A Study of Chidamide Combined With Ivonescimab in the Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) With Acquired Resistance to Immunotherapy and High Yes-associated Protein (YAP) Expression

NCT07412262 | Not Yet Recruiting Phase 2

• 1 other identifier: CTONG 2505
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This is a prospective, single-arm, multi-center, phase II clinical trial to evaluate the efficacy and safety of Chidamide in combination with Ivonescimab in the treatment of advanced non-small cell lung cancer with secondary immune resistance and high YAP protein expression.

Conditions

Non-Small Cell Lung Cancer

Keywords

YAP protein; Acquired immune resistance

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival(PFS) per Response Evaluation Criteria in Solid tumors (RECIST) v1.1

  PFS is measured from the start of treatment until progression or death, whichever is first met

  From the start of treatment until disease progression or death (assessed up to 24 months)

Secondary Outcomes (5)

• Object Response Rate (ORR)

  Every 6 weeks (RECIST 1.1) until progression(up to 24 months)

• Disease Control Rate(DCR)

  From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first, up to approximately 2 years

• Duration of Response(DOR)

  From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first, up to approximately 2 years

• Overall Survival

  From the date of first dose of study drug until date of death from any cause (up to approximately 5 years).

• Adverse Events

  From first dose until 30 days after the last dose, up to approximately 2 years

Study Arms (1)

The combination of Chidamide plus Ivonescimab(AK112)

EXPERIMENTAL

Participants will take 20 mg of Chidamide by month every 3-4 days on a twice weekly (BIW) schedule and Ivonescimab (AK112) 20 mg/kg intravenously (IV) Q3W.

Drug: Chidamide in combination with Ivonescimab

Interventions

Chidamide in combination with Ivonescimab DRUG

Chidamide 20mg/dose orally BIW; Ivonescimab 20mg/kg intravenously (IV) Q3W

Also known as: Tucidinostat, CS055, AK112

The combination of Chidamide plus Ivonescimab(AK112)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be signed before implementing any trial-related procedures;
• Age ≥18 years old;
• Have histologically or cytologically confirmed locally advanced (IIIB/IIIC stage), metastatic or recurrent (IV stage) non-small cell lung cancer (NSCLC) that is not operable and not suitable for radical concurrent chemoradiotherapy, as classified by the 9th edition of the TNM staging system of the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer;
• Previously received first-line PD-1/PD-L1 inhibitor monotherapy or combination therapy, with a progression-free survival (PFS) of ≥ 6 months under the initial PD-1/PD-L1-containing treatment regimen;
• Previously received only first-line systemic treatment;
• Able to provide 15 pieces of biopsied tumor tissue or tumor tissue sections after PD-1/PD-L1 treatment resistance, pathologically confirmed as non-small cell lung cancer, and centrally laboratory-confirmed high YAP protein expression. Eligible subjects voluntarily provide 5-15 sections of tumor tissue samples from initial diagnosis. (YAP immunohistochemical staining intensity is graded as 0 (negative), 1+ (weak), 2+ (moderate), and 3+ (strong); the proportion of positive tumor cells is graded as 0 (0-5%), 1+ (6-25%), 2+ (26-50%), 3+ (51-75%), and 4+ (\>75%). The YAP IHC score is calculated by multiplying the staining intensity by the proportion of positive tumor cells: YAP IRS = Staining Intensity (A) × Proportion of Positive Tumor Cells (B). A YAP IHC score \< 6 indicates low YAP expression, and ≥ 6 indicates high YAP expression);
• Asymptomatic brain metastasis patients are eligible for enrollment;
• Palliative radiotherapy completed within 2 weeks before study enrollment is allowed, and radiotherapy-related toxicity has recovered to ≤ Grade 1 (CTCAE 5.0). Radiated lesions are not considered evaluable lesions unless there is evidence of progression after radiotherapy;
• No prior use of any traditional Chinese medicine (TCM) with anti-tumor effects, or prior use of TCM with anti-tumor effects no more than 3 times (one dose counts as one time), and discontinuation of such TCM for ≥ 2 weeks before the start of study drug treatment.
• Patients must meet the following laboratory test requirements at screening:
• Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L without the use of growth factors in the past 14 days;
• Platelet count ≥ 80 × 10⁹/L and hemoglobin ≥ 80 g/L without blood transfusion in the past 14 days;
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × Upper Limit of Normal (ULN) (patients with liver metastasis are allowed to have ALT or AST ≤ 5 × ULN);
• Total bilirubin ≤ 1.5 × ULN (patients with liver metastasis or biliary obstructive tumors are allowed to have ≤ 2.5 × ULN);
• Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate (calculated by the Cockcroft-Gault formula) ≥ 45 ml/min;

