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

Phase 2

Not yet recruiting

• Conditions: Resectable Non-small Cell Lung Cancer; Bispecific Antibody; Neoadjuvant Therapy
• Interventions: Drug: AK104

• Registration Number: NCT06946836
• Lead Sponsor: Shanghai Pulmonary Hospital, Shanghai, China

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.

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-19
• Study First Submitted QC: 2025-04-19
• Last Update Submitted: 2025-04-19
• Study Start: 2025-04-21
• Study First Posted: 2025-04-27
• Last Update Posted: 2025-04-27
• Primary Completion: 2031-05-01
• Study Completion: 2031-05-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AK104 monotherapy PD-1 combined with chemotherapy	AK104	Enrolled patients will receive 3 cycles of AK104 monotherapy as neoadjuvant treatment, administered every 21 days.

Primary Outcome Measures

Name	Time	Method
PCR	up to 60 months	a complete absence of viable tumor cells in the primary tumor site and surgically removed lymph nodes after neoadjuvant treatment

Secondary Outcome Measures

Name	Time	Method
MPR	up to 60 months	≤10% residual viable tumor cells in the lung and sampled lymph nodes
ORR	up to 60 months	a partial or complete response according to RECIST, version 1.1
OS	up to 60 months	the time from randomization to death from any cause
EFS	up to 60 months	the time from randomization to progression of disease, recurrence of disease, or death from any cause.
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0	up to 60 months	Incidence of serious adverse events (SAEs) occurring during treatment according to NCI-CTCAE v5.0
R0 rate	up to 60 months	Proportion of patients achieving R0 resection
Conversion rate of surgery	up to 60 months	Conversion rate from initially unresectable to resectable NSCLC following neoadjuvant therapy