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 (Neoadjuvant)

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 Overview

• Status: Not yet recruiting
• Conditions: Neoadjuvant Therapy; Bispecific Antibody; Resectable Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: AK104

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Zhang Peng Zhang, PhD; Phone Number: 02165115006; Email: zhangpeng1121@tongji.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK104 monotherapy PD-1 combined with chemotherapy; Enrolled patients will receive 3 cycles of AK104 monotherapy as neoadjuvant treatment, administered every 21 days.	Drug: AK104; Eligible patients will be randomly assigned in a 1:1 ratio to either the PD-1 combined with chemotherapy group or the AK104 monotherapy group. Treatment will be administered every 3 weeks, with patients undergoing three preoperative treatment cycles before surgery.; Other Names: PD-1 combined with chemotherapy

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Estimated): April 21, 2025
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 11, 2031

Study Registration Dates

• First Submitted: April 19, 2025
• First Submitted That Met QC Criteria: April 19, 2025
• First Posted (Actual): April 27, 2025

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 19, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Neoadjuvant therapy; bispecific antibody; Resectable non-small cell lung cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: LungMate-027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The researchers will consider whether IPD is available to other researchers only after the paper is published.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No