AK112 in Combination With Chemotherapy in Advanced Squamous Non-Small Cell Lung Cancer

A Randomized, Controlled, Multi-center Phase III Clinical Study of AK112 Combined With Chemotherapy Versus PD-1 Inhibitor Combined With Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Squamous Non-small Cell Lung Cancer

This trial is a Phase III study. All patients are stage IIIB/C (unsuitable for radical therapy) or stage IV squamous non-small cell lung cancer(NSCLC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of AK112 combined with chemotherapy versus Tislelizumab combined with chemotherapy in patients with advanced squamous NSCLC.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Squamous Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: AK112, Carboplatin, Paxlitaxel; Drug: Tislelizumab, Carboplatin, Paxlitaxel

• Study Type: Interventional
• Enrollment (Actual): 532
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
• ≥18 years old and ≤75 years old (at the time consent is obtained).
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has a life expectancy of at least 3 months.
• Has a histologically confirmed diagnosis of squamous NSCLC.
• Has Stage IIIB/C or IV NSCLC (American Joint Committee on Cancer [AJCC]).
• Has no prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC.
• Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Has adequate organ function.

Exclusion Criteria:

• Histological diagnosis of non-squamous NSCLC.
• Has EGFR-sensitive mutations or ALK gene translocations.
• Known ROS1 rearrangement, MET exon 14 skipping mutation, or RET gene fusion positivite.
• Is currently participating in a study of an investigational agent or using an investigational device.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment.
• Has undergone major surgery within 30 days of Study Day 1.
• 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).
• 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, congestive heart failure within 12 months prior to day 1 of study treatment.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Has received a live virus vaccine within 30 days of the planned first dose of study therapy.
• Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: AK112 in Combination With Paclitaxel Plus Carboplatin; AK112 will be administered at a selected dose intravenously (IV) every three weeks (Q3W). Carboplatin will be administered at AUC5, Q3W, intravenously (IV) for 4 cycles. Paclitaxel will be administered at 175 mg/m2, Q3W, intravenously (IV) for 4 cycles.	Drug: AK112, Carboplatin, Paxlitaxel; IV infusion,Specified dose on specified days
Active Comparator: Active Comparator: Tislelizumab in Combination With Paclitaxel Plus Carboplatin; Tislelizumab will be administered at a dose of 200 mg intravenously (IV) every three weeks (Q3W). Carboplatin will be administered at AUC5, Q3W, intravenously (IV) for 4 cycles. Paclitaxel will be administered at 175 mg/m2, Q3W, intravenously (IV) for 4 cycles.	Drug: Tislelizumab, Carboplatin, Paxlitaxel; IV infusion,Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS assessed by IRRC per RECIST v1.1	Progression-free survival (PFS) is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the blinded IRRC or death due to any cause (whichever occurs first).	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival (OS) is defined as the time from the start of treatment with AK112 until death due to any cause.	Up to approximately 2 years
ORR assessed by IRRC per RECIST v1.1	ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1.	Up to approximately 2 years
DoR assessed by IRRC per RECIST v1.1	Duration of response (DoR) assessed according to RECIST v1.1	Up to approximately 2 years
DCR assessed by IRRC per RECIST v1.1	Disease control rate (DCR) assessed according to RECIST v1.1.	Up to approximately 2 years
TTR assessed by IRRC per RECIST v1.1	Time to response (TTR) is defined as the time to response base on RECIST v1.1.	Up to approximately 2 years
PFS assessed by investigator per RECIST v1.1	Progression-free survival (PFS) is defined as the time from the date of randomization till the first documentation of disease progression assessed by the investigator or death due to any cause (whichever occurs first).	Up to approximately 2 years
ORR assessed by the investigator per RECIST v1.1	ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1.	Up to approximately 2 years
DoR assessed by the investigator per RECIST v1.1	Duration of response (DoR) assessed according to RECIST v1.1.	Up to approximately 2 years
DCR assessed by the investigator per RECIST v1.1	Disease control rate (DCR) assessed according to RECIST v1.1.	Up to approximately 2 years
TTR assessed by the investigator per RECIST v1.1	Time to response (TTR) is defined as the time to response base on RECIST v1.1.	Up to approximately 2 years
AE	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to approximately 2 years
ADA	Number of subjects with detectable anti-drug antibodies (ADA).	Up to approximately 2 years
Cmax and Cmin	AK112 serum drug concentrations in subjects at different time points after AK112 administration	Up to approximately 2 years
PD-L1 expression	The correlationship between PD-L1 expression and efficacy.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2023
• Primary Completion (Actual): February 28, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 21, 2023
• First Submitted That Met QC Criteria: April 21, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 30, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tislelizumab; Carboplatin
• Other Study ID Numbers: AK112-306

Drug and device information, study documents

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