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

Neoplasms Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT01986166
• Other study ID #: GO29030
• Secondary ID: 2013-001910-14
• Status: Completed
• Phase: Phase 1
• First received: November 1, 2013
• Last updated: July 14, 2016
• Start date: November 2013
• Est. completion date: January 2016

Study information

• Verified date: July 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with adverse events		up to approximately 2 years	No
Primary	Percentage of patients with anti-MEHD7945A antibodies		up to approximately 2 years	Yes
Primary	Percentage of patients with dose-limiting toxicities (DLTs)		28 days	Yes
Secondary	Percentage of patients with fluorodeoxyglucose positron emission tomography (PET) response, defined as a >=20% decrease in fluorodeoxyglucose uptake by PET		Baseline, Day 15 of Cycle 1 (cycle length=28 days)	No
Secondary	MEHD7945A maximum serum concentrations (Cmax)		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)	No
Secondary	MEHD7945A minimum serum concentrations (Cmin)		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)	No
Secondary	Cobimetinib area under the concentration-time curve (AUC)		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)	No
Secondary	Cobimetinib maximum plasma concentrations (Cmax)		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)	No
Secondary	Time to maximum cobimetinib plasma concentration (tmax)		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)	No
Secondary	Percentage of patients with objective response		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)	No
Secondary	Duration of objective response		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)	No
Secondary	Progression-free survival		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)	No