Clinical trial NCT06946836: Comparison of Neoadjuvant Cadonilimab Versus Chemotherapy Combined With PD-1 in the Treatment of Resectable Non-Small Cell Lung Cancer With High PD-L1 Expression: A Single-Center, Randomized, Exploratory Clinical Study
Official title: Comparison of Neoadjuvant Cadonilimab Versus Chemotherapy Combined With PD-1 in the Treatment of Resectable Non-Small Cell Lung Cancer With High PD-L1 Expression: A Single-Center, Randomized, Exploratory Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Resectable Non-small Cell Lung Cancer
Bispecific Antibody
Neoadjuvant Therapy
Keywords: Resectable non-small cell lung cancer
bispecific antibody
Neoadjuvant therapy
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
First posted: 2025-04-27
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Eligible patients will be randomly assigned in a 1:1 ratio to either the immunotherapy-combined chemotherapy group or the AK104 monotherapy group. Treatment will be administered every 3 weeks, with patients undergoing three preoperative treatment cycles before surgery.
Primary purpose: TREATMENT

Brief summary: The advent of immunotherapy has changed the treatment landscape for patients with non-small cell lung cancer. It has become the mainstay of perioperative treatment for patients with resectable non-small cell lung cancer。 Cadonilimab is the world's first bispecific antibody drug targeting PD-1 and CTLA-4. Previous studies on AK104 have demonstrated preliminary efficacy in both treatment-naïve advanced NSCLC patients and immunotherapy-resistant patients, showing a favorable safety and tolerability profile. This study aims to evaluate the effectiveness of neoadjuvant bispecific antibody AK104 compared with neoadjuvant chemotherapy combined with a PD-1 inhibitor in the treatment of resectable non-small cell lung cancer (NSCLC) with high PD-L1 expression.

Detailed description: The advent of immunotherapy has changed the treatment landscape for patients with non-small cell lung cancer. It has become the mainstay of perioperative treatment for patients with resectable non-small cell lung cancer。 Cadonilimab is the world's first bispecific antibody drug targeting PD-1 and CTLA-4. Previous studies on AK104 have demonstrated preliminary efficacy in both treatment-naïve advanced NSCLC patients and immunotherapy-resistant patients, showing a favorable safety and tolerability profile. This study aims to evaluate the effectiveness of neoadjuvant bispecific antibody AK104 compared with neoadjuvant chemotherapy combined with a PD-1 inhibitor in the treatment of resectable non-small cell lung cancer (NSCLC) with high PD-L1 expression.

Eligibility criteria: Inclusion Criteria:

* The patient shall sign the Informed Consent Form.

  1. Aged 18 ≥ years.
  2. Histological or cytological diagnosis of NSCLC by needle biopsy, and stage IB-IIIA confirmed by imageological examinations (CT, PET-CT or EBUS) and Treatment-naïve for relevant antitumor therapy .
  3. Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1.
  4. Life expectancy is at least 12 weeks.
  5. At least 1 measurable lesion according to RECIST 1.1.
  6. Patients with good function of other main organs (liver, kidney, blood system, etc.)
  7. Patients with lung function can tolerate surgery;
  8. Without systematic metastasis (including M1a, M1b and M1c);
  9. Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of serplulimab (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative.
  10. Unsterilized male patients must voluntarily use effective contraception during the study period not less than 120 days after chemotherapy or the last dose of serplulimab (whichever is later).

Exclusion Criteria:

* 1.Histology suggestive of small cell component and Participants who have received any systemic anti-cancer treatment for thymic epithelial tumor, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment and experimental treatment; 2. Participants with any unstable systemic disease (including active infection, uncontrolled hypertension), unstable angina pectoris, angina pectoris starting in the last three months, congestive heart failure (\>= NYHA) Grade II), myocardial infarction (6 months before admission), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases; 3. With activate or suspectable autoimmune disease, or autoimmune paracancer syndrome requiring systemic treatment; 4. Participants who are allergic to the test drug or any auxiliary materials; 5. Participants with Interstitial lung disease currently; 6. Participants with active hepatitis B, hepatitis C or HIV; 7. Pregnant or lactating women; 8. Participants suffering from nervous system diseases or mental dieases that cannot cooperate; 9.Participated in another therapeutic clinical study; Other factors that researchers think it is not suitable for enrollment.

Primary outcomes:
measure: PCR
timeFrame: up to 60 months
Secondary outcomes:
measure: MPR
timeFrame: up to 60 months
measure: ORR
timeFrame: up to 60 months
measure: OS
timeFrame: up to 60 months
measure: EFS
timeFrame: up to 60 months
measure: Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0
timeFrame: up to 60 months
measure: R0 rate
timeFrame: up to 60 months
measure: Conversion rate of surgery
timeFrame: up to 60 months
Other outcomes:
Locations:
Study officials:
References: