Using Cadonilimab to treat elderly patients with resistant non-small cell lung cancer

A Phase II Clinical Trial Evaluating the Efficacy of Cadonilimab 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.

This study is testing if a new combination treatment can help older patients with tough-to-treat lung cancer feel better and manage their disease.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 65 Years and up
• Sex: All
• Sponsor: Guangzhou University of Traditional Chinese Medicine (other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, cadonilimab, anlotinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06277674 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of cadonilimab, an anti-PD-1 and CTLA-4 bispecific antibody, in combination with pemetrexed and anlotinib for elderly patients (aged 65 and older) with advanced non-squamous non-small cell lung cancer (NSCLC) who have developed resistance to EGFR-TKI therapy. The study aims to enroll 20 participants and administer 4 to 6 cycles of the treatment, followed by maintenance therapy until disease progression or other specified reasons for discontinuation. Regular imaging assessments will be conducted to monitor treatment response and safety throughout the study duration.

Who should consider this trial

Good fit: Ideal candidates are elderly patients aged 65 and older with advanced non-squamous NSCLC who are T790M-negative and have progressed after EGFR-TKI therapy.

Not a fit: Patients with squamous cell lung cancer or those who are not elderly may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for elderly patients with advanced non-squamous NSCLC who have limited treatment choices due to EGFR-TKI resistance.

How similar studies have performed: Other studies have shown promise with immune checkpoint inhibitors in similar patient populations, but this specific combination approach is novel.

Eligibility criteria

Inclusion Criteria:

1. Patients signed informed consent, willing to accept this regimen, able to adhere to the medication, and had good compliance.
2. 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
3. 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
4. Eastern Cooperative Oncology Group performance status of 0 to 2
5. Presence of at least one measurable lesion
6. An estimated life expectancy of at least 3 months
7. 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

Exclusion Criteria:

1. Concomitant driver mutations for which there were known therapies were identified, including but not limited to ALK rearrangement, ROS1 fusion, or BRAF V600E mutation
2. Previously received systemic anti-tumour therapy (including cytotoxic chemotherapy and antiangiogenic therapy) except EGFR tyrosine-kinase inhibitors for advanced NSCLC
3. Previously received immunotherapy (including anti-PD-1, anti-PD-L1, or anti-CTLA-4) antibodies or agents
4. 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
5. 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
6. 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
7. Participants with an active, known, or suspected autoimmune disease or a history of autoimmune disease are excluded from the study, except for those with Vitiligo, alopecia, Graves' disease, psoriasis, or eczema that do not require systemic treatment for nearly 2 years. Additionally, Participants with asymptomatic hypothyroidism (due to autoimmune thyroiditis) or stable doses of hormone replacement therapy and type I diabetes requiring only stable doses of insulin replacement therapy are also exempted. Furthermore, participants who had childhood asthma that has completely resolved and no longer require any intervention in adulthood or whose disease does not recur without an external trigger are eligible for inclusion
8. 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
9. Documented history of immunodeficiency
10. Documented history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
11. 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
12. 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
13. The presence of interstitial lung disease, whether symptomatic or not, may hinder the detection or management of suspected drug-related pulmonary toxicity
14. 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

Where this trial is running

Guangzhou, Guangdong

• Guangdong Provincial Hospital of Traditional Chinese Medicine — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Haibo Zhang, Prof — Guangdong Provincial Hospital of Traditional Chinese Medicine
• Study coordinator: Fangfang Hou, Dr

Conditions: Non-small Cell Lung Cancer, Cadonilimab, Immune checkpoint inhibitors, EGFR-TKI resistance, elderly non-small cell lung cancer patients