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

A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MEHD7945A Administered Intravenously to Patients With Locally Advanced or Metastatic Epithelial Tumors

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.

Study Overview

• Status: Completed
• Conditions: Epithelial Tumors, Malignant
• Intervention / Treatment: Drug: MEHD7945A

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Madrid, Spain, 28050
    • HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Uni of Colorado Cancer Center; Anschutz Cancer Pavilion
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital.
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (MEHD7945A); 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; MEHD7945A will be administered as specified in the individual arms.
Experimental: Dose Expansion (MEHD7945A); 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; MEHD7945A will be administered as specified in the individual arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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)
Half-Life (t1/2) 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)
Accumulation Ratio 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)
Recommended Phase 2 Dose (RP2D) of MEHD7945A	Days 1-28
Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0)	From the first study treatment (Cy1 D1, 1 Cy=14 days) to first occurrence of progression or death within 60 days of the last administration of study drug, whichever occurs first (up to approximately 6.75 years)
Duration of Objective Response (CR or PR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0)	First occurrence of a documented objective response until the time of relapse or death within 60 days of the last administration of study drug, whichever occurs first (up to approximately 6.75 years)
Progression-Free Survival (PFS) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0)	From the first study treatment (Cy1 D1, 1 Cy = 14 days) to first occurrence of progression or death within 60 days of the last administration of study drug, whichever occurs first (up to approximately 6.75 years)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Andrea Pirzkall, M.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2010
• Primary Completion (Actual): December 3, 2013
• Study Completion (Actual): April 23, 2018

Study Registration Dates

• First Submitted: September 20, 2010
• First Submitted That Met QC Criteria: September 21, 2010
• First Posted (Estimate): September 22, 2010

Study Record Updates

• Last Update Posted (Actual): May 1, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial
• Other Study ID Numbers: DAF4873g; GO00765 (Other Identifier: Genentech, Inc.); 2010-022217-26 (EudraCT Number)