Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Squamous Cell

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Glembatumumab vedotin

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoconjugates

Immunologic Factors

Antineoplastic Agents, Immunological

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.

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.

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.

Phase I: 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.

Phase II: Glembatumumab Vedotin

Rathi Pillai, MD

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.

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

A Phase I/II Study of Glembatumumab Vedotin in Patients With gpNMB-Expressing, Advanced or Metastatic Squamous Cell Carcinoma of the Lung

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

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.

To further characterize the safety of glembatumumab vedotin by the number of participants with abnormal laboratory values and/or adverse events related to treatment (including Serious Adverse Events and Other Adverse Events).

DOR assessed in accordance with RECIST 1.1.

PFS assessed in accordance with RECIST 1.1.

OS assessed in accordance with RECIST 1.1.

Celldex Therapeutics

PrECOG, LLC.

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.

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.

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.

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.

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

PS 0: Fully active, able to carry on all pre-disease performance without restriction; PS 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g. light house work, office work.

ECOG Performance Status

Prior lines of treatment

The study terminated early during the phase I portion of the trial

Dr Zhuoxin Sun

Phase I: Determine Maximum Tolerated Dose (MTD)

Phase II: Objective Response Rate (ORR)

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

1 patient achieved partial response. The duration of this patient's response is at least 9.4 months, with response ongoing at the time of final report.

Spots Global Cancer Trial Database for phase i: glembatumumab vedotin