Testing the Combination of MLN4924 (Pevonedistat), Carboplatin, and Paclitaxel in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) Who Have Previously Been Treated With Immunotherapy

NCT03965689 | Active Not Recruiting Phase 2 Results FDA Drug

• 5 other identifiers: NCI-2019-03212NCI1026610266UM1CA186691UM1CA186716
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 10

Brief Summary

This phase II trial studies how well MLN4924 (pevonedistat), carboplatin, and paclitaxel work in treating patients with stage IIIB or IV non-small cell lung cancer. Pevonedistat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as carboplatin and paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pevonedistat together with carboplatin and paclitaxel may work better in treating patients with non-small cell lung cancer when compared with other standard chemotherapy drugs.

Conditions

Stage IV Lung Cancer AJCC v8; Metastatic Lung Non-Squamous Non-Small Cell Carcinoma; Metastatic Lung Non-Small Cell Squamous Carcinoma; Stage IIIB Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Unresectable Lung Non-Small Cell Carcinoma; Unresectable Lung Non-Squamous Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Overall Response

  Response will be evaluated at the time all participants completed treatment and using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Patients will be re-evaluated for response every 6 weeks. Overall response is the best response achieved during the study. Complete response (CR) is the disappearance of all lesions; Partial response (PR) is a \>= 30% decrease in the sum of the target lesions; Progressive disease (PD) is a \>= 20% increase in the sum of the lesions; Stable disease (SD) is between a 20 % increase and 30% decrease in the sum of the lesions.

  Up to 2.5 years

Secondary Outcomes (3)

• Duration of Progression Free Survival (PFS)

  Up to 2.5 years

• Overall Survival (OS)

  Up to 2.5 years

• Number of Participants Reporting Grade 3, 4, and 5 Adverse Events

  1 year, on average

Other Outcomes (16)

• NQO1 Expression Levels

  Day 1 pre-treatment and 6 hours post-infusion

• SLC7A11 Expression Levels

  Day 1 pre-treatment and 6 hours post-infusion

• NAE1 Expression Levels

  Pre-treatment and 6 hours post-infusion on cycle 1, day 1

Study Arms (1)

Treatment (paclitaxel, carboplatin, pevonedistat)

EXPERIMENTAL

Patients receive paclitaxel IV over 3 hours on day 1, carboplatin IV over 30-60 minutes on day 1, and pevonedistat IV over 1 hour on days 1, 3, and 5. Treatment repeats every 21 days for at least 4 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Drug: Paclitaxel; Drug: Pevonedistat

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (paclitaxel, carboplatin, pevonedistat)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (paclitaxel, carboplatin, pevonedistat)

Pevonedistat DRUG

Given IV

Also known as: MLN4924, Nedd8-Activating Enzyme Inhibitor MLN4924

Treatment (paclitaxel, carboplatin, pevonedistat)

Eligibility Criteria

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

You may qualify if:

• Patients must be \>= 18 years old. Because no dosing or adverse event (AE) data are currently available on the use of MLN4924 (pevonedistat) in combination with carboplatin and paclitaxel in patients \< 18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
• Patients must have histologically confirmed stage IIIB or IV NSCLC (squamous or nonsquamous) that is metastatic or unresectable.
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Patients must have progressed on prior treatment with checkpoint inhibitor (PD-1/PD-L1 inhibitors) either as a single-agent therapy or in combination, as below. Patients will be eligible if there is a contra-indication to checkpoint inhibitor therapy.
• Patients who have progressed after receiving a checkpoint inhibitor in combination with a platinum-based doublet, as first-line treatment for NSCLC.
• Patients who have progressed on checkpoint inhibitor as second-line therapy, after receiving a platinum-based doublet as first-line therapy.
• Patients who have progressed on platinum-based doublet as second-line therapy, after receiving a checkpoint inhibitor as first-line therapy.
• Patients must have disease progression on or after platinum-based chemotherapy for metastatic disease or within 6 months of completion of platinum-based chemotherapy administration as adjuvant/neoadjuvant chemotherapy or concurrent chemoradiation.
• Absolute neutrophil count \>= 1,500/mcL.
• Platelet count \>= 150,000/mcL.
• Total bilirubin =\< 1 x institutional upper limit of normal (ULN). Patients with Gilbert's syndrome may enroll if direct bilirubin =\< 1.5 x institutional ULN.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN. Patients with metastatic liver disease may enroll if =\< 5 x ULN.
• Glomerular filtration rate (GFR) \> 30 mL/min/1.73 m\^2.
• Known human immunodeficiency virus (HIV) positive patients who meet the following criteria will be considered eligible:
• CD4 count \> 350 cells/mm\^3.

You may not qualify if:

• Patients who have not recovered from AEs due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia and neuropathy.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN4924 (pevonedistat), carboplatin, or paclitaxel.
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Patients with uncontrolled intercurrent illness.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because MLN4924 (pevonedistat), carboplatin, and paclitaxel have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MLN4924 (pevonedistat), breastfeeding must be discontinued if the mother is treated with MLN4924 (pevonedistat). These potential risks may also apply to other agents used in this study.
• Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
• Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).
• Known cardiopulmonary disease defined as:
• Unstable angina;
• Congestive heart failure (New York Heart Association \[NYHA\] class III or IV;);
• Myocardial infarction within 6 months prior to first dose (patients who had ischemic heart disease such as acute coronary syndrome \[ACS\], myocardial infarction, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll);
• Symptomatic cardiomyopathy;
• Clinically significant arrhythmia:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (10)

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Moffitt Cancer Center-International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, 33612, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Carboplatin; Paclitaxel; Taxes; pevonedistat

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Grants Administrative Manager
• Organization: Johns Hopkins University/SKCCC

jmurra33@jhmi.edu

4439273568

Study Officials

• Ticiana A Leal

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: May 29, 2019
• Study Start: April 16, 2020
• Primary Completion: September 7, 2022
• Study Completion (Estimated): March 20, 2027
• Last Updated: April 13, 2026
• Results First Posted: December 15, 2023

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (10)