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

NCT ID: NCT01986166

Last Updated: 2016-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2016-01-31

Brief Summary

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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

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Conditions

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Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cobimetinib

Intervention Type DRUG

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.

MEHD7945A

Intervention Type DRUG

MEHD7945A will be administered as IV infusion at a dose of 1100 mg q2w until disease progression or unacceptable toxicity.

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.

Group Type EXPERIMENTAL

Cobimetinib

Intervention Type DRUG

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.

MEHD7945A

Intervention Type DRUG

MEHD7945A will be administered as IV infusion at a dose of 1100 mg q2w until disease progression or unacceptable toxicity.

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.

Group Type EXPERIMENTAL

Cobimetinib

Intervention Type DRUG

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.

MEHD7945A

Intervention Type DRUG

MEHD7945A will be administered as IV infusion at a dose of 1100 mg q2w until disease progression or unacceptable toxicity.

Interventions

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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.

Intervention Type DRUG

MEHD7945A

MEHD7945A will be administered as IV infusion at a dose of 1100 mg q2w until disease progression or unacceptable toxicity.

Intervention Type DRUG

Other Intervention Names

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GDC-0973 Duligotuzumab

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

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San Francisco, California, United States

Site Status

Denver, Colorado, United States

Site Status

New Haven, Connecticut, United States

Site Status

Detroit, Michigan, United States

Site Status

Nashville, Tennessee, United States

Site Status

Dallas, Texas, United States

Site Status

Barcelona, Barcelona, Spain

Site Status

Madrid, Madrid, Spain

Site Status

Valencia, Valencia, Spain

Site Status

Countries

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United States Spain

References

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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.

Reference Type DERIVED
PMID: 28592615 (View on PubMed)

Other Identifiers

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2013-001910-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO29030

Identifier Type: -

Identifier Source: org_study_id

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