.
* Male or female，age over 18 years old (inclusive) and not more than 75 years old (inclusive), when signing the ICF.
* Expected life expectance ≥ 3 months.
* Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
* Confirmation either by histology unresectable hepatocellular carcinoma..
* BCLC stage C, and non-resectable BCLC stage B .
* No prior systemic therapy for HCC.
* Child-Pugh class A and B (≤7 points).
* At least one measurable lesion according to RECIST criteria.
* Adequate hematologic and end-organ function.
* For women of childbearing potential: agreement to remain abstinent; For men: agreement to remain abstinent.

Exclusion Criteria:

* Prior treatment with anti-PD1, anti-PD-L1 or anti-CTLA-4 antibody therapy.
* Active ongoing infection requiring therapy.
* History of severe hypersensitivity reaction to another monoclonal antibody.
* Received any live attenuated vaccine within the last 30 days.
* Other malignancy requiring treatment in the prior 5 years with the exception of locally treated squamous or basal cell carcinoma.
* Pregnant, breast feeding, or planning to become pregnant.
* Active or prior documented autoimmune or inflammatory disease with some exceptions.
* Central nervous system metastases and/or carcinomatous meningitis.
* Medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication.
* Co-infection of HBV and HCV.
* Inadequately controlled arterial hypertension.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: up to approximately 18 months
Secondary outcomes:
measure: Number of subjects experiencing adverse events (AEs)
timeFrame: From the time of informed consent through 90 days after last dose of AK105
measure: Duration of response (DoR)
timeFrame: up to approximately 18 months
measure: Disease control rate (DCR)
timeFrame: up to approximately 18 months
measure: Progression-free survival (PFS)
timeFrame: up to approximately 18 months
measure: Overall survival (OS)
timeFrame: up to approximately 24 months
measure: Observed concentrations of AK105
timeFrame: From first dose of AK105 through 90 days after last dose of AK105
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose of AK105 through 90 days after last dose of AK105
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Shunchang Jiao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA General Hospital
name: Li Bai, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Han C, Ye S, Hu C, Shen L, Qin Q, Bai Y, Yang S, Bai C, Zang A, Jiao S, Bai L. Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203). Front Oncol. 2021 Jul 13;11:684867. doi: 10.3389/fonc.2021.684867. eCollection 2021.