An Open-label, Multicenter, Phase Ib/II Study of AK104, Combined Chemotherapy as First-line Therapy to Treat Locally Advanced or Metastatic Non-small Cell Lung Carcinoma

Akeso1 site in 1 country46 target enrollmentNovember 24, 2020

ConditionsLung Cancer Non-Small Cell Stage IIIB/IIIC/IV

InterventionsAK104 plus Carboplatin and Pemetrexed AK104 plus Carboplatin and paclitaxel

DrugsAK104 plus Carboplatin and Pemetrexed AK104 plus Carboplatin and paclitaxel

Overview

Phase: Phase 1
Intervention: AK104 plus Carboplatin and Pemetrexed
Conditions: Lung Cancer Non-Small Cell Stage IIIB/IIIC/IV
Sponsor: Akeso
Enrollment: 46
Locations: 1
Primary Endpoint: The number of subjects experiencing adverse events (AEs) (Phase Ib)
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase Ib/II , open-label, multicenter single arm study designed to evaluate the efficacy, safety, tolerability, pharmacokinetic (PK), and immunogenicity of AK104 combined with Carboplatin and Pemetrexed/ Paclitaxel as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer.

Registry

clinicaltrials.gov

Start Date

November 24, 2020

End Date

December 31, 2023

Last Updated

2 years ago

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 informed consent form.
•Eastern Cooperative Oncology Group (ECOG) performance score 0 or
•Expected life expectance ≥ 3 months.
•Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC.
•No prior systemic chemotherapy for advanced or metastatic NSCLC. Subjects who have received prior adjuvant chemotherapy or neoadjuvant chemotherapy with curative intent, or definitive chemoradiotherapy for advanced disease, will be eligible provided that progression has occurred \>6 months from last treatment.
•At least one measurable tumor lesion per RECIST 1.1 criteria. A lesion previously irradiated will not be considered a target lesion.
•Subjects must provide an available tumor tissue sample taken \< 1 year prior to first dose of study treatment.
•Subjects must provide wild-type epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) reported by tissue-based tests（for non-squamous NSCLC subjects only）.
•Adequate organ function.

Exclusion Criteria

•Subjects who are diagnosed as NSCLC that harbors an epidermal growth factor receptor (EGFR)-sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation.
•Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible
•Received prior treatment with EGFR inhibitors or ALK inhibitors.
•Is currently participating intervention study or has participated in a study of an investigational agent or investigational device within 4 weeks prior to administration 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 Inducible T-cell co-stimulator (ICOS) or agonists (e.g. CD40, CD137, GITR and OX40 etc).
•Subjects who received non-thoracic radiotherapy \>30 Gy within 4 weeks prior to the first dose , or thoracic radiotherapy \>30 Gy within 24 weeks prior to the first dose study drug.
•Other active 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,
•Subjects who require systemic corticosteroids (a dose equivalent to \>10 mg/day prednisone) or other immunosuppressive drugs within 14 days prior to administration of AK
•Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.

Arms & Interventions

Nonsquamous NSCLC

Intervention: AK104 plus Carboplatin and Pemetrexed

Squamous NSCLC

Intervention: AK104 plus Carboplatin and paclitaxel

Outcomes

Primary Outcomes

The number of subjects experiencing adverse events (AEs) (Phase Ib)

Time Frame: From the time of informed consent through 90 days following termination of treatment with investigational product

Objective response rate (ORR) assessed by investigator

Time Frame: Up to 2 years

Secondary Outcomes

Disease control rate (DCR)(Up to 2 years)
Duration of response (DoR)(Up to 2 years)
Progression-free survival (PFS)(Up to 2 years)
Overall survival (OS)(Up to 2 years)
Time to response (TTR)(Up to 2 years)
Minimum observed concentration (Cmin) of AK104 at steady state(From first dose of AK104 through 90 days after last dose of AK104)
Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of AK104 through 90 days after last dose of AK104)