Phase 3 Clinical Study of AK112 for NSCLC Patients

Overview

A Randomized, Double-blind, Multi-center, Phase III Clinical Study of Ivonescimab (SMT112 or AK112) or Placebo Plus Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Progressed on or Following Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment (HARMONi)

Description

The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare Ivonescimab (SMT112 or 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 470 subjects will be randomized to two treatment arms at the ratio of 1:1. Each enrolled subject will receive an intravenous infusion of Ivonescimab (SMT112 or AK112) Plus Pemetrexed and Carboplatin or Placebo Plus Pemetrexed and Carboplatin（Q3W, up to 4 cycles) in treatment periods per the randomization schedule. Afterward, Ivonescimab (SMT112 or AK112) Plus Pemetrexed or Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Eligibility

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 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 3rd generation EGFR-TKI treatment and have progressed on or following
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

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.
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).