A Phase 1b Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in Combination With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01988896
First received: November 14, 2013
Last updated: March 23, 2015
Last verified: March 2015
  Purpose

A Phase Ib, open-label, multicenter study designed to assess the safety, tolerability, and pharmacokinetics of coadministration of MPDL3280A and of cobimetinib in patients with metastatic or locally advanced cancer for which no standard of care exists.


Condition Intervention Phase
Neoplasms
Drug: Cobimetinib
Drug: MPDL3280A
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Study of the Safety and Pharmacology of MPDL3280A Administered With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Safety: Incidence of adverse events (AE) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Safety: Incidence of dose-limiting toxicities (DLT) [ Time Frame: 28 days following start of combination treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Maximum concentration (Cmax) of MPDL3280A [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Plasma Cmax of Cobimetinib [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]

Enrollment: 91
Study Start Date: January 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose-expansion: cobimetinib + MPDL3280A Drug: Cobimetinib
Fixed dose of cobimetinib adminstered orally
Drug: MPDL3280A
Fixed dose administered by IV
Experimental: Dose-finding: cobimetinib + MPDL3280A Drug: Cobimetinib
Escalating doses of cobimetinib administered orally
Drug: MPDL3280A
Fixed dose administered by IV

  Eligibility

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

Inclusion Criteria:

  • Age >/= 18 years.
  • Solid tumor that is metastatic, locally advanced or recurrent.
  • ECOG performance status of 0 or 1.
  • Life expectancy >/= 12 weeks.
  • Measurable disease, as defined by RECIST v1.1.
  • Adequate blood and organ function.
  • Use of highly effective contraception.
  • Histological tumor tissue specimen.
  • Patients enrolling in the expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer:
  • KRAS-mutant metatastic colorectal cancer (mCRC)
  • Non-small cell lung cancer (NSCLC)
  • Melanoma

Exclusion Criteria:

  • Pregnant and lactating women.
  • History of autoimmune disease.
  • Patients with prior stem cell or organ transplant.
  • History of idiopathic pulmonary fibrosis.
  • History of HIV or hepatitis C infection; history of hepatitis B is allowed if infection has resolved (absence of HBsAG).
  • Severe infections within 4 weeks prior to study start; signs or symptoms of infection within 2 weeks prior to study start.
  • Oral or IV antibiotic therapy within 2 weeks prior to study start.
  • Significant cardiovascular disease.
  • Administration of a live, attenuated vaccine within 4 weeks before study start or until the end of the study.

Cancer-Specific Exclusions

  • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to study start.
  • Active or untreated central nervous system (CNS) tumors.
  • Leptomeningeal disease.
  • Excess, uncontrolled calcium levels.
  • History of prior significant toxicity from another MEK pathway inhibitor requiring discontinuation of treatment.
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies.
  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: NCT01988896

  Hide Study Locations
Locations
United States, California
Stanford, California, United States, 94305
United States, Colorado
Denver, Colorado, United States, 80220
United States, Connecticut
New Haven, Connecticut, United States, 06510
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02215
United States, New York
New York, New York, United States, 10065
United States, North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Arlington, Texas, United States, 76012
Tyler, Texas, United States, 75702
United States, Washington
Seattle, Washington, United States, 98195
Vancouver, Washington, United States, 98684
Australia, Victoria
Box Hill, Victoria, Australia, 3128
Parkville, Victoria, Australia, 3050
Canada, Ontario
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
Montréall, Quebec, Canada, H2L 4M1
Germany
Dresden, Germany, 01307
Freiburg, Germany, 79106
Korea, Republic of
Seoul, Korea, Republic of, 110-774
Seoul, Korea, Republic of, 138-736
Singapore
Singapore, Singapore, 188770
Singapore, Singapore, 119074
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: NCT01988896     History of Changes
Other Study ID Numbers: GP28363
Study First Received: November 14, 2013
Last Updated: March 23, 2015
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on March 31, 2015