A Randomized, Double-blind, Multi-center, Phase III Study of AK112 or Placebo Combined with Pemetrexed and Carboplatin in Patients with EGFRmutant Locally Advanced or Metastatic Non-squamous NSCLC Who Have Failed to EGFR-TKI Treatment (HARMONi)
Trial Description
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
Eligibility Requirements
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
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).