Ipilimumab and Nivolumab in Recurrent Extensive Stage Small Cell Lung Cancer After Receiving Platinum-based Chemotherapy

Phase 2

Active, not recruiting

• Conditions: Small Cell Lung Cancer
• Interventions: Drug: Combination immunotherapy with Ipilimumab and Nivolumab

• Registration Number: NCT03670056
• Lead Sponsor: Yale University

Brief Summary

This is a pilot study of patients who previously received platinum chemotherapy with recurrent SCLC to evaluate the change in the ratio of intratumoral Teff/Treg cells and clinical benefit of treatment with nivolumab and ipilimumab.

Detailed Description

The primary objective of this study is t assess whether the change in the ratio of effector T cells (Teff) to regulatory T cells (Treg), i.e. CD8 positive/FoxP3 expressing CD4 T cells, between pre- and on- treatment biopsies, will predict clinical response in patients with recurrent SCLC treated with combination therapy with nivolumab and ipilimumab.

Secondary objectives of the study include: to determine the objective response rate per RECIST 1.1 and immune-related response criteria, duration of response, progression free survival, and overall survival with nivolumab and ipilimumab in patients with recurrent SCLC; to evaluate changes in the tumor immune microenvironment and blood after treatment with ipilimumab and nivolumab; and to evaluate circulating tumor DNA (ctDNA) as a marker for response to therapy.

Study Timeline

• Study First Submitted: 2018-09-11
• Study First Submitted QC: 2018-09-11
• Study First Posted: 2018-09-13
• Study Start: 2018-12-06
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-07
• Last Update Posted: 2025-01-09
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nivolumab and Ipilimumab	Combination immunotherapy with Ipilimumab and Nivolumab	Patients will be treated with nivolumab 1 mg/kg and ipilimumab 3 mg/kg, starting on Day 1. Patients will receive 4 doses of each nivolumab and ipilimumab and then will receive nivolumab 240 mg starting week 13 (day 85) every 2 weeks until progression, unacceptable toxicity, withdrawal of consent, or the study ends, whichever occurs first.

Primary Outcome Measures

Name	Time	Method
Change in the ratio of Teff/Treg cells	Up to 24 months	The primary analysis will use the nonparametric Mann-Whitney sign test to compare the change in the ratio of Teff/Treg cells in those patients who respond or not to treatment. This test compares the rate of response in those with above and below Teff/Treg ratio.

Secondary Outcome Measures

Name	Time	Method
Response rate	Up to 24 months	Objective response is defined as a complete or partial response, as determined by investigator assessment using RECIST v1.1 and immune-related response criteria (irRC) . Response will be confirmed by repeat assessments ≥4 weeks after initial documentation. Patients not meeting these criteria, including patients without any post baseline tumor assessment, will be considered non-responders in the analysis of objective response.
Duration of response	Up to 24 months	Duration of response is defined as the time from the initial complete or partial response to the time of disease progression or death, whichever occurs first. If a patient does not experience death or disease progression before the end of the study, duration of response will be censored at the day of the last tumor assessment. If no tumor assessments were performed after the date of the first occurrence of a complete or partial response, duration of objective response will be censored at the date of the first occurrence of a complete or partial response plus 1 day.
Progression-free survival	Up to 24 months	Progression-free survival (PFS) is defined as the time from the first day of treatment until progression of disease using RECIST v1.1 and immune-related response criteria (irRC) . If a patient has not experienced progressive disease or death, PFS will be censored at the day of the last tumor assessment. Patients with no post baseline tumor assessments will be censored at the date of first study treatment plus 1 day.

Trial Locations

Locations (1)

Yale University, Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States