Cadonilimab treatment for advanced small cell lung cancer

A Single-arm Multicenter Phase II Clinical Trial of Cadunilumab (Anti-PD-1/CTLA-4) in Combination With or Without Chemotherapy in Second-line Treatment for Patients With Extensive Stage Small Cell Lung Cancer

This study is testing if a new treatment called Cadonilimab, given alone or with chemotherapy, can help people with advanced small cell lung cancer who haven't responded to previous treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital of Zunyi Medical University (Academic / other)
• Drugs / interventions: cardunilizumab, chemotherapy, immunotherapy, Cadonilimab, atezolizumab, dulvalizumab, cadunilumab
• Locations: 1 site (Guizhou, ZunYi)
• Trial ID: NCT05901584 on ClinicalTrials.gov

What this trial studies

This phase II clinical study evaluates the efficacy of Cadonilimab (AK104) as a second-line treatment for patients with extensive stage small cell lung cancer (ES-SCLC) who have previously failed first-line systemic therapy. Participants will receive either Cadonilimab alone or in combination with chemotherapy, administered in 3-week cycles until treatment is no longer beneficial or intolerable. The study aims to assess progression-free survival and other outcomes, including adverse events and overall survival, while also analyzing tumor tissue samples for molecular characteristics. The goal is to determine the effectiveness of this immunotherapy approach in a challenging patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with pathologically confirmed extensive stage small cell lung cancer who have previously received platinum-based chemotherapy.

Not a fit: Patients who have not received prior systemic therapy or those with significant comorbidities affecting treatment tolerance may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with resistant small cell lung cancer.

How similar studies have performed: While there have been studies on immunotherapy for small cell lung cancer, the specific combination and approach of this trial may offer novel insights into treatment efficacy.

Eligibility criteria

Inclusion Criteria:

1. Patients voluntarily participate in this study by signing an informed consent form.
2. Pathologically confirmed diagnosis of small cell lung cancer, with imaging confirmation of extensive stage with measurable lesions.
3. Patients who have been treated with at least one line of systemic platinum-containing chemotherapy regimen (with or without immunotherapy).

4.18 - 75 years of age; ECOG PS score: 0 to 1; expected survival greater than 3 months.

5.Major organ function within 7 days prior to treatment, meeting the following criteria:

* Blood test criteria (in 14-day untransfused state):

  1. Hemoglobin (HB) ≥ 90g/L.
  2. Absolute central granulocyte value (ANC) ≥ 1.5×109/L.
  3. Platelets (PLT) ≥75×109/L.

     ②Biochemistry needs to meet the following criteria:

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  1. total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN).
  2. alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤ 2.5 × ULN, if accompanied by liver metastases, then ALT and AST ≤ 5 × ULN
  3. serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance ≥ (CCr) 60 ml/min. ③Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%).

     6.Female participants of reproductive age must use contraception methods such as IUD, pill, or condom during the study period and for 6 months after. Male participants must also agree to use contraception during the study period and for 6 months after. Additionally, female participants must have a negative serum or urine pregnancy test within 7 days prior to study entry and should not be breastfeeding.

     Exclusion Criteria:
     1. Patients with previous use of cardunilizumab.
     2. non-small cell lung cancer (including lung cancer with a mixture of small cell and non-small cell carcinoma).
     3. Patients with other types of cancer that occurred within the past 5 years or are currently present, with the exception of treated cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors that have not invaded the basement membrane (Ta, Tis, and T1).
     4. Systemic antitumor therapy, including cytotoxic therapy, signal transduction inhibitors, immunotherapy, within 4 weeks prior to enrollment or planned during the current study dosing period (or have used mitomycin C within 6 weeks prior to treatment with the trial drug). Have had extended field radiotherapy (EF-RT) within 4 weeks prior to subgroup or have had field-limited radiotherapy to the tumor lesion to be evaluated within 2 weeks prior to subgroup.
     5. Unremitted toxic reactions due to any prior treatment above CTCAE grade 1, excluding alopecia and neurotoxicity ≤ grade 2 due to oxaliplatin.
     6. Individuals with various factors such as difficulty swallowing, chronic diarrhea, and intestinal obstruction may experience challenges with oral drug administration.
     7. with pleural effusion or ascites causing respiratory syndrome (≥ CTCAE grade 2 dyspnea).
     8. Patients with brain metastases with symptoms or symptoms controlled for less than 2 months.
     9. Patients with any severe and/or uncontrolled disease, including:

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  1. Patients with poorly controlled blood pressure (systolic blood pressure ≥ 150 mmHg and diastolic blood pressure ≥ 100 mmHg).
  2. Patients with myocardial ischemia of grade I or higher, myocardial infarction, arrhythmias (including QTc ≥ 480 ms), and congestive heart failure of grade 2 or higher (categorized according to the New York Heart Association (NYHA) classification) are included.
  3. Active or uncontrolled serious infection (≥ CTC AE grade 2 infection).
  4. Cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis requiring antiviral therapy.
  5. Renal failure requiring hemodialysis or peritoneal dialysis.
  6. This refers to a medical history of immunodeficiency, which can be acquired through HIV or other diseases, or congenital in nature. It also includes a history of organ transplantation.
  7. poorly controlled diabetes (fasting blood glucose (FBG) \>10 mmol/L).
  8. urine routine suggesting urine protein ≥++ and confirmed 24-hour urine protein quantification \>1.0 g.
  9. Patients with seizures and requiring treatment. 10. Participants who have undergone major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to the start of the study will be excluded.

     11.Patients whose imaging shows that the tumor has invaded the critical vascular perimeter or who, in the judgment of the investigator, are at high risk of fatal hemorrhage due to tumor invasion of a critical vessel during the follow-up study.

     12.Patients with any physical signs or history of bleeding, regardless of severity; patients with any bleeding or hemorrhagic event ≥ CTCAE grade 3, unhealed wounds, ulcers or fractures within 4 weeks prior to subgroup.

     13.Individuals who have experienced an arterial or venous thrombotic event within the past 6 months, including cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis, and pulmonary embolisms, should take caution.

     14.Individuals with a history of psychotropic substance abuse or psychiatric disorders who are unable to abstain.

     15.having participated in clinical trials of other antineoplastic drugs within four weeks.

     16.Patients with concomitant diseases that are deemed to pose a significant risk to their safety or may hinder their ability to complete the study, as determined by the investigator, will be excluded.

Where this trial is running

Guizhou, ZunYi

• The Second Affiliated Hospital of Zunyi Medical University — Guizhou, ZunYi, China (Recruiting)

Study contacts

• Principal investigator: Hu Ma, Ph.D — The Second Affiliated Hospital of Zunyi Medical University
• Study coordinator: Hu Ma, Ph.D

Conditions Immunotherapy; Second-line Treatment; Cardunilizumab; Small cell lung cancer