You may not qualify if:

• Have a history of severe bleeding tendency or coagulation disorders; have significant clinical bleeding symptoms within 4 weeks before enrollment, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing or expectorating ≥ 1 teaspoon of fresh blood or small blood clots or only coughing blood without sputum, subjects with blood in sputum are allowed to enroll), nasal bleeding (excluding epistaxis and retracted nasal blood); continuous antiplatelet or anticoagulant therapy within 14 days before the first dose;
• History of gastrointestinal perforation and/or fistula, gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), esophagogastric varices, severe ulcers, unhealed wounds, abdominal fistulas, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before the first dose; extensive intestinal resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea);
• Hypersensitivity to any study drug or its components;
• Patients who experienced Grade 3 or above immune-related adverse reactions with prior immunotherapy drugs, and investigators assess that immunotherapy has safety concerns with risks outweighing benefits;
• Any arterial thromboembolic event, Grade 3 or above venous thromboembolic event as specified by NCI CTCAE 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months before the first dose;
• Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before the first dose;
• Complicated with severe uncontrolled concurrent infections or other severe uncontrolled comorbidities, moderate or severe renal impairment (e.g., progressive infection, uncontrolled hypertension, diabetes mellitus, etc.);
• Active hepatitis B or C infection (hepatitis B surface antigen positive and hepatitis B virus DNA \> 1 × 10³ copies/mL; hepatitis C virus RNA \> 1 × 10³ copies/mL);
• Human Immunodeficiency Virus (HIV) infection (HIV antibody positive);
• Clinically significant active infection, active pulmonary tuberculosis;
• Past or current clinically active interstitial lung disease; current active pneumonia; current radiation pneumonitis requiring hormone therapy;
• Evidence of severe or uncontrolled systemic diseases (e.g., severe mental or neurological diseases, epilepsy, or dementia not stably controlled by drugs; unstable or decompensated respiratory, cardiovascular, hepatic, or renal diseases; uncontrolled hypertension \[i.e., hypertension ≥ CTCAE Grade 3 despite drug treatment\]; hyperglycemia \[fasting blood glucose \> 10 mmol/L\]);
• Clinically significant ventricular arrhythmia within 12 months before the first dose, atrial fibrillation not stably controlled by drugs, unstable angina pectoris, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) classification ≥ Grade 2, or vascular diseases (e.g., aortic aneurysm at risk of rupture), or other cardiac impairments that may affect the safety evaluation of study drugs (e.g., uncontrolled arrhythmia, myocardial ischemia, etc.);
• Past or current concurrent other malignant tumors (except for well-controlled non-melanoma cutaneous basal cell carcinoma, in situ breast/cervical cancer, and other malignant tumors that have been well-controlled without treatment for the past five years);
• Tumor invasion of large vascular structures (e.g., pulmonary artery, superior vena cava, or inferior vena cava) detected at screening, or obvious necrosis/cavitation, which is judged by investigators to have a high risk of bleeding;

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead
• Innovent Biologics, Inc.: collaborator
• Akesobio: collaborator

Study Sites (2)

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China

Guangzhou, Guangdong, 510080, China

Location

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, Hubei, 430030, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Qing Zhou, MD

CONTACT

+86 02083827812; gzzhouqing@126.com

Yi-chen Zhang, MD

CONTACT

86 19128287863

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 17, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: May 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)