A Study to Investigate the Efficacy and Safety of Ivonescimab Combined With Irinotecan Liposome as Second-line Regimen for ES-SCLC

Phase II Study of AK112 Combined With Irinotecan Liposome in Patients With ES-SCLC Who Progressed on Immune Checkpoint Inhibitors and Chemotherapy.

This is an open-label, single-arm, prospective phase 2 study, evaluating the efficacy and safety of ivonescimab combined with irinotecan liposome for relapsed extensive stage small cell lung cancer, who progressed on PD-(L)1 -based first-line therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Extensive-stage Small-cell Lung Cancer
• Intervention / Treatment: Drug: ivonescimab; Drug: irinotecan liposome

Detailed Description

Patients will receive ivonescimab at 20mg/kg intravenously, on days 1 of every 21-day cycle and irinotecan liposome 56.5mg/m^2 intravenously, on days 1 of every 14-day cycle. Treatment will be discontnued in case of until the toxicity became intolerable, the investigator determined that there was no further clinical benefit (based on a combination of RECIST V1.1 imaging assessment and clinical status), 24 months of treatment was completed, or the study was withdrawn for other reasons.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
      • Principal Investigator: Yun Fan, MD
      • Contact: Yun Fan, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 18 to 75 years old (at the time of inform consent obtained).
2. Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
3. Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system).
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Life expectancy of at least 3 months.
6. ES-SCLC who failed first-line platinum-based chemotherapy with checkpoint inhibitors.
7. At least one measurable tumor lesion according to RECIST v1.1.
8. Adequate organ function.
9. All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.

Exclusion Criteria:

1. Patients with other cancer in 5 years.
2. Undergone anti-angiogenic therapy prior to the first dose of study treatment.
3. Evidence and history of severe bleeding tendency.
4. History of severe active autoimmune disease that has required systemic treatment in the past 2 years, severe drug allergy or have known allergy to any component of the study drugs.
5. Active central nervous system (CNS) metastases.
6. Active infection requiring systemic therapy.
7. Current presence of uncontrolled pleural, pericardial, and peritoneal effusions.
8. Active hepatitis B/C, or HIV infection.
9. History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment.
10. History of allogeneic hematopoietic stem cell transplantation or allogeneic organ transplantation.
11. History of alcohol abuse, psychotropic substance abuse or drug abuse.
12. Pregnant or lactating women.
13. Other conditions considered unsuitable for this study by the investigator.

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: ivonescimab and irinotecan liposome; Subjects receive ivonescimab plus irinotecan liposome until progression.	Drug: ivonescimab; 20mg/kg, IV, D1, Q3W; Other Names: AK112; Drug: irinotecan liposome; 56.5mg/m^2, IV, D1, Q2W; Other Names: Irinotecan liposome injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate（ORR）	Objective response rate (ORR) is defined as the proportion of subjects with complete response (CR) or partial response (PR), based on RECIST v1.1.	Interval between the date of enrollment and the date of death from any cause, up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade 3 or higher adverse events (AEs)	Frequency and severity of adverse events measured according to NCI Common Toxicity Criteria Adverse Event (CTCAE), version 5.0.	Interval between the date of enrollment and the date of death from any cause, up to a maximum of 2 years
Disease control rate (DCR)	DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks), based on RECIST v1.1.	Interval between the date of enrollment and the date of death due to any cause , up to a maximum of approximately 2 years
Duration of Response (DOR)	DOR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST v1.1) or death due to any cause, whichever occurs first.	Interval between the date of enrollment and the date of death from any cause, up to a maximum of 2 years
Progression free survival (PFS)	PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1) assessed by the investigator or death due to any cause (whichever occurs first).	Interval between the date of enrollment and the date of progressive disease, or death due to any cause (whichever occurs first), up to a maximum of 2 years
Overall survival (OS)	OS is the time from the date of randomization or first dosing date to death due to any cause.	Interval between the date of enrollment and the date of death from any cause, up to a maximum of 2 years

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: June 21, 2024
• First Submitted That Met QC Criteria: June 21, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: July 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: IRB-2024-543 (IIT)

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