Efficacy of Cadonilimab in Non-squamous Non-small Cell Lung Cancer Patients Resistant to EGFR-TKI

NCT06277674 | Recruiting Phase 2

• 1 other identifier: ZF2023-252
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study was designed to evaluate the efficacy and safety of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) in combination with pemetrexed and anlotinib for treatment of elderly patients with T790M-negative advanced non-squamous non-small cell lung cancer following resistance to EGFR-TKI.

Conditions

Non-small Cell Lung Cancer

Keywords

Cadonilimab; Immune checkpoint inhibitors; EGFR-TKI resistance; elderly non-small cell lung cancer patients

Outcome Measures

Primary Outcomes (1)

• ORR(Objective response rate)

  ORR (overall response rate) is defined as sum of complete response (CR) rate and partial response (PR) rate, according to RECIST v 1.1, based on the chest, abdomen and/or brain CT/MRI evaluation. Patients will undergo a follow-up imaging examination every 6 weeks for the first year and then every 12 weeks thereafter.

  From date of randomization until the date of death or date of withdraw, whichever came first, assessed up to 120 months

Secondary Outcomes (3)

• Progression-free survival (PFS)

  From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months.

• (Disease control rate assessed by investigators) DCR (CR+PR+SD)

  From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months

• Overall survival (OS)

  From date of randomization to the date of withdraw or date of death from any cause, whichever occurs first, assessed up to 120 months.

Study Arms (1)

cadonilimab plus pemetrexed and anlotinib

EXPERIMENTAL

Twenty elderly patients (age≥65 years) with advanced non-squamous NSCLC with T790M negative after EGFR-TKI resistance will be enrollrd in this study. Participants will receive 4 to 6 cycles of cardunnilumab in combination with pemetrexed and anlotinib every 3 weeks, followed by maintenance treatment with cadonilimab plus anlotinib until disease progression, intolerable toxicity, withdrawal of consent, death, or other protocol-specified causes, whichever occurs first. Cadonilimab was administered intravenously at a dose of 10 mg/kg every 3 weeks. Pemetrexed was administered intravenously at a dose of 500 mg/m² every 3 weeks Anlotinib was taken at doses of 10mg orally once daily for two weeks on a one-week-off schedule.

Drug: Cadonilimab plus Pemetrexed and Anlotinib

Interventions

Cadonilimab plus Pemetrexed and Anlotinib DRUG

Cadonilimab was administered intravenously at a dose of 10 mg/kg every 3 weeks. Pemetrexed was administered intravenously at a dose of 500 mg/m² every 3 weeks Anlotinib was taken at doses of 10mg orally once daily for two weeks on a one-week-off schedule.

Also known as: ICIs in combination with chemotherapy and antiangiogenic therapy

cadonilimab plus pemetrexed and anlotinib

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients signed informed consent, willing to accept this regimen, able to adhere to the medication, and had good compliance.
• Patients with advanced or metastatic non-small cell lung cancer (stage IIIB, IIIC, or IV according to the AJCC staging system, 8th edition) diagnosed by histopathology or cytopathology
• Histologically or cytologically confirmed, locally advanced or metastatic nonsquamous non-small-cell lung cancer (stage IIIB, IIIC, or IV according to the AJCC staging manual, 8th edition) patients with EGFR sensitive mutations (confirmed by tumour histology, cytology, or cell-free or circulating tumour DNA) progressed after receiving EGFR tyrosine-kinase inhibitor therapy; confirmed EGFR Thr790Met negative mutation status after receiving first-generation, second-generation or third-generation EGFR tyrosine-kinase inhibitor as first-line or second-line treatment
• Eastern Cooperative Oncology Group performance status of 0 to 2
• Presence of at least one measurable lesion
• An estimated life expectancy of at least 3 months
• Good organ function was defined as hemoglobin≥90g/L (no blood transfusion within 7 days), absolute neutrophil count ≥1.5×109/L, and platelet count≥100×109/L. Total bilirubin level≤1.5 times of the upper limit of normal value (ULN), albumin ≥30g/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times of upper limit of normal (ULN), in cases with liver metastasis, AST and ALT≤5 times of ULN; Creatinine ≤1.5 times of ULN; International normalized ratio (INR) or prothrombin time (PT) ≤1.5 times of ULN, if the participant is receiving anticoagulant therapy normally, as long as the PT is within the prescribed range of anticoagulant drugs

You may not qualify if:

• Concomitant driver mutations for which there were known therapies were identified, including but not limited to ALK rearrangement, ROS1 fusion, or BRAF V600E mutation
• Previously received systemic anti-tumour therapy (including cytotoxic chemotherapy and antiangiogenic therapy) except EGFR tyrosine-kinase inhibitors for advanced NSCLC
• Previously received immunotherapy (including anti-PD-1, anti-PD-L1, or anti-CTLA-4) antibodies or agents
• The presence of an active malignancy within 2 years prior to the first dose was not allowed. Participants with locally cured tumors, such as basal-cell carcinoma or squamous-cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the breast, were not excluded
• The enrollment of another clinical study was excluded except for observational or noninterventional studies or interventional studies with a follow-up period exceeding four weeks after the last dose of the study drug or more than five half-lives of the study drug
• Patients received systemic treatment with Chinese patent medicine or Chinese herbal medicine exhibiting anti-tumor properties or immunomodulatory drugs (such as thymosin, interferon, interleukin) indicated for anti-tumor purposes within a 2-week period prior to the initial dosage
• Participants who have received systemic treatment with corticosteroids (prednisone equivalent dose \> 10 mg/day) or other immunosuppressive drugs within 14 days prior to the first dose are excluded
• Documented history of immunodeficiency
• Documented history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
• Major surgical procedures (such as laparotomy, thoracotomy, viscerectomy, etc.) or severe trauma within 28 days prior to the initial administration (intravenous drip replacement is acceptable); Surgery aimed at improving or reducing the risk of oncologic complications within 14 days before the first dose; Or incomplete recovery from any of the aforementioned previous surgeries. Major surgical procedures were planned (at the investigator's discretion) within 30 days after the initial dose. Local surgery (e.g., placement of systemic ports, core needle biopsy) was permitted if performed at least 24 hours prior to initiation of study treatment
• Patients with a medical history of gastrointestinal perforation, gastrointestinal fistula, or female genital fistula (such as vesicovaginal fistula, urethrovaginal fistula, etc.) within the past 6 months prior to the initial drug administration were eligible for enrollment if the perforation or fistula had been surgically treated (e.g., excision or repair) and if complete recovery or resolution of the condition was confirmed by the investigator
• The presence of interstitial lung disease, whether symptomatic or not, may hinder the detection or management of suspected drug-related pulmonary toxicity
• The presence of active pulmonary tuberculosis (TB). Patients suspected to have active TB underwent examination through chest X-ray and sputum analysis, while being assessed for clinical signs and symptoms

Sponsors & Collaborators

• Guangzhou University of Traditional Chinese Medicine: lead
• Akeso Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Guangdong Provincial Hospital of Traditional Chinese Medicine

Guangzhou, Guangdong, 510120, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; anlotinib; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Therapeutics

Study Officials

• Haibo Zhang, Prof

  Guangdong Provincial Hospital of Traditional Chinese Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fangfang Hou, Dr

CONTACT

86-020-81887233; 13527816095@163.com

Yadong Chen, Dr

CONTACT

86-020-81887233; 794053913@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 18, 2024
• First Posted: February 26, 2024
• Study Start: November 2, 2023
• Primary Completion: December 1, 2024
• Study Completion: June 1, 2025
• Last Updated: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)