Phase II Clinical Trial of NIVO-IPI-TAXANE in Untreated Metastatic NSCLC

NCT03573947 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00092210
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, non-randomized, phase II clinical research study designed to assess the safety and efficacy of nivolumab and ipilimumab in combination with paclitaxel in patients with treatment naïve NSCLC.

Conditions

Non-small Cell Lung Cancer

Keywords

Stage IV Non-Small Cell Lung Cancer; nivolumab; ipilimumab; paclitaxel; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors RECIST 1.1 (Brand Name) or Death, Whichever Occurs First

  Progression-free survival (PFS) will be defined as the time from first dosing date to the date of the first documented tumor progression determined by the investigator using RECIST 1.1 or death, whichever occurs first

  up to 4 years

Secondary Outcomes (2)

• Description of the Safety and Adverse Events of the Combination Nivolumab, Ipilimumab, and Paclitaxel in Untreated, Metastatic NSCLC.

  up to 4 years

• Estimate the Overall Response Rate With the Study Combination.

  up to 4 years

Study Arms (1)

nivolumab, ipilimumab and paclitaxel

EXPERIMENTAL

patients will be treated with nivolumab and ipilimumab in combination with weekly paclitaxel days 1 and 8 every 21 days until they experience unacceptable drug-related toxicity, disease progression or 24 months. The dosing regimen will be: nivolumab 360 mg every 3 weeks, ipilimumab 1 mg/kg every 6 weeks, and paclitaxel 80 mg/m2 on days 1 and 8 of 1 21 day treatment cycle. Paclitaxel would be stopped after a total of 4-6 cycles of treatment.

Drug: Nivolumab; Drug: Ipilimumab; Drug: Paclitaxel

Interventions

Nivolumab DRUG

360 mg intravenously every 3 weeks

Also known as: Opdivo

nivolumab, ipilimumab and paclitaxel

Ipilimumab DRUG

1 mg/kg intravenously over 30 minutes

Also known as: Yervoy

nivolumab, ipilimumab and paclitaxel

Paclitaxel DRUG

80 mg/m2 on days 1 and 8 of every 21-day treatment cycle

Also known as: Taxol

nivolumab, ipilimumab and paclitaxel

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed Stage IV or recurrent Non-small cell lung cancer squamous or non-squamous histology (Stage IV as diagnosed using the 7th edition of Lung Cancer Stage Classification), with no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease. Prior adjuvant chemotherapy, neoadjuvant chemotherapy, or chemoradiotherapy is permitted as long as the last administration of the prior regimen occurred at least 6 months prior to study enrollment. Patients with EGFR, ALK, or ROS1 alterations must have received one prior TKI.
• A core needle biopsy or surgical specimen must be available for submission.
• At least one site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 that has not been previously irradiated; if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Age ≥ 18 years with ability and willingness to provide informed consent.
• ECOG performance status 0 or 1.
• Negative pregnancy test done ≤72 hours (or per institutional policy) prior to treatment, for women of childbearing potential only. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
• Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Men and women of childbearing potential must agree to use medically accepted barrier methods of contraception (e.g. male or female condom) at the time of pregnancy test (women of childbearing potential only), during the course of the study and for 90 days after the last dose of study drug, even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of study and for 90 days after the last dose of study drug.
• A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy.
• Provision of written informed consent including HIPAA according to institutional guidelines prior to any study-specific procedures
• Patients must agree to research blood sampling to participate in study;
• Adequate organ and marrow function as defined by the following:
• Creatinine clearance ≥ 50 cc/min or serum Cr \< 1.5 x institutional ULN

You may not qualify if:

• Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy and must have received treatment with at least one prior tyrosine kinase inhibitor (TKI).
• Subjects with known ALK or ROS1 translocations which are sensitive to available targeted inhibitor therapy must have received treatment with at least one prior TKI.
• Radiation therapy within 14 days prior to day 1 of study drug.
• Experimental agents within 28 days prior to day 1 of study drug.
• Intolerance of nivolumab or other PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents.
• Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone \< 10 mg daily (or equivalent).
• History of interstitial pneumonitis from any cause.
• Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study, including impaired heart function or clinically significant heart disease.
• Pregnant or breast feeding.
• Not willing to use an effective method of birth control medically accepted barrier methods of contraception (e.g. male or female condom) at the time of pregnancy test (women of childbearing potential only), during the course of the study and for 90 days after the last dose of study drug.
• Current use of medications specified by the protocol as prohibited for administration in combination with the study drugs. This includes patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to day 1 of study drug. Inhaled or topical steroids and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment on day 1 of study drug. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• Known active CNS metastases which are symptomatic. Eligible if metastases have been locally treated 14 days prior to cycle 1 day 1, are clinically controlled, or asymptomatic on cycle 1 day
• Steroid dose must be equivalent of \<10 mg prednisone daily or equivalent dose steroid. Untreated, asymptomatic brain metastases allowed if subject does not require corticosteroids or anticonvulsant therapy.
• History of myocardial infarction, NYHA class III or IV congestive heart failure, or unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment.

Sponsors & Collaborators

• Jeffrey Clarke: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Ipilimumab; Paclitaxel

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. Jeffrey Clarke
• Organization: Duke Cancer Institute

jeffrey.clarke@duke.edu

9196819509

Study Officials

• Jeffrey Clarke, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Asst. Prof. of Medicine

Study Record Dates

• First Submitted: June 19, 2018
• First Posted: June 29, 2018
• Study Start: October 2, 2018
• Primary Completion: March 12, 2023
• Study Completion: June 15, 2023
• Last Updated: October 14, 2025
• Results First Posted: October 14, 2025

Record last verified: 2025-09

Locations

US (1)