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

NCT02839681 | Terminated Phase 2 Results FDA Drug FDA Device

• 2 other identifiers: 16014516-C-0145
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lung Neoplasms

Keywords

Lung Adenocarcinoma; Immunotoxin; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D)

  The highest dose tested at which no more than 1 dose limiting toxicity occurs. A dose limiting toxicity is defined as any treatment emergent adverse event (TEAE) (i.e., absolute neutrophil count \<500/mm\^3 for ≥7 days) occurring during Cycle 1 and regarded to be at least possibly related to anetumab ravtansine.

  21 days after initiation of study therapy

• Proportion of Subjects Who Experienced a Partial or Complete Response

  Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). A complete response is disappearance of all target lesions. A partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

  6 weeks

Secondary Outcomes (4)

• Progression Free Survival

  At Disease Progression, approximately 6 weeks.

• Duration of Response

  At Disease Progression, approximately 6 weeks from start of treatment

• Overall Survival

  At Death, an average of 7.5 weeks after start of first cycle for both patients.

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Participants on the Safety run-in phase was assessed for approximately two months and 5 days.

Study Arms (2)

1/Safety Run-in Arm

EXPERIMENTAL

Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study

Drug: Anetumab Ravtansine; Device: Blood test

2/Phase 2 Arm

EXPERIMENTAL

Subjects will be dosed with anetumab ravtansine at the recommended phase 2 dose (dose level 1 if no more than 1 dose limiting toxicity (DLT) occurred in the safety run-in arm, or at dose level -1 otherwise)

Drug: Anetumab Ravtansine; Device: Blood test

Interventions

Anetumab Ravtansine DRUG

Administered intravenously (IV) every 3 weeks

Also known as: BAY 94-9343

1/Safety Run-in Arm; 2/Phase 2 Arm

Blood test DEVICE

Research blood test for eligibility

1/Safety Run-in Arm; 2/Phase 2 Arm

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Subjects who have a previous or concurrent cancer that is distinct in primary site or histology from lung adenocarcinoma, except cervical carcinoma in situ, treated basal cell carcinoma, superficial noninvasive bladder tumors or any previous cancer curatively treated \<2 years before the start of study treatment.
• Subjects who have a history or current evidence of bleeding disorder, i.e. any hemorrhage/bleeding event of Common Terminology Criteria in Adverse Events (CTCAE) Grade greater than or equal to 2 within 4 weeks before the start of study treatment.
• History of symptomatic metastatic brain or meningeal tumors unless the subject is \> 3 months from definitive therapy and has no evidence of tumor growth on an imaging study within 2 weeks prior to study entry. Subjects with brain metastases must not be undergoing acute corticosteroid therapy or steroid taper. Chronic steroid therapy is acceptable provided that the dose is stable for one month prior to screening.
• Subjects who have a history or current evidence of uncontrolled cardiovascular disease including but not limited to the following conditions:
• Congestive heart failure of New York Heart Association (NYHA) Class III or IV
• Unstable angina (symptoms of angina at rest) or new-onset angina within \<3 months before the start of study treatment.
• Arterial thrombosis, deep vein thrombosis, or pulmonary embolism within \<3 months before the start of study treatment.
• Myocardial infarction or stroke within \<3 months before the start of study treatment.
• Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade greater than or equal to 2) or pleural effusion (CTCAE Grade greater than or equal to 2)
• Cardiac arrhythmia requiring anti-arrhythmic therapy. Subjects receiving digoxin, calcium channel blockers except verapamil, or beta-adrenergic blockers except propranolol are eligible at the investigators discretion if the dose has been stable for at least 2 weeks before the start of study treatment. Subjects with sinus arrhythmia and infrequent premature ventricular contractions are eligible at the investigators discretion.
• Subjects who have a left ventricular ejection fraction (LVEF) \<50%, as assessed by echocardiogram performed at screening.
• Subjects who have a corrected Q wave, T wave (QT) (corrected QT interval by Fredericia (QTcF)) interval \>480 ms (CTCAE Grade \>1) determined by the electrocardiogram (ECG) recorders algorithm on the screening ECG.
• Subjects who have a history or current evidence of uncontrolled hypertension defined as systolic blood pressure \>150 mmHg or diastolic blood pressure \>95 mmHg at screening despite optimal medical management. Subjects with a history of mild to moderate
• hypertension are eligible at the investigator s discretion if the hypertension is adequately controlled by antihypertensive treatment used at a stable dose for at least 2 weeks before the start of study treatment.
• Subjects who have a heart rate greater than or equal to 100 beats per minute (bpm) or less than or equal to 45 bpm determined by the ECG recorder s algorithm on the screening ECG.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Adenocarcinoma of Lung

Interventions

anetumab ravtansine; Hematologic Tests

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Results Point of Contact

• Title: Dr. Raffit Hassan
• Organization: National Cancer Institute

raffit_hassan@nih.gov

240-760-6232

Study Officials

• Raffit Hassan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: July 21, 2016
• Study Start: July 19, 2016
• Primary Completion: June 12, 2018
• Study Completion: July 25, 2018
• Last Updated: May 21, 2019
• Results First Posted: May 21, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)