Phase II Study of Platinum/Etoposide Plus Ivonescimab for Extensive-Stage Small Cell Lung Cancer

Not Applicable

Not yet recruiting

• Conditions: Extensive Stage Lung Small Cell Cancer
• Interventions: Drug: Ivonescimab 10 mg/kg; Drug: Ivonescimab 20 mg/kg

• Registration Number: NCT07057791
• Lead Sponsor: PrECOG, LLC.

Brief Summary

Eligible untreated participants with Extensive Stage Small Cell Lung Cancer (ES-SCLC) who are ≥ 18 years of age will be randomized to receive ivonescimab 10 milligrams per kilogram (mg/kg) or ivonescimab 20 mg/kg in combination with carboplatin and etoposide.

Ivonescimab is a type of drug called a bispecific antibody. Antibodies are proteins that specifically recognize and bind to other types of proteins called antigens. Antibodies and antigens can work together to help the immune system fight cancer cells. Bispecific antibody, meaning it targets two different molecules at the same time.

Ivonescimab is a new drug that may help the immune system attack cancer cells and may also block certain pathways that cancer uses to grow and spread. This dual action of ivonescimab aims to help the immune system to fight the cancer and also disrupt tumor growth by blocking blood vessel formation that tumors use to grow.

Participants will receive induction with 4 cycles of ivonescimab (dose determined by randomization) with standard of care carboplatin and etoposide followed by maintenance therapy with ivonescimab at the same dose received during induction. Treatment will continue until disease progression, unacceptable toxicity or participant withdrawal.

The purpose of this study is to determine what dose of ivonescimab works best in combination with carboplatin and etoposide chemotherapy in ES-SCLC. We will also examine the side effects, good and bad, associated with ivonescimab.

Detailed Description

Randomized, Phase II, open-label trial designed to determine the optimal dose of ivonescimab with carboplatin and etoposide for a more diverse Western participant population with ES- SCLC based on overall response rate and safety profile of two dose levels of ivonescimab (10 mg/kg versus 20 mg/kg) previously evaluated in the Chinese population.

The simultaneous blockade of vascular endothelial growth factor (VEGF) and Programmed Death-Ligand 1 (PDL-1) by ivonescimab may achieve a higher target binding of VEGF and PD-1 within the tumor microenvironment and produce increased anti-tumor effect with an improved safety profile than administration of anti-PD-(L)1 and anti-VEGF therapies separately.

Participants will be randomized 1:1 to receive ivonescimab 10 mg/kg or 20 mg/kg. Induction treatment will be administered on a 21-day cycle for four cycles with standard of care carboplatin and etoposide.

Following the induction phase, participants will continue maintenance therapy with ivonescimab on a 21-day cycle at the dose received during induction (10 mg/kg or 20 mg/kg). Treatment will be discontinued in all participants who have evidence of progressive disease by Response Criteria Evaluation in Solid Tumors version 1.1 (RECIST v1.1).

Research tumor tissue will be requested at baseline for future research. Research blood samples will also be obtained for future research which may include measuring the level of ivonescimab in the blood and immune responses or antibodies to ivonescimab.

Study Timeline

• Study First Submitted: 2025-06-30
• Study First Submitted QC: 2025-06-30
• Study First Posted: 2025-07-10
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-03
• Last Update Posted: 2025-09-05
• Study Start: 2025-12-01
• Primary Completion: 2027-12
• Study Completion: 2030-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Ivonescimab 10 mg/kg	Ivonescimab 10 mg/kg	Induction with ivonescimab 10 mg/kg, carboplatin and etoposide every 21 days x 4 cycles followed by maintenance ivonescimab 10 mg/kg every 21 days until progression, unacceptable toxicity or participant withdrawal.
Arm B: Ivonescimab 20 mg/kg	Ivonescimab 20 mg/kg	Induction with ivonescimab 20 mg/kg, carboplatin and etoposide every 21 days x 4 cycles followed by maintenance ivonescimab 20 mg/kg every 21 days until progression, unacceptable toxicity or participant withdrawal.

Primary Outcome Measures

Name	Time	Method
Optimal Dose of Ivonescimab in Combination with Carboplatin and Etoposide - Overall Response Rate (ORR)	18 months	Overall Response Rate (ORR) defined as the proportion of participants achieving complete response (CR) or partial response (PR) as best response on treatment based on RECIST v1.1 criteria at each dose level.
Optimal Dose of Ivonescimab in Combination with Carboplatin and Etoposide - Grade 3-5 Treatment-Related Toxicity Rate	18 months	All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE V5.0) that are not resolved in accordance with treatment guidelines will be counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS) of of Ivonescimab in Combination with Carboplatin and Etoposide	24 months	OS based on the Kaplan-Meier method defined as the time from study entry to death or censored at date last known alive.
Progression-Free Survival (PFS) of Ivonescimab in Combination with Carboplatin and Etoposide	18 months	PFS based on the Kaplan-Meier method defined as the duration between randomization and documented disease progression (PD) defined per RECIST 1.1 criteria. or death, or is censored at time of last disease assessment.
Disease Control Rate (DCR) of Ivonescimab in Combination with Carboplatin and Etoposide	18 months	DCR defined as the proportion of participants who achieved a best overall response of complete response (CR), partial response (PR) , or stable disease (SD), as determined by investigator assessment (disease control rate- CR+PR+SD) per RECIST v1.1. Patients who have not progressed by the time of analysis will be censored at the date they are last known to be alive and progression-free.
Duration of Response (DoR) of Ivonescimab in Combination with Carboplatin and Etoposide	18 months	DoR is defined as from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Patients who have not progressed by the time of analysis will be censored at the date they are last known to be alive and progression-free.
Duration of Stable Disease of Ivonescimab in Combination with Carboplatin and Etoposide	18 months	Duration of stable disease is measured from the start of treatment until the criteria for disease progression are met per RECIST v1.1. Patients who have not progressed by the time of analysis will be censored at the date they are last known to be alive and progression-free.