Anti-Mesothelin Antibody Drug Conjugate Anetumab Ravtansine for Mesothelin Expressing Lung Adenocarcinoma

Lung Neoplasms Clinical Trial

Official title: Phase II Trial With Safety Run-in of the Anti-Mesothelin Antibody Drug Conjugate Anetumab Ravtansine for Mesothelin Expressing Lung Adenocarcinoma

Status Terminated

Clinical Trial Summary

Background:

Anetumab ravtansine is a new drug. It kills cancer cells that carry mesothelin. That is a protein on the surface of tumor cells in many types of tumors, including most lung cancers. Researchers want to find a safe dose for the study drug for lung cancer. They want to see if it can shrink tumors in mesothelin-positive lung cancer.

Objectives:

To test the safety and effectiveness of anetumab ravtansine for lung cancer.

Eligibility:

Adults 18 years and older who have lung cancer that has gotten worse on other therapy

Design:

Participants will be screened with:

Medical history

Physical exam

Tumor tissue sample. This can be from a previous procedure.

Blood and urine tests

Heart tests

Scans. For one scan, a small amount of radioactive substance is injected into the blood.

Eye exam

The study will have 21-day cycles.

On day 1 of each cycle, participants will get the study drug through a tube inserted in a vein.

Participants will repeat a heart test in cycles 1 and 2.

They will have blood tests weekly in cycle 1, twice in all other cycles.

They will have scans every 6 weeks for the first 6 months, every 9 weeks until the end of year 2, then every 12 weeks.

Participants will have samples of tumor tissue taken twice.

About 30 days after stopping the study drug, participants will have a follow-up visit. This will include medical history, physical exam, blood and pregnancy tests, and heart and eye tests.

Some will be called a few times a year to discuss their health and treatment.

Clinical Trial Description

Background:

• Lung cancer is the leading cause of cancer-related death worldwide, accounting for more than one million deaths every year.

• Non-small-cell lung cancer (NSCLC) constitutes approximately 85% of lung cancers and about 40% of patients with newly diagnosed NSCLC have advanced disease. The median year overall survival for advanced NSCLC is at least 1 year.

• In recent years, identification of oncogenic alterations such as mutations in epidermal growth factor receptor (EGFR) and anaplastic large-cell lymphoma kinase (ALK) translocations and therapies targeting tumor immune escape mechanisms have led to a substantial improvement in the prognosis of patients with advanced lung cancer;

however, such alterations have been detected in less than half of all advanced NSCLC patients in only a small subset of patients respond to immunotherapeutic interventions available today.

• Anetumab ravtansine (BAY 94-9343) is an antibody-drug conjugate targeting mesothelin, a protein normally present on mesothelial cells. A Phase I trial showed the overall acceptable and manageable safety profile. It is being developed for patients with mesothelin expressing cancers; clinical development is furthest along in mesothelioma where it is in a registration phase II clinical trial.

• National Cancer Institute (NCI) researchers have demonstrated that mesothelin messenger ribonucleic acid (mRNA) and protein are present in a substantial number of lung adenocarcinoma cell lines; mesothelin expression has been observed in over 50% of advanced lung adenocarcinomas by immunohistochemical assessment.

Objectives:

Safety Run-in

-To evaluate safety and tolerability of anetumab ravtansine in patients with previously treated unresectable mesothelin expressing advanced lung adenocarcinoma (stage IIIB or IV).

Phase 2

-To determine the efficacy (objective response rate) of anetumab ravtansine in patients with advanced (Stage IIIb) or metastatic (Stage IV) mesothelin expressing lung adenocarcinoma.

Eligibility:

• Age >18 years.

• Histologically or cytologically confirmed previously treated unresectable mesothelin expressing advanced lung adenocarcinoma (stage IIIB or IV)

• Positive mesothelin expression in the archival tumor tissue, defined as the mesothelin membrane intensity score of 2+ or 3+ (on the 0-3 scale) expressed on the membrane of greater than or equal to 10% of tumor cells.

• Should have received at least one prior platinum based chemotherapy and an immune checkpoint targeted agent. In addition, subjects with epidermal growth factor receptor [EGFR]-mutated and anaplastic lymphoma kinase [ALK]-translocated NSCLC should have received Food and Drug Administration (FDA)-approved targeted therapies as appropriate.

• Normal organ function

Design:

• This is an open label, single center, phase I/II study of anetumab ravtansine in subjects with mesothelin positive lung adenocarcinoma.

• During the safety run-in portion of the study, de-escalating doses will be assessed to determine a recommended phase 2 dose (RP2D).

• During the phase 2 portion of the study, the (RP2D) will be assessed for objective response rate.

• During both portions of the study, anetumab ravtansine will be administered intravenously every 3 weeks until disease progression in the absence of clinical benefit, patient withdrawal or the occurrence of intolerable toxicities.

• Response assessments (imaging) will occur every 6 weeks for the first 6 months, then every 9 weeks until the end of year 2, then every 12 weeks thereafter.

• Up to 12 evaluable patients will be enrolled in the safety run-in portion of the study. Approximately twenty patients, including 6 from the safety run-in portion of the study, will be evaluated in the phase 2 portion of the study. The accrual ceiling will be set at 55 to accommodate screen failures (a 50% failure rate with regard to mesothelin expression) and inevaluable subjects. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Lung Neoplasms

• NCT number: NCT02839681
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 2
• Start date: July 19, 2016
• Completion date: July 25, 2018