Study of Glembatumumab Vedotin in gpNMB-Expressing, Advanced or Metastatic SCC of the Lung (PrE0504)
|ClinicalTrials.gov Identifier: NCT02713828|
Recruitment Status : Active, not recruiting
First Posted : March 21, 2016
Last Update Posted : April 27, 2018
Patients with advanced or metastatic, gpNMB-expressing Squamous Cell Carcinoma (SCC) of the lung who have failed a prior platinum-based chemotherapy regimen will receive glembatumumab vedotin.
Glembatumumab vedotin consists of an antibody (a type of human protein) attached to a drug called Monomethyl Auristatin E (MMAE) that can kill cancer cells. Glembatumumab vedotin is intended to work by specifically directing the drug to the cancer cell. It attaches to a molecule on the cancer cell called gpNMB, and then releases the MMAE inside the tumor cell, which in turn causes the cell to die.
The purpose of this study is to see whether glembatumumab vedotin is effective in treating people who have advanced or metastatic squamous cell lung cancer that contains gpNMB, to examine how the body handles the drug and the side effects associated with glembatumumab vedotin.
|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Carcinoma of the Lung||Drug: Phase I: Glembatumumab Vedotin Drug: Phase II: Glembatumumab Vedotin||Phase 1 Phase 2|
Lung cancer is the most frequent cancer in the world, with annual cases worldwide currently estimated at one million and increasing to 10 million by the year 2025. In the United States, despite the declining incidence in white males in recent years, lung cancer is still the second most frequent cancer in both men (next to prostate) and women (next to breast cancer).
This is an open-label, single arm study of glembatumumab vedotin, a fully-human IgG2 monoclonal antibody. The activity of glembatumumab vedotin may be greatest in patients who overexpress the target, gpNMB.
This study will include a dose-escalation phase to determine the maximum safe and tolerated dose. This will be followed by a 2-stage Phase II expansion. During Phase II Stage 1, approximately 20 eligible, treated patients will be enrolled. If ≥ 2 patients achieve a tumor response [Partial Response (PR) or Complete Response (CR)]; an additional 15 eligible, treated patients will be enrolled in Stage 2, for a maximum total of 35 eligible, treated patients.
Glembatumumab vedotin will be administered once every 3 weeks, as a 90-minute intravenous (IV) infusion.
Patients will continue treatment until disease progression or intolerance. Tumor assessments will be performed every six (±1) weeks for six months, and every nine (±2) weeks thereafter, until progression.
A tumor tissue sample (i.e., obtained during a previous procedure or biopsy) will be sent to a central laboratory and tested for gpNMB. Research blood samples will also be required.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Glembatumumab Vedotin in Patients With gpNMB-Expressing, Advanced or Metastatic Squamous Cell Carcinoma of the Lung|
|Study Start Date :||April 10, 2016|
|Estimated Primary Completion Date :||April 2019|
|Estimated Study Completion Date :||August 2019|
Experimental: Phase I: Glembatumumab Vedotin
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Drug: Phase I: Glembatumumab Vedotin
Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
Other Name: CDX-011; CR011-vcMMAE
Experimental: Phase II: Glembatumumab Vedotin
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Maximum Tolerated Dose (MTD) determined in Phase I will be used in Phase II.
Drug: Phase II: Glembatumumab Vedotin
In Stage 1, approximately 20 eligible, treated patients will be enrolled. If ≥ 2 patients achieve a tumor response (Partial Response [PR] or Complete Response [CR]), an additional 15 eligible, treated patients will be enrolled in Stage 2, for a maximum total of 35 eligible, treated patients.
Other Name: CDX-011; CR011-vcMMAE
- Phase I: Number of participants with treatment-related adverse events resulting in dose limiting toxicities (DLTs) as assessed by CTCAE v4.0 [ Time Frame: 12 months ]To determine the Maximum Tolerated Dose (MTD) by number of participants with abnormal laboratory values and/or adverse events related to treatment.
- Phase II: Objective Response Rate (ORR) [ Time Frame: 40 months ]Determine the anti-tumor activity, as assessed by ORR in accordance with RECIST 1.1, of the MTD of glembatumumab vedotin in patients with advanced gpNMB-expressing SCC of the lung.
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. [ Time Frame: 52 months ]To further characterize the safety of glembatumumab vedotin by the number of participants with abnormal laboratory values and/or adverse events related to treatment.
- Duration of Objective Response (DOR) [ Time Frame: 52 months ]DOR assessed in accordance with RECIST 1.1.
- Progression-Free Survival (PFS) [ Time Frame: 52 months ]PFS assessed in accordance with RECIST 1.1.
- Overall Survival (OS) [ Time Frame: 52 months ]OS assessed in accordance with RECIST 1.1.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02713828
|United States, Florida|
|University of Miami Hospital|
|Miami, Florida, United States, 33136|
|United States, Georgia|
|Emory University Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Louisiana|
|Ochsner Medical Center|
|New Orleans, Louisiana, United States, 70121|
|United States, Nebraska|
|Missouri Valley Cancer Consortium|
|Omaha, Nebraska, United States, 68106|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|United States, New York|
|Stony Brook University|
|Stony Brook, New York, United States, 11794-9446|
|United States, Pennsylvania|
|Penn State Hershey Cancer Institute|
|Hershey, Pennsylvania, United States, 17033|
|United States, Texas|
|University of Texas Southwestern Medical Center|
|Dallas, Texas, United States, 75390|
|United States, West Virginia|
|West Virginia University|
|Morgantown, West Virginia, United States, 26506|
|United States, Wisconsin|
|Gundersen Health System|
|La Crosse, Wisconsin, United States, 54601|
|Study Chair:||Rathi Pillai, MD||PrECOG, LLC.|