Safety and Efficacy of Adebrelimab Plus Irinotecan Liposome (II) With or Without Famitinib in ES-SCLC Pre-treated With Immunotherapy

A Randomized, Multi-cohort, Multi-center Phase Ib/II Study of Adebrelimab Plus Irinotecan Liposome (II) With or Without Famitinib in Patients With ES-SCLC Pre-treated With Immune Checkpoint Inhibitor(s)

This is an open-label, randomized, multi-cohort, multi-center, phase Ib/II study to evaluate the safety and efficacy of Adebrelimab plus Irinotecan Liposome (II) with or without Famitinib in patients with extensive-stage small cell lung cancer (ES-SCLC) pre-treated with immune checkpoint inhibitor(s).

Study Overview

• Status: Not yet recruiting
• Conditions: Extensive-stage Small-cell Lung Cancer
• Intervention / Treatment: Drug: Adebrelimab, Irinotecan Liposome (II); Drug: Adebrelimab, Irinotecan Liposome (II), Famitinib

Detailed Description

This study is divided into two stages. Dose exploration will be conducted first, and after obtaining preliminary safety data it will be decided by investigator when to proceed with dose extension. The aim of this study is to observe and evaluate the safety and efficacy of Adebrelimab plus Irinotecan Liposome (II) with or without Famitinib.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Baohui Han, M.D; Phone Number: 18930858216; Email: 18930858216@163.com

Study Locations

• China
  • Shanghai, China
    • Shanghai Chest Hospital
    • Contact: Baohui Han, M.D; Email: 18930858216@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Willing to participate and sign the informed consent form.
• Age: 18-75 years old, male or female.
• ECOG PS: 0-1 points.
• Histologically or cytologically confirmed of extensive stage small cell lung cancer (according to the International Association for the Study of Lung Cancer, 8th Edition or VALG II staging system).
• Progression after first-line immunotherapy combined with platinum-based system therapy more than 90 days.
• At least one measurable lesion (RECIST 1.1 criteria) was assessed by imaging evaluation (enhanced CT or MRI) within 4 weeks prior to enrollment.
• Patients with asymptomatic or treatment-stabilized central nervous system (CNS) metastases must meet the following conditions: (1) No imaging progress for at least 4 weeks after the end of treatment; (2) completion of treatment 4 weeks before enrollment; (3) no treatment with systemic corticosteroids (>10mg/ day prednisone or other equivalent dose) within the first 2 weeks before enrollment.
• Expected survival time ≥12 weeks.

• Adequate hematology and organ function (No blood transfusion or blood products, no correction with G-CSF and other hematopoietic stimulating factors within 14 days), including:

  1. Complete blood count: White blood cell count WBC≥3.0×109/L; Absolute neutrophil count ANC≥1.5×109/ L; Platelet count≥100×109/ L; Hemoglobin≥90 g/L.
  2. Liver function: AST≤2.5× upper limit of normal(ULN); ALT≤2.5×ULN (Patients with liver metastasis, AST and ALT≤5×ULN); TBIL≤1.5×ULN (Except for Gilbert syndrome ≤3×ULN); ALB≥30.0 g/L.
  3. Renal function: Serum creatinine≤1.5×ULN or creatinine clearance≥50ml/min (Cockcroft-Gault formula).
  4. Normal coagulation function: INR and APTT≤1.5×ULN.
  5. TSH≤ULN.
  6. Other: Lipase≤1.5×ULN (Patients with lipase>1.5×ULN but no clinical or imaging evidence of pancreatitis could be enrolled); Amylase≤1.5×ULN (Patients with amylase >1.5×ULN but no clinical or imaging evidence of pancreatitis could be enrolled); ALP≤2.5×ULN (Patients with bone metastasis, ALP≤5×ULN).
  7. Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF)≥50%.
• Women of childbearing potential must undergo a negative pregnancy test (HCG) 7 days prior to initiation of treatment, and women of childbearing potential and men (who are sexually active with women of childbearing potential) must agree to use effective contraception uninterruptedly for the duration of the treatment period and for 3 months after the administration of the last therapeutic dose.

