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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01986166
Recruitment Status : Completed
First Posted : November 18, 2013
Last Update Posted : July 18, 2016
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE November 1, 2013
First Posted Date  ICMJE November 18, 2013
Last Update Posted Date July 18, 2016
Study Start Date  ICMJE November 2013
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2016)
  • Percentage of patients with adverse events [ Time Frame: up to approximately 2 years ]
  • Percentage of patients with anti-MEHD7945A antibodies [ Time Frame: up to approximately 2 years ]
  • Percentage of patients with dose-limiting toxicities (DLTs) [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 11, 2013)
  • Safety: Incidence and nature of dose-limiting toxicities (DLTs) [ Time Frame: 28 days ]
  • Safety: Incidence, nature and severity of adverse events [ Time Frame: approximately 2 years ]
  • Safety: Incidence of anti-MEHD7945A antibodies [ Time Frame: approximately 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2016)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2013)
  • Pharmacokinetics: MEHD7945A maximum serum concentrations (Cmax) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ]
  • Pharmacokinetics: MEHD7945A minimum serum concentrations (Cmin) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ]
  • Pharmacokinetics: Cobimetinib area under the concentration-time curve (AUC) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ]
  • Pharmacokinetics: Cobimetinib maximum plasma concentrations (Cmax) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ]
  • Pharmacokinetics: Time to maximum cobimetinib plasma concentration (tmax) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ]
  • Objective response, defined as a complete or partial response >/= 4 weeks after the initial documentation [ Time Frame: approximately 2 years ]
  • Duration of objective response [ Time Frame: approximately 2 years ]
  • Progression-free survival [ Time Frame: approximately 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of MEHD7945A and Cobimetinib in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS
Official Title  ICMJE 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
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Cobimetinib
    • Drug: MEHD7945A
  • 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.
    Interventions:
    • Drug: Cobimetinib
    • Drug: MEHD7945A
  • 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.
    Interventions:
    • Drug: Cobimetinib
    • Drug: MEHD7945A
Publications * Lieu CH, Hidalgo M, Berlin JD, Ko AH, Cervantes A, LoRusso P, Gerber DE, Eder JP, Eckhardt SG, Kapp AV, Tsuhako A, McCall B, Pirzkall A, Uyei A, Tabernero J. A Phase Ib Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Cobimetinib and Duligotuzumab in Patients with Previously Treated Locally Advanced or Metastatic Cancers with Mutant KRAS. Oncologist. 2017 Sep;22(9):1024-e89. doi: 10.1634/theoncologist.2017-0175. Epub 2017 Jun 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 14, 2016)
23
Original Estimated Enrollment  ICMJE
 (submitted: November 11, 2013)
50
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01986166
Other Study ID Numbers  ICMJE GO29030
2013-001910-14 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Genentech, Inc.
PRS Account Genentech, Inc.
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP