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A Study of MEHD7945A and Cobimetinib in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01986166
First received: November 1, 2013
Last updated: July 14, 2016
Last verified: July 2016
  Purpose
This open-label, multicenter, global Phase Ib study will evaluate the safety, tolerability and pharmacokinetics of intravenous (IV) dosing of MEHD7945A in combination with oral dosing of cobimetinib in patients with locally advanced or metastatic solid tumors that carry a Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutation and for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate. The study comprises a dose-escalation (Stage 1) and an indication-specific cohort expansion stage (Stage 2).

Condition Intervention Phase
Neoplasms
Drug: Cobimetinib
Drug: MEHD7945A
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 Ib, Open-Label, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of MEHD7945A and Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors With Mutant KRAS

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Percentage of patients with adverse events [ Time Frame: up to approximately 2 years ] [ Designated as safety issue: No ]
  • Percentage of patients with anti-MEHD7945A antibodies [ Time Frame: up to approximately 2 years ] [ Designated as safety issue: Yes ]
  • Percentage of patients with dose-limiting toxicities (DLTs) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of patients with fluorodeoxyglucose positron emission tomography (PET) response, defined as a >=20% decrease in fluorodeoxyglucose uptake by PET [ Time Frame: Baseline, Day 15 of Cycle 1 (cycle length=28 days) ] [ Designated as safety issue: No ]
  • MEHD7945A maximum serum concentrations (Cmax) [ Time Frame: Pre-dose (0 hour) on Days 1, 15 and 0.5 hour post-infusion (infusion duration=1.5 hour) on Days 1, 15 of Cycles 1, 2 and pre-dose (0 hour) and 0.5 hour post-infusion (infusion duration=1 hour) on Day 15 of Cycle 4 (up to 14 weeks) (cycle length=28 days) ] [ Designated as safety issue: No ]
  • MEHD7945A minimum serum concentrations (Cmin) [ Time Frame: Pre-dose (0 hour) on Days 1, 15 of Cycles 1, 2 and pre-dose (0 hour) on Day 15 of Cycle 4 (up to 14 weeks) (cycle length=28 days) ] [ Designated as safety issue: No ]
  • Cobimetinib area under the concentration-time curve (AUC) [ Time Frame: Pre-dose (0 hour), 1, 2, 4 hour post-infusion (infusion duration=1.5 hour) on Cycle 1 Days 1 & 15 and Cycle 4 Day 15, 6 & 24 hours post-infusion on Cycle 1 Day 15, 6 hour post-infusion on Cycle 4 Day 15 (up to 14 weeks) (cycle length=28 days) ] [ Designated as safety issue: No ]
  • Cobimetinib maximum plasma concentrations (Cmax) [ Time Frame: Pre-dose (0 hour), 1, 2, 4 hour post-infusion (infusion duration=1.5 hour) on Cycle 1 Days 1 & 15 and Cycle 4 Day 15, 6 & 24 hours post-infusion on Cycle 1 Day 15, 6 hour post-infusion on Cycle 4 Day 15 (up to 14 weeks) (cycle length=28 days) ] [ Designated as safety issue: No ]
  • Time to maximum cobimetinib plasma concentration (tmax) [ Time Frame: Pre-dose (0 hour), 1, 2, 4 hour post-infusion (infusion duration=1.5 hour) on Cycle 1 Days 1 & 15 and Cycle 4 Day 15, 6 & 24 hours post-infusion on Cycle 1 Day 15, 6 hour post-infusion on Cycle 4 Day 15 (up to 14 weeks) (cycle length=28 days) ] [ Designated as safety issue: No ]
  • Percentage of patients with objective response [ Time Frame: Baseline, Days 22 of Cycle 2 and Day 25 of Cycle 4 and then every 8 weeks throughout the duration of the study (up to approximately 2 years) (cycle length=28 days) ] [ Designated as safety issue: No ]
  • Duration of objective response [ Time Frame: Baseline, Day 22 of Cycle 2 and Day 25 of Cycle 4 and then every 8 weeks throughout the duration of the study (up to approximately 2 years) (cycle length=28 days) ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Baseline, Day 22 of Cycle 2 and Day 25 of Cycle 4 and then every 8 weeks throughout the duration of the study (up to approximately 2 years) (cycle length=28 days) ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: November 2013
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEHD7945A + Cobimetinib - Stage 1
Patients will receive MEHD7945A 1100 milligrams (mg) intravenous (IV) infusion every 2 weeks (q2w) in combination with cobimetinib. Cobimetinib will be administered at a starting dose of 80 mg oral tablet q2w. Cobimetinib doses will be escalated to establish maximum tolerated dose (MTD) of MEHD7945A+cobimetinib combination for Stage 2.
Drug: Cobimetinib
In Stage 1, cobimetinib will be administered at a starting dose of 80 mg q2w. The doses will be escalated to identify MTD. In Stage 2, participants will receive cobimetinib at the established MTD.
Other Name: GDC-0973
Drug: MEHD7945A
MEHD7945A will be administered as IV infusion at a dose of 1100 mg q2w until disease progression or unacceptable toxicity.
Other Name: Duligotuzumab
Experimental: MEHD7945A + Cobimetinib - Stage 2 (CRC)
CRC patients will receive MEHD7945A in combination with cobimetinib until disease progression or unacceptable toxicity. The doses and schedule of the combination treatment will be according to the MTD established in Stage 1.
Drug: Cobimetinib
In Stage 1, cobimetinib will be administered at a starting dose of 80 mg q2w. The doses will be escalated to identify MTD. In Stage 2, participants will receive cobimetinib at the established MTD.
Other Name: GDC-0973
Drug: MEHD7945A
MEHD7945A will be administered as IV infusion at a dose of 1100 mg q2w until disease progression or unacceptable toxicity.
Other Name: Duligotuzumab
Experimental: MEHD7945A + Cobimetinib - Stage 2 (NSCLC)
NSCLC patients will receive MEHD7945A in combination with cobimetinib until disease progression or unacceptable toxicity. The doses and schedule of the combination treatment will be according to the MTD established in Stage 1.
Drug: Cobimetinib
In Stage 1, cobimetinib will be administered at a starting dose of 80 mg q2w. The doses will be escalated to identify MTD. In Stage 2, participants will receive cobimetinib at the established MTD.
Other Name: GDC-0973
Drug: MEHD7945A
MEHD7945A will be administered as IV infusion at a dose of 1100 mg q2w until disease progression or unacceptable toxicity.
Other Name: Duligotuzumab

