Clinical Trial: NCT01986166 - My Cancer Genome

NCT01986166

Description:

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).

Related Conditions:

Malignant Solid Tumor

Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT01986166

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: GO29030
SECONDARY ID: 2013-001910-14
NCT ID: NCT01986166

Conditions

Neoplasms

Interventions

Drug	Synonyms	Arms
Cobimetinib	GDC-0973	MEHD7945A + Cobimetinib - Stage 1
MEHD7945A	Duligotuzumab	MEHD7945A + Cobimetinib - Stage 1

Purpose

Trial Arms

Name	Type	Description	Interventions
MEHD7945A + Cobimetinib - Stage 1	Experimental	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.	Cobimetinib MEHD7945A
MEHD7945A + Cobimetinib - Stage 2 (CRC)	Experimental	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.	Cobimetinib MEHD7945A
MEHD7945A + Cobimetinib - Stage 2 (NSCLC)	Experimental	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.	Cobimetinib MEHD7945A

Eligibility 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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Percentage of patients with adverse events
Time Frame:	up to approximately 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Completed
Lead Sponsor:	Genentech, Inc.

Last Updated

July 18, 2016

Clinical Trials /

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