Exclusion Criteria:

• Non-small cell lung cancer or non-small cell lung cancer admixed with components of small cell lung cancer, as confirmed by histology or cytology.
• With > 2 lines of prior chemotherapy.
• Patients previously treated with topoisomerase I inhibitors.
• With primary resistance, defined as patients who do not respond to first-line treatment or progress within 90 days after the end of treatment.
• Patients previously treated with antiangiogenic drugs, such as bevacizumab, recombinant human endostatin, anlotinib, apatinib, etc.
• Radiotherapy for the chest and whole brain was completed within 4 weeks prior to enrollment (enrollment was allowed if palliative radiotherapy for bone lesions could complete before the first dose).
• Except for alopecia and fatigue, toxicity due to previous antitumor therapy did not recover to CTCAE 5.0≤1 level before enrollment. Other toxicities due to previous antitumor therapy are not expected to resolve and have long-lasting sequelae.
• With active brain metastasis or meningeal metastasis. Compressive myelopathy that has not been cured or alleviated after surgery and/or radiotherapy, or present with compressive paraplegia or paraplegia after treatment in patients previously diagnosed with compressive myelopathy. Patients with liver metastases had significant clinical symptoms and abnormal liver function after cryotherapy and radiofrequency ablation treatment within the first 4 weeks of enrollment. Patients with uncontrolled mass pleural effusion, pericardial effusion, or ascites. Patients with cardiovascular disease.
• Patients previously treated with systemic immunosuppressive medications within 4 weeks before enrollment.
• Presence or history of active autoimmune disease. Interstitial pneumonia, drug-induced pneumonia, radiation pneumonia requiring steroid treatment (greater than 10 mg/day prednisone or its equivalent), or active pneumonia with clinical symptoms.
• Patients with an active or uncontrolled severe infection (CTCAE 5.0≥2) within 2 weeks prior to the first dose.
• With active tuberculosis or tuberculosis under treatment.
• Congenital or acquired immunodeficiency, such as human immunodeficiency virus (HIV) infection. Untreated active hepatitis B (HBsAg positive or HBV DNA≥500 IU/ml with abnormal liver function), hepatitis C (hepatitis C antibody positive, with higher HCV-RNA than the lower detection limit of the assay method and abnormal liver function) or hepatitis B and C co-infection.
• Hypertension that cannot be controlled with medications (systolic blood pressure≥140 mmHg or diastolic blood pressure≥90 mmHg). History of hypertensive crisis or hypertensive encephalopathy.
• Arteriovenous thrombosis events occurred within 24 weeks prior to signing the ICF, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
• With factors influencing absorption of drug, such as refractory nausea and vomiting, chronic gastrointestinal diseases, or inability to swallow the formulated product.
• With mental illness, alcoholism, inability to quit smoking, drug or substance abuse.
• With known allergic history of the drug components of this program, or allergic to other monoclonal antibodies.
• Received any other investigational treatment or participated in any other interventional clinical trials within 4 weeks prior to signing the ICF.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adebrelimab plus Irinotecan Liposome (II); Adebrelimab: 1200 mg, IV, D1, Q3W Irinotecan Liposome (II): RP2D, IV, D1, Q3W	Drug: Adebrelimab, Irinotecan Liposome (II); Adebrelimab:1200 mg, IV, D1, Q3W Irinotecan Liposome (II): RP2D, IV, D1, Q3W Escalating doses to determine recommended phase 2 dose (RP2D) of Irinotecan Liposome (II). Participants will receive Adebrelimab (1200 mg, IV, D1, Q3W) plus the RP2D of Irinotecan Liposome (II).
Experimental: Adebrelimab plus Irinotecan Liposome (II) and Famitinib; Adebrelimab: 1200 mg, IV, D1, Q3W Irinotecan Liposome (II): RP2D, IV, D1, Q3W Famitinib: RP2D, QO, QD	Drug: Adebrelimab, Irinotecan Liposome (II), Famitinib; Adebrelimab:1200 mg, IV, D1, Q3W Irinotecan Liposome (II): RP2D, IV, D1, Q3W Famitinib: RP2D, QO, QD Escalating doses to determine recommended phase 2 dose (RP2D) of Famitinib. Participants will receive Adebrelimab (1200 mg, IV, D1, Q3W) plus the RP2D of Irinotecan Liposome (II) and Famitinib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month progression-free survival	Proportion of disease progression or death from randomization to 6 months of treatment.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0.	Up to 3 months after the last dose
Objective response rate	Objective response rate, determined according to RECIST v1.1 criteria.	Up to 36 months
Progression-free survival	Progression Free Survival, determined according to RECIST v1.1 criteria.	Up to 36 months
Overall survival	Overall survival is the time from randomization to death due to any reason or loss of follow-up.	Up to 36 months
Disease control rate	Disease Control Rate, determined according to RECIST v1.1 criteria.	Up to 36 months
Duration of response	Duration of Response, determined according to RECIST v1.1 criteria.	Up to 36 months

Collaborators and Investigators

• Sponsor: Baohui Han

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: MA-SCLC-II-015

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