NCT07412262
Not yet recruiting
Phase 2
A Prospective, Single-Arm, Multicenter, Phase II Clinical Study of Chidamide Combined With Ivonescimab in the Treatment of Advanced Non-Small Cell Lung Cancer With Acquired Resistance to Immunotherapy and High YAP Protein Expression
Guangdong Association of Clinical Trials2 sites in 1 country32 target enrollmentStarted: March 31, 2026Last updated:
InterventionsChidamide in combination with Ivonescimab
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 32
- Locations
- 2
- Primary Endpoint
- Progression Free Survival(PFS) per RECIST v1.1
Overview
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.
Detailed Description
Not provided
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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:
Exclusion Criteria
- •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;
- •Exclusion of central squamous cell lung cancer invading large blood vessels;
- •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);
Arms & Interventions
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.
Intervention: Chidamide in combination with Ivonescimab (Drug)
Outcomes
Primary Outcomes
Progression Free Survival(PFS) per RECIST v1.1
Time Frame: From the start of treatment until disease progression or death (assessed up to 24 months)
PFS is measured from the start of treatment until progression or death, whichever is first met
Secondary Outcomes
- 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(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)
Investigators
Study Sites (2)
Loading locations...
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