A Study of the Safety and Pharmacokinetics (PK) of MEHD7945A in Participants With Locally Advanced or Metastatic Epithelial Tumors

NCT01207323 | Completed Phase 1

• 3 other identifiers: DAF4873gGO007652010-022217-26
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a Phase I, multicenter, open-label study of MEHD7945A in participants with incurable, locally advanced, or metastatic epithelial malignancies that have progressed despite standard therapy or for which no standard therapy exists. The study will be conducted in two stages: a dose escalation stage and an expansion stage. The dose-escalation stage is designed to evaluate the safety, tolerability, and PK of MEHD7945A administered (at five dose levels from 1 to 30 milligrams per kilogram \[mg/kg\]) every 2 week (Q2W). An expansion stage will be initiated after establishment of maximum tolerated dose (MTD) in dose escalation stage. Participants with refractory or recurrent metastatic colorectal cancer (CRC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and pancreatic cancer will be enrolled in an expansion stage to better characterize the safety, tolerability, PK and preliminary assessment of the anti-tumor activity of MEHD7945A.

Conditions

Epithelial Tumors, Malignant

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With Dose-Limiting Toxicities (DLTs) of MEHD7945A

  Days 1-28

• Maximum Tolerated Dose (MTD) of MEHD7945A

  Days 1-28

• Percentage of Participants With Adverse Events

  Baseline up to approximately 6.75 years

• Percentage of Participants With Anti-MEHD7945A Antibodies

  Baseline up to approximately 6.75 years (assessed at predose [0 to 4 hours {Hr}] on Day 1 [D1] of Cycles [Cy] 1, 2, 4 [1 Cycle: 14 days], at the study completion/early termination (ET) visit [up to approximately 6.75 years])

Secondary Outcomes (11)

• Area Under the Concentration-Time Curve (AUC) of MEHD7945A

  Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)

• Maximum Serum Concentration (Cmax) of MEHD7945A

  Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)

• Minimum (Trough) Concentration (Cmin) of MEHD7945A

  Predose (0 to 4 hours) on D1 of Cy1,2,3,4,6, every 4 Cy thereafter (up to Cy16 ); study completion/ET (up to approximately 6.75 years) (Cy=14 days)

• Clearance (Cl) of MEHD7945A

  Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)

• Volume of Distribution at Steady State (Vss) of MEHD7945A

  Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)

Study Arms (2)

Dose Escalation (MEHD7945A)

EXPERIMENTAL

Participants will receive intravenous (IV) infusion of MEHD7945A in escalating doses Q2W until MTD is reached or up to disease progression as determined by the investigator, intolerable toxicity, withdrawal of consent, or death, whichever occurs first. Approximately 5 dose levels between 1 and 30 mg/kg will be evaluated.

Drug: MEHD7945A

Dose Expansion (MEHD7945A)

EXPERIMENTAL

Participants will receive IV infusion of MEHD7945A Q2W at or below the MTD (decided from dose escalation part) up to disease progression as determined by the investigator, intolerable toxicity, withdrawal of consent, or death, whichever occurs first.

Drug: MEHD7945A

Interventions

MEHD7945A DRUG

MEHD7945A will be administered as specified in the individual arms.

Dose Escalation (MEHD7945A); Dose Expansion (MEHD7945A)

Eligibility Criteria

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

You may qualify if:

• Life expectancy greater than or equal to (\>/=) 12 weeks
• Availability and willingness to provide sufficient tumor tissue sample for testing
• Dose-escalation stage: Participants with histologically documented incurable, locally advanced, or metastatic epithelial malignancy that has progressed despite standard therapy or for which no standard therapy exists
• Expansion stage: Participants with one of the following epithelial, histologically-documented, incurable, locally advanced, or metastatic tumor that has progressed despite standard therapy or for which no standard therapy exists: CRC, NSCLC, HNSCC, or pancreatic cancer
• Use of an effective means of contraception (e.g., abstinence, hormonal or double barrier method, surgically sterilized partner) for men and women of childbearing potential while enrolled in the study

You may not qualify if:

• Less than (\<) 4 weeks since the last anti-tumor therapy prior to Day 1 of study treatment
• Major surgical procedure within 4 weeks prior to Cycle 1, Day 1
• Leptomeningeal disease as the only manifestation of the current malignancy
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs
• Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
• Current severe, uncontrolled systemic disease
• History of cardiac heart failure of any New York Heart Association criteria or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction within 6 months before Cycle 1, Day 1, or history of unstable angina
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• History of interstitial lung disease
• History of severe allergic or hypersensitivity reaction to other therapeutic antibodies that required discontinuation of therapy
• Known human immunodeficiency virus (HIV) infection
• Primary central nervous system (CNS) malignancy or untreated/active CNS metastases
• Significant traumatic injury within 4 weeks before Cycle 1, Day 1

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (6)

Uni of Colorado Cancer Center; Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital.

Boston, Massachusetts, 02114, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Carcinoma

Interventions

MEHD7945A

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Andrea Pirzkall, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 20, 2010
• First Posted: September 22, 2010
• Study Start: November 9, 2010
• Primary Completion: December 3, 2013
• Study Completion: April 23, 2018
• Last Updated: May 1, 2018

Record last verified: 2018-04

Locations

ES (3); US (3)