Phase 3 Clinical Study of AK112 for NSCLC Patients

Phase 3

Active, not recruiting

• Conditions: Non-Squamous Non-small Cell Lung Cancer
• Interventions: Drug: Ivonescimab (SMT112 or AK112) Injection; Drug: Placebo Injection

• Registration Number: NCT05184712
• Lead Sponsor: Akeso

Brief Summary

A Randomized, Double-blind, Multi-center, Phase III Clinical Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Failed to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment

Detailed Description

The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare AK112 Plus Pemetrexed and Carboplatin to Placebo Plus Pemetrexed and Carboplatin in Patients with Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring. Approximately 320 subjects will be randomized to the two treatment at the ratio of 1:1. Each enrolled subject will receive an intravenous infusion of the AK112/Placebo Plus Pemetrexed and Carboplatin （Q3W,up to 4 cycles）in treatment periods per the randomization schedule. Afterward, AK112/ Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Study Timeline

• Study First Submitted: 2021-12-21
• Study First Submitted QC: 2022-01-07
• Study First Posted: 2022-01-11
• Study Start: 2022-01-25
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-24
• Primary Completion: 2024-06-28
• Last Update Posted: 2024-06-28
• Study Completion: 2025-11-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 322

Inclusion Criteria

1. Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
4. Life expectancy ≥3 months；
5. Locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-squamous NSCLC confirmed by histology or cytology, inoperable and unable to receive radiotherapy and chemotherapy;
6. The tumor histology, cytology or hematology confirmed the presence of EGFR activating mutations before enrollment
7. Have previously received EGFR-TKI treatment and the treatment has failed
8. Subjects have at least one measurable non-brain tumor lesion per RECIST v1.1
9. Major organ function prior to treatment meets the following criteria
10. Patients of childbearing potential must agree to use effective contraceptive measures

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Exclusion Criteria

1. Histological or cytological pathology confirmed the presence of small cell carcinoma components, or the main component is squamous cell carcinoma
2. There are reports confirming the existence of other driver gene mutations with known drug treatments
3. Subjects who received any prior treatments targeting the mechanism of tumor immunity
4. The subject has received systemic anti-tumor therapy other than EGFR-TKI
5. Currently enrolled in any other clinical study
6. Received EGFR-TKI treatment, palliative local treatment, non-specific immunomodulatory treatment within 2 weeks prior to the first dose; and Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 1 weeks prior to the first dose.
7. Tumor surrounds important blood vessels or has obvious necrosis, cavitation, or invades surrounding important organs and blood vessels.
8. Symptomatic central nervous system metastases
9. Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors
10. Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment
11. There is a history of major diseases 1 year prior to the first dose.
12. .Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose
13. Received chest radiation therapy prior to the first dose
14. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
15. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ivonescimab (SMT112 or AK112) in combination with Pemetrexed and Carboplatin	Ivonescimab (SMT112 or AK112) Injection	Subjects will receive Ivonescimab (SMT112 or AK112) Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.
Placebo in combination with Pemetrexed and Carboplatin	Placebo Injection	Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	Up to 2 years	Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.

Secondary Outcome Measures

Name	Time	Method
OS	Up to 2 years	Overall Survival (OS) in the ITT population
DoR	Up to 2 years	Duration of response (DoR), which 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.
ORR	Up to 2 years	Efficacy measures such as overall response rate (ORR), which is the proportion of subjects with CR or PR by IRRC based on RECIST v1.1
TTR	Up to 2 years	TTR is defined as the time to response base on RECIST v1.1
AE	From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first,up to 2 years	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.
Observed concentrations of AK112	through study completion, an average of 2 year	The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration
Number of subjects who develop detectable anti-drug antibodies (ADAs)	From first dose of AK112 through 90 days after last dose of AK112,up to 2 years	The immunogenicity of AK112 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs)
DCR	Up to 2 years	Disease control rate (DCR), which is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1
PFS	Up to 2 years	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first assessed by investigator Per RECIST 1.1.

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China