Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone
NCT ID: NCT02027961
Last Updated: 2019-05-17
Study Results
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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COMPLETED
PHASE1
68 participants
INTERVENTIONAL
2013-12-20
2018-04-24
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort A1: Durvalumab (3 mg/kg) + Dabrafenib +Trametinib
Participants will receive intravenous (IV) dose of 3 milligrams per kilogram (mg/kg) durvalumab every 2 weeks (Q2W) from Day 1 up to 12 months along with oral 150 mg dabrafenib capsule twice daily (BID) and oral 2 mg trametinib tablet once daily (QD) until confirmed disease progression (PD), initiation of alternate cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment. Post-durvalumab treatment period, participants who developed PD and meet the criteria for re-administration, will receive durvalumab 3 mg/kg up to an additional 12 months and continued the treatment of dabrafenib and trametinib.
Durvalumab
Intravenous dose of 3 or 10 mg/kg durvalumab.
Dabrafenib
Oral dose of 150 mg dabrafenib capsule.
Trametinib
Oral dose of 2 mg trametinib tablet.
Cohort A2: Durvalumab (10 mg/kg) + Dabrafenib +Trametinib
Participants will receive IV dose of 10 mg/kg durvalumab Q2W from Day 1 up to 12 months along with oral doses of dabrafenib 150 mg capsule BID and trametinib 2 mg tablet QD until confirmed PD, initiation of alternate cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment. Post-durvalumab treatment period, participants who developed PD and meet the criteria for re-administration, will receive durvalumab 10 mg/kg up to an additional 12 months and continued the treatment of dabrafenib and trametinib.
Durvalumab
Intravenous dose of 3 or 10 mg/kg durvalumab.
Dabrafenib
Oral dose of 150 mg dabrafenib capsule.
Trametinib
Oral dose of 2 mg trametinib tablet.
Cohort B: Durvalumab (10 mg/kg) +Trametinib (Concurrent)
Participants will receive concurrent doses of IV 10 mg/kg durvalumab Q2W from Day 1 up to 12 months along with oral dose of trametinib 2 mg tablet QD until confirmed PD, initiation of alternate cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment. Post-durvalumab treatment period, participants who developed PD and meet the criteria for re-administration, will receive durvalumab 10 mg/kg up to an additional 12 months and continued the treatment of trametinib.
Durvalumab
Intravenous dose of 3 or 10 mg/kg durvalumab.
Trametinib
Oral dose of 2 mg trametinib tablet.
Cohort C: Durvalumab (10 mg/kg) +Trametinib (Sequential)
Participants will receive sequential doses of oral trametinib tablet 2 mg QD from Day 1 to Day 42 and IV durvalumab 10 mg/kg Q2W starting from Day 29 (Week 5) up to 12 months. Post-durvalumab treatment period, participants who developed PD and meet the criteria for re-administration, will receive durvalumab