Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative (ACHELOUS)

Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative：A Multi-center, Single-arm, Phase II Study

This is a single arm, multi-center clinical trial. Target population is advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients with Programmed Cell Death Ligand 1 (PD-L1) negative, aiming to evaluate the efficacy and safety of the combination therapy of Cadonilimab and chemotherapy. Cadonilimab is a PD-1/CTLA-4 bi-specific antibody.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Cadonilimab; Drug: Pemetrexed; Drug: Carboplatin

Detailed Description

This trial enrolled advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients with Programmed Cell Death Ligand 1 (PD-L1) negative. Patients will receive cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4 cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as maintenance therapy. The primary endpoint is 12-month progression-free-survival (PFS) rate assessed by investigators. Key secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR), time to response (TTR), progression free survival (PFS), overall survival (OS), and safety.

• Study Type: Interventional
• Enrollment (Estimated): 49
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qian Chu; Phone Number: +86 13212760751; Email: qianchu@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Qian Chu
      • Contact: Qian Chu; Phone Number: +86 13212760751; Email: qianchu@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with histologically/cytologically stage IIIB, IIIC, IV non-squamous Non-Small Cell Lung Cancer (NSCLC)
• PD-L1 TPS<1%
• Life expectancy more than 3 months
• Without EGFR-sensitive mutation (19Exon del/21Exon L858R), ALK, ROS1 gene rearrangement or fusion
• Has no prior systemic therapy; (chemotherapy and/or radiotherapy is allowed as part of neoadjuvant/adjuvant therapy. Patients who have had recurrence or metastasis for more than 6 months from the end of neoadjuvant/adjuvant treatment would be enrolled)
• ECOG score 0-1
• Patients must have at least one measurable lesion according to RECIST 1.1
• Has adequate organ function
• Agree to provide tumour tissue samples for biomarker exploration (including but not limited to PD-L1 IHC or NGS testing)
• Voluntarily sign a written informed consent form

Exclusion Criteria:

• Histological examination with Small Cell Lung Cancer or squamous Non-Small Cell Lung Cancer
• With active central nervous system (CNS) metastases confirmed by CT or MRI
• With other malignancy within 3 years before enrollment
• With severe infections within 4 weeks of the first dose of study treatment
• Women who are pregnant or lactating
• History of interstitial lung disease, drug-induced interstitial lung disease, or radiation pneumonia requiring hormone therapy
• History of myocarditis, cardiomyopathy, and malignant arrhythmia
• Tumor compresses important surrounding organs (such as the esophagus) with accompanying symptoms, compressing the superior vena cava or invading the mediastinal vessels, heart, etc.
• Risk of bleeding, major hemoptysis, or with history of coagulation dysfunction
• Active autoimmune diseases that require systematic treatment within 2 years before enrollment
• History of Human Immunodeficiency Virus (HIV)
• With active hepatitis B infection
• With uncontrollable pleural effusion, pericardial effusion, or ascites that require repeated drainage

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: Experimental Arm; Patients will receive cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4 cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as maintenance therapy.	Drug: Cadonilimab; Patients receive cadonilimab (10mg/kg) every 3 weeks.; Other Names: AK104; Drug: Pemetrexed; Patients receive pemetrexed (500mg/m2) every 3 weeks.; Drug: Carboplatin; Patients receive carboplatin (AUC=5) every 3 weeks for 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month progression-free-survival (PFS) rate	Rate of patients with complete/partial response at 12-month from enrollment	At 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence, type and severity of adverse events	Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0	From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months)
objective response rate (ORR)	objective response rate using RECIST 1.1 criteria	about 24 months
duration of response (DOR)	Time from the date of the first documented response (CR or PR) to the earliest date of disease progression (RECIST 1.1), or death due to any cause	about 24 months
disease control rate (DCR)	disease control rate using RECIST 1.1 criteria	about 24 months
time to response (TTR)	Time from the date of enrollment to the first documented response (CR or PR) (RECIST 1.1)	about 24 months
progression free survival (PFS)	Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause)	about 24 months
overall survival (OS)	Time from enrollment until death due to any cause	about 24 months

Collaborators and Investigators

• Sponsor: Qian Chu
• Collaborators: Akeso Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Qian Chu, Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: August 12, 2023
• First Submitted That Met QC Criteria: August 18, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 18, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: non-squamous Non-Small Cell Lung Cancer; Programmed Cell Death Ligand 1; cadonilimab
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Carboplatin; Pemetrexed
• Other Study ID Numbers: S019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No