Trial record 4 of 13 for:    MPDL3280A

A Phase 1b Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in Combination With Tarceva in Patients With Non-Small Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02013219
First received: December 11, 2013
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

This open-label, multicenter study will assess the safety, tolerability, and pha rmacokinetics of intravenous (IV) dosing of MPDL3280A and oral dosing of Tarceva (erlotinib) administered in combination to patients with non-small cell lung ca ncer (NSCLC). This study has two stages. In the safety evaluation stage, patie nts with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) -treatment-naive, advanced NSCLC will be given Tarceva at a starting daily dose of 150 mg for 28 consecutive days during Cycle 1 and for 21-day cycles thereafte r. The starting dose of MPDL3280A will be 1200 mg, administered every 3 weeks st arting on Day 8 of Cycle 1. If the starting regimen is not tolerated, alternativ e doses and/or schedules of Tarceva and MPDL3280A may be tested. In the expansi on stage, patients with previously untreated, EGFR mutation-positive, advanced N SCLC will be treated with a potential recommended phase 2 dose and schedule base d on the treatment established in safety evaluation stage. For both stages, con tinuation of treatment beyond Cycle 1 will be at the discretion of the treating investigator. In the absence of unacceptable toxicity or disease progression, tr eatment with MPDL3280A may be continued for a maximum of 17 cycles (or 12 months

, whichever occurs first). Tarceva may be continued until disease progression in the absence of unacceptable toxicity. Time on study is expected to be approxima tely 15 months.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: MPDL3280A
Drug: erlotinib [Tarceva[
Drug: erlotinib [Tarceva]
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Study of the Safety and Pharmacology of MPDL3280A Administered With Erlotinib in Patients With Advanced Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Incidence of dose-limiting toxicities [ Time Frame: Day 8, Cycle 1 until Day 1, Cycle 2 (21 days from start of MPDL3280A treatment) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of adverse events [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Incidence of anti-therapeutic antibodies against MPDL3280A [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Maximum serum concentration (Cmax) of MPDL3280A [ Time Frame: On Day 8 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration (Cmax) of Tarceva [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
  • Overall response, as determined by the investigator with RECIST v1.1 [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: April 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stage 1: Tarceva (Erlotinib) and MPDL3280A Drug: MPDL3280A
1200 mg intravenous (IV) infusion every 3 weeks.
Drug: erlotinib [Tarceva]
150 mg oral daily dose.
Experimental: Stage 2: Tarceva (Erlotinib) and MPDL3280A Drug: MPDL3280A
IV infusion every 3 weeks at recommended phase 2 dose.
Drug: erlotinib [Tarceva[
Daily oral dose at recommended phase 2 dose.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >/= 18 years.
  • Histologically or cytologically documented, locally advanced or metastatic non-small cell lung cancer (NSCLC).
  • Patients in Stage 1 (Safety Evaluation): No limit to the number of prior therapies (except for EGFR TKIs).
  • Patients in Stage 2 (Expansion):

Sensitizing mutation in the EGFR gene. Consent to collection of tumor tissue samples before, during, and after treatment for biopsy and PD biomarker analyses.

  • ECOG performance status of 0 or 1.
  • Life expectancy >/= 12 weeks.
  • Measurable disease, as defined by RECIST v1.1.
  • Adequate hematologic and end-organ function.
  • Use of highly effective contraception (as defined by protocol) until 6 months after the last dose of MPDL3280A; patients must not be pregnant or breastfeeding.
  • Tumor tissue specimen.

Exclusion Criteria:

  • Prior treatment with any EGFR mutant-targeting TKI.
  • Patients in Stage 2 may not have received any prior treatments for their NSCLC.
  • Any approved anticancer therapy, including chemotherapy, or hormonal therapy (except hormone-replacement therapy or oral contraceptives) within 3 weeks of first dose.
  • Treatment with any other test drug or participation in another clinical trial within 28 days of enrollment.
  • Known symptomatic or untreated CNS metastases. Patients with a history of treated asymptomatic CNS metastases may be eligible.
  • Leptomeningeal disease.
  • Uncontrolled tumor-related pain.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage at least once monthly.
  • High levels of calcium requiring bisphosphonate therapy or denosumab.
  • Malignancies other than NSCLC within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ).
  • History of severe allergic, anaphylactic, or other reactions to chimeric or humanized antibodies or fusion proteins.
  • History of autoimmune disease.
  • Patients with prior bone marrow or solid organ transplantation.
  • History of lung inflammation or disease.
  • Current or active tuberculosis, hepatitis B, or hepatitis C.
  • Patients with past or resolved hepatitis B virus (HBV) infection are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Signs or symptoms of infection within 2 weeks prior to first dosing.
  • Received therapeutic oral or IV antibiotics within 2 weeks prior to first dosing.
  • Significant cardiovascular disease.
  • Major surgical procedure other than for diagnosis within 28 days prior to first dosing or during the course of the study.
  • Administration of a live, attenuated vaccine within 4 weeks before first dosing or during the study.
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that may reasonably prevent the patient from participating.
  • Any significant ophthalmologic abnormality. The use of contact lenses is not recommended during the study.
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies.
  • Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of the drug, whichever is shorter, prior to first dosing.
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to first dosing (inhaled corticosteroids and mineralocorticoids are allowed).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02013219

Contacts
Contact: Reference Study ID Number: WP29158 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, Connecticut
Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Not yet recruiting
Orlando, Florida, United States, 32904
United States, Illinois
Not yet recruiting
Chicago, Illinois, United States, 60637
United States, Massachusetts
Not yet recruiting
Boston, Massachusetts, United States, 02114
Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Recruiting
New York, New York, United States, 10065
United States, Ohio
Not yet recruiting
Cleveland, Ohio, United States, 44106
Hong Kong
Not yet recruiting
Shatin, Hong Kong, 123456
Spain
Not yet recruiting
Madrid, Spain, 28050
Not yet recruiting
Valencia, Spain, 46010
United Kingdom
Not yet recruiting
New Castle upon Tyne, United Kingdom, NE2 4HH
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02013219     History of Changes
Other Study ID Numbers: WP29158
Study First Received: December 11, 2013
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014