Study of Glembatumumab Vedotin in gpNMB-Expressing, Advanced or Metastatic SCC of the Lung

NCT02713828 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: PrE0504CDX011-54
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of the Lung

Keywords

gpNMB-Expressing Squamous Cell Carcinoma of the Lung; Stage IIIb; Stage IV; Advanced Squamous Cell Cancer of the Lung; Metastatic Squamous Cell Cancer of the Lung; gpNMB-Expressing; Glembatumumab Vedotin

Outcome Measures

Primary Outcomes (2)

• Phase I: Determine Maximum Tolerated Dose (MTD)

  To determine the Maximum Tolerated Dose (MTD) by number of participants with DLTs.

  42 (±3) days

• Phase II: Objective Response Rate (ORR)

  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.

  40 months

Secondary Outcomes (4)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0.

  23 months

• Duration of Objective Response (DOR)

  23 months

• Progression-Free Survival (PFS)

  23 months

• Overall Survival (OS)

  23 months

Study Arms (2)

Phase I: Glembatumumab Vedotin

EXPERIMENTAL

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

Phase II: Glembatumumab Vedotin

EXPERIMENTAL

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

Interventions

Phase I: Glembatumumab Vedotin DRUG

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.

Also known as: CDX-011; CR011-vcMMAE

Phase I: Glembatumumab Vedotin

Phase II: Glembatumumab Vedotin DRUG

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.

Also known as: CDX-011; CR011-vcMMAE

Phase II: Glembatumumab Vedotin

Eligibility Criteria

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

You may qualify if:

• Read, understood, and provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures.
• Male or female patients with metastatic, histologically- or cytologically-confirmed unresectable Stage IIIB or IV non-small cell lung cancer (NSCLC) of squamous histology (Staging per American Joint Committee on Cancer \[AJCC\], Edition 7). Mixed histology adenosquamous NSCLC will also be permitted.
• Experienced progression/recurrence of disease during or subsequent to the most recent anti-cancer regimen.
• Any number of prior lines of systemic therapy may have been received for advanced (recurrent, locally advanced, or metastatic) SCC of the lung, but at least one must have been a platinum-based chemotherapy regimen. Platinum therapy may be given on-label or as part of a clinical trial.
• Lung cancer confirmed to express gpNMB, as assessed by immunohistochemistry at a central lab (using expression in ≥ 5% of tumor epithelial cells as a cut-off for positivity). This can be tested on archived tissue if available, although preferred tumor specimen is a biopsy after the most recent therapy.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
• Measurable disease by RECIST 1.1 criteria. Target lesions selected for tumor measurements should be those where surgical resection or radiation are not indicated or anticipated.
• Resolution of all toxicities related to prior therapies to ≤ NCI-CTCAE Grade 1 severity, except for alopecia, vitiligo, or endocrinopathies on replacement therapy.
• Adequate bone marrow function as assessed by absolute neutrophil count (ANC) ≥ 1500/mm3; hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100,000/mm3.
• Adequate renal function as assessed by serum creatinine ≤ 2.0 mg/dL; or calculated or 24-hour urine creatinine clearance \>40 mL/min.
• Serum albumin ≥ 3 g/dL.
• Adequate liver function as assessed by total bilirubin ≤ 1.5x upper limit of normal (ULN), and alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5x ULN (≤ 5.0x ULN in the case of liver metastases). Patients with known Gilbert's syndrome may be enrolled with total bilirubin ≤ 3.0 mg/dL.
• Both male and female patients of childbearing potential enrolled in this trial must use adequate birth control measures during the course of the trial and for at least one month after discontinuing study drug.
• Willing to provide blood samples for research purposes.

You may not qualify if:

• Received glembatumumab vedotin (CR011-vcMMAE; CDX-011) or other MMAE-containing agents previously.
• Chemotherapy within 21 days or at least 5 half-lives prior to the planned start of study treatment; radiation outside the thorax within 14 days prior to the planned start of study treatment or thoracic radiation; antibody based therapy or investigational therapy within 28 days prior to the planned start of study treatment.
• Neuropathy \>NCI-CTCAE Grade 1.
• Subjects with a history of allergic reactions attributed to compounds of similar composition to dolastatin or auristatin. Compounds of similar composition include Auristatin PHE as an anti-fungal agent, Auristatin PE (TZT-1027, Soblidotin, NSC-654663) as an anti-tumor agent and Symplostatin 1 as an anti-tumor agent.
• Known brain metastases, unless previously treated and patients are neurologically returned to baseline except for residual signs and symptoms related to Central Nervous System (CNS) treatment and CNS lesions are not progressive in size and number for 4 weeks.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, and congestive heart failure related to primary cardiac disease, a history of a serious uncontrollable arrhythmia despite treatment, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry.
• Subjects on immunosuppressive medications such as azathioprine, mycophenolate mofetil, cyclosporine or require chronic corticosteroid use (defined as ≥ 3 months of prednisone dose equivalent of ≥ 10 mg).
• The MMAE component of glembatumumab vedotin is primarily metabolized by CYP3A. Patients taking strong CYP3A inhibitor and inducers are excluded in Phase I (the dose escalation portion), to minimize the effect of these modulators on exposure, tolerability and dose selection.
• History of other malignancy except for adequately treated basal or squamous cell skin cancer, curatively treated in situ disease, or any other cancer from which the patient has been disease-free for ≥ 2 years.
• Pregnant or breast-feeding women.
• Subjects must not be on home oxygen therapy (intermittent or continuous).
• Any underlying medical condition that, in the Investigator's opinion, will make the administration of study treatment hazardous to the patient, or would obscure the interpretation of adverse events.

Sponsors & Collaborators

• PrECOG, LLC.: lead
• Celldex Therapeutics: collaborator

Study Sites (10)

University of Miami Hospital

Miami, Florida, 33136, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Stony Brook University

Stony Brook, New York, 11794-9446, United States

Location

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Gundersen Health System

La Crosse, Wisconsin, 54601, United States

Location

MeSH Terms

Interventions

glembatumumab vedotin; CR011-vcMMAE

Results Point of Contact

• Title: Dr Zhuoxin Sun
• Organization: ECOG Stats Center

zhuoxin@jimmy.harvard.edu

617-632-3012

Study Officials

• Rathi Pillai, MD

  PrECOG, LLC.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 21, 2016
• Study Start: April 10, 2016
• Primary Completion: May 29, 2018
• Study Completion: September 26, 2018
• Last Updated: July 16, 2019
• Results First Posted: July 16, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)