Neoadjuvant/Adjuvant Cadonilimab Plus Chemotherapy in Patients With Resectable PD-L1 Negative NSCLC

Neoadjuvant or Adjuvant Cadonilimab (PD-1/CTLA-4 Bispecific Antibody) Plus Chemotherapy in Patients With Resectable Stage IB (≥4 cm) to IIIB(N2) PD-L1 Negative Non-small Cell Lung Cancer

The purpose of this study is to observe and evaluate the efficacy and safety of cadonilimab combined with chemotherapy in patients with resectable IB (≥ 4cm) - IIIB (N2) stage PD-L1 negative non-small cell lung cancer

Study Overview

• Status: Recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: cadonilimab+paclitaxel/albumin-bound paclitaxel+carboplatin

Detailed Description

This study is design to prospectively investigate the safety and efficacy of cadonilimab combined with chemotherapy in patients with resectable IB (≥ 4cm) - IIIB (N2) stage PD-L1 negative NSCLC. This is a single-institution, single-arm phase 2 clinical trial. Patients will receive 3 cycles of neoadjuvant chemotherapy. The surgery was performed 3-6 weeks after the completion of neoadjuvant chemotherapy. After surgery patients could receive up to 12 months of adjuvant chemotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Li Juan, Ph.D; Phone Number: 138 8027 6636; Email: dr.lijuan@hotmail.com

Study Locations

• China
  • Sichuan
    • Chendu, Sichuan, China, 610000
      • Recruiting
      • Sichuan Provincial Tumor Hospital
      • Contact: Li Juan, MD.; Phone Number: 138 8027 6636; Email: dr.lijuan@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years and ≤ 70 years
• Patients with non-small cell lung cancer diagnosed by pathologic histology or cytology, and the primary focus or lymph node metastasis test is clearly negative for EGFR/ALK/ROS1;
• Tumor tissue PD-L1 expression TPS <1%
• Patients with resectable stage IB (≥4 cm) to IIIB (N2) NSCLC (according to the staging criteria of the American Joint Committee on Cancer, 7th edition)
• Eastern Cooperative Oncology Group performance-status score of 0 or 1
• No previous anticancer therapy
• Patients had to have measurable disease according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and pretreatment tumor tissue available to assess the expression of programmed death ligand 1 (PD-L1)
• Normal function of major organs

Exclusion Criteria:

• Patients with large cell carcinoma and mixed cell lung cancer, mixed with small cell lung cancer components;
• Presence of locally advanced unresectable or metastatic disease;
• Patients in whom imaging shows that the tumor has invaded a vital vascular perimeter or in whom, in the judgment of the investigator, there is a high likelihood that the tumor will invade a vital vessel and cause a fatal hemorrhage during the follow-up study; or patients in whom there is a significant cavitating or necrotic tumor in the lung;
• Has undergone any systemic anticancer therapy for NSCLC, including cytotoxic drug therapy, immunologic drug therapy, experimental therapy;
• Has undergone localized radiotherapy for NSCLC;
• Patients who have had a cancer other than NSCLC in the five years prior to the start of treatment in this study. Patients with cancers other than NSCLC within five years prior to the start of treatment in this study. Excluding cervical carcinoma in situ, cured basal cell carcinoma, and epithelial tumors of the bladder [including Ta and Tis];
• Allergy to cardunculizumab or any component of the chemotherapeutic agent;
• Patients with the presence of any severe and/or uncontrolled disease
• Previous interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis requiring hormonal therapy, or any active interstitial lung disease with clinical evidence;
• Patients who have had a cerebrovascular accident (including temporary ischemic attack) and pulmonary embolism within 6 months;
• Current peripheral neuropathy of ≥ CTCAE grade 2, except as a result of trauma; patients requiring total right lung resection; subjects who have had major surgery or severe trauma and whose effects of surgery or trauma have resolved less than 14 days prior to enrollment
• Patients who are participating in another clinical study or who are less than 4 weeks from the end of treatment in the previous clinical study;
• History of known severe hypersensitivity reactions to other monoclonal antibodies;
• Pregnant or lactating women;
• Previous history of definite neurologic or psychiatric disorders, including epilepsy or dementia;
• Patients who, in the judgment of the investigator, may have other factors that could lead to termination of the study, such as other serious medical conditions or serious laboratory abnormalities or other family or social factors that could affect the safety of the subject or the collection of trial data and samples.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: Cadonilimab +Paclitaxel/ Albumin-bound paclitaxel +Carboplatin; Drug:Cadonilimab +Paclitaxel/ Albumin-bound paclitaxel+Carboplatin neoadjuvant chemotherapy[Cadonilimab, 10mg/kg ,d1,q3w; Paclitaxel 175mg/m2 ivgtt d1/Albumin-bound paclitaxel 260mg/m2,ivgtt(>30min) ,d1,q3w; carboplatin AUC 5 ivgtt d1, q3w] for 3 cycles.The patient was evaluated after 3 cycles of neoadjuvant chemotherapy. The surgery was performed 3-6 weeks after the completion of neoadjuvant chemotherapy. After surgery patients could receive up to 12 months of adjuvant chemotherapy.

Drug: cadonilimab+paclitaxel/albumin-bound paclitaxel+carboplatin; PD-1/CTLA-4 bispecific antibody，Cadonilimab 10mg/kg IV, q3w, paclitaxel 175mg/m2 or albumin-bound paclitaxel 260mg/m2 ivgtt d1, q3w carboplatin AUC 5 ivgtt d1, q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response (MPR)	MPR is defined as the percentage of residual viable tumour cells (%RVT) in the tumour bed of no more than 10%.	At time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response (pCR)	pCR is defined as no invasive and no in situ residuals in lung and nodes	At time of surgery
Objective response rate (ORR)	ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1	Up to 1 year
Event free survival at 24 months (EFS24)	EFS24 is defined as patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 24 months from diagnosis.	Up to 2 year
Treatment-Emergent Adverse Event (TEAE)	TEAE is defined as any adverse and unexpected change in body structure, function, or chemistry or any exacerbation of an existing condition (i.e., any clinically significant adverse change in frequency and/or intensity) during treatment. The type, frequency, and severity of TEAE will be assessed during treatment.	Up to 2 year

Collaborators and Investigators

• Sponsor: Sichuan Cancer Hospital and Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Carboplatin; Paclitaxel
• Other Study ID Numbers: EK2024001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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