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Locally advanced or metastatic solid KRAS-mutant tumors, for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Evaluable disease or disease measurable per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
  • Consent to provide archival tumor tissue for biomarker testing
  • Additionally, for patients who are considered for enrollment into the indication specific expansion cohorts in Stage 2, the current cancer must be either KRAS-mutant colorectal cancer (CRC) or KRAS-mutant non-small cell lung cancer (NSCLC)

Exclusion Criteria:

  • History of prior significant toxicity from another MEK pathway inhibitor or combination of another MEK and epidermal growth factor receptor (EGFR) inhibitor requiring discontinuation of treatment
  • Previous treatment with a combination of a MEK inhibitor with an EGFR inhibitor (applies only to the indication specific expansion cohorts in Stage 2)
  • Allergy or hypersensitivity to components of the cobimetinib formulations
  • History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy
  • History of interstitial lung disease (ILD)
  • Known severe ulcer disease
  • History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioetinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration

Patients will be excluded if they currently have either of the following conditions which have been identified as risk factors for CSCR:

  • Uncontrolled glaucoma with intraocular pressure greater than (>) 21 millimeters of mercury (mm Hg)
  • Grade greater than equal to (>=) 3 hypertriglyceridemia
  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: NCT01986166

Locations
United States, California
San Francisco, California, United States, 94115
United States, Colorado
Denver, Colorado, United States, 80262
United States, Connecticut
New Haven, Connecticut, United States, 06520
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Tennessee
Nashville, Tennessee, United States, 37212
United States, Texas
Dallas, Texas, United States, 75390-8852
Spain
Barcelona, Spain, 08035
Madrid, Spain, 28050
Valencia, Spain, 46010
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01986166     History of Changes
Other Study ID Numbers: GO29030  2013-001910-14 
Study First Received: November 1, 2013
Last Updated: July 14, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 28, 2016