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

NCT03670056 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2000023361CA209-9YT
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Small Cell Lung Cancer

Keywords

combination immunotherapy; platinum-based chemotherapy

Outcome Measures

Primary Outcomes (1)

• Change in the ratio of Teff/Treg cells

  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.

  Up to 24 months

Secondary Outcomes (3)

• Response rate

  Up to 24 months

• Duration of response

  Up to 24 months

• Progression-free survival

  Up to 24 months

Other Outcomes (2)

• Change in ctDNA

  Up to 24 months

• Change in tumor microenvironment

  Up to 24 months

Study Arms (1)

Nivolumab and Ipilimumab

EXPERIMENTAL

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.

Drug: Combination immunotherapy with Ipilimumab and Nivolumab

Interventions

Combination immunotherapy with Ipilimumab and Nivolumab DRUG

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.

Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with an active autoimmune disease requiring systemic treatment within the past 3 months, or a syndrome that requires systemic steroids greater than dexamethasone 2 mg daily (or equivalent) or immunosuppressive agents within the past 3 months will be ineligible. Patients with a documented history of severe autoimmune disease but have been off of steroids and immunosuppressive agents for greater than 3 months, or only require intermittent steroid bursts may be eligible following discussion and approval from the Principal Investigator. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects who require intermittent use of inhaled steroids or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement, or psoriasis not requiring systemic therapy (within the past 3 years) or Type 1 diabetes on stable insulin will not be excluded from the study
• Histologically or cytologically documented Extensive Stage Small Cell Lung Cancer with documented disease progression after at least one prior systemic regimen, including one platinum-based regimen, with progression of disease on or after their most recent therapy. Patients previously diagnosed with limited stage Small Cell Lung Cancer treated with concurrent chemoradiation with a platinum doublet now diagnosed with recurrent extensive disease are eligible.
• ECOG performance status of 0 to 2
• Measurable disease with at least one tumor site amenable to biopsy
• Patients may have untreated asymptomatic Central Nervous System (CNS) metastases or treated CNS metastases if they are not currently receiving corticosteroids greater than dexamethasone 2 mg daily or equivalent for 7 days prior to the first dose of study drug. Patients should have completed stereotactic radiation or whole-brain radiation at least 2 weeks prior to Cycle 1, Day 1

You may not qualify if:

• Patients with an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids \> dexamethasone 2 mg daily (or equivalent dose of other corticosteroids) or other immunosuppressive agents.
• Treatment with systemic immunosuppressive medications including but not limited to, dexamethasone at doses \> 2 mg or equivalent dose of other corticosteroids, cyclophosphamide, tacrolimus, sirolimus, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor (anti-TNF) agents within 2 weeks prior to initiation of trial therapy. Inhaled or topically applied steroids, and acute and chronic standard-dose NSAIDs are permitted. Replacement steroids are also permitted.
• Prior treatment with anti-CTLA4 antibodies. Prior anti-PD1 or anti-PDL1 therapy is allowed.
• Symptomatic untreated CNS metastases. Patients with asymptomatic CNS metastases are eligible. Patients with symptomatic brain metastases are eligible, provided they meet all of the following criteria:
• Completed stereotactic radiosurgery or whole- brain radiation at least 2 weeks prior to Cycle 1, Day 1.
• No evidence of interim progression between the completion of CNS-directed therapy and the start of trial therapy.
• No ongoing requirement for steroids greater than dexamethasone 2 mg daily (or equivalent dose of other corticosteroids) as therapy for CNS disease; anticonvulsants at a stable dose are allowed.
• History of leptomeningeal carcinomatosis.
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Any systemic anti-cancer chemotherapy, within 21 days prior to initiation of study treatment.
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 21 days prior to enrollment.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
• Major surgery or traumatic injury within 4 weeks of starting study drug.
• \- Women who are pregnant or lactating.
• \- Known infection with HIV, HBV or HCV. Patients with prior exposure to hepatitis, but no evidence of active or chronic infection, may be eligible.

Sponsors & Collaborators

• Yale University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Yale University, Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Anne Chiang, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: September 13, 2018
• Study Start: December 6, 2018
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)