NeoplasmsPhase 1NCT01986166
A Study of MEHD7945A and Cobimetinib in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS
A Phase 1 study testing Cobimetinib and MEHD7945A in people with Neoplasms, run by Genentech, Inc. at 9 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Cobimetinib and MEHD7945A
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Nov 2013to Jan 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States6 sites
Study site
Dallas, Texas, 75390-8852
Study site
Denver, Colorado, 80262
Study site
Detroit, Michigan, 48201
Study site
Nashville, Tennessee, 37212
Study site
New Haven, Connecticut, 06520
Study site
San Francisco, California, 94115
Spain3 sites
Study site
Barcelona, Barcelona, 08035
Study site
Madrid, Madrid, 28050
Study site
Valencia, Valencia, 46010
About this study
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
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).
- Conditions
- Neoplasms
- Being tested
- Cobimetinib, MEHD7945A
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CobimetinibDrug
Also called GDC-0973
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.
MEHD7945ADrug
Also called Duligotuzumab
MEHD7945A will be administered as IV infusion at a dose of 1100 mg q2w until disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cobimetinib; Drug: 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. Receives: Drug: Cobimetinib; Drug: 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. Receives: Drug: Cobimetinib; Drug: MEHD7945A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with adverse events
Measured: up to approximately 2 years
Percentage of patients with anti-MEHD7945A antibodies
Measured: up to approximately 2 years
Percentage of patients with dose-limiting toxicities (DLTs)
Measured: 28 days
Secondary outcomes (9)
Percentage of patients with fluorodeoxyglucose positron emission tomography (PET) response, defined as a >=20% decrease in fluorodeoxyglucose uptake by PET
Measured: Baseline, Day 15 of Cycle 1 (cycle length=28 days)
MEHD7945A maximum serum concentrations (Cmax)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2013 (estimated)
- Study startNov 2013
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01986166
- Sponsor's protocol ID
- GO29030
- Other IDs
- 2013-001910-14
- Status last verified
- Jul 2016
- First submitted
- 1 Nov 2013
- Last updated
- 18 Jul 2016
- Results posted
- No
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.
PubMed 28592615
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01986166
- Acronym / sponsor ID
- GO29030
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 18 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MEHD7945A + Cobimetinib - Stage 1 | Experimental | Drug: Cobimetinib, Drug: MEHD7945APatients 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. |
| MEHD7945A + Cobimetinib - Stage 2 (CRC) | Experimental | Drug: Cobimetinib, Drug: MEHD7945ACRC 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. |
| MEHD7945A + Cobimetinib - Stage 2 (NSCLC) | Experimental | Drug: Cobimetinib, Drug: MEHD7945ANSCLC 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CobimetinibAlso: GDC-0973In 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. | Drug | MEHD7945A + Cobimetinib - Stage 1, MEHD7945A + Cobimetinib - Stage 2 (CRC), MEHD7945A + Cobimetinib - Stage 2 (NSCLC) |
| MEHD7945AAlso: DuligotuzumabMEHD7945A will be administered as IV infusion at a dose of 1100 mg q2w until disease progression or unacceptable toxicity. | Drug | MEHD7945A + Cobimetinib - Stage 1, MEHD7945A + Cobimetinib - Stage 2 (CRC), MEHD7945A + Cobimetinib - Stage 2 (NSCLC) |
Primary outcome
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
9 secondary outcomes
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2016.
- Derived from this study: PubMed 28592615Lieu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Genentech, Inc.
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cobimetinib and MEHD7945A in people with Neoplasms, run by Genentech, Inc. at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with adverse events (time frame: up to approximately 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01986166, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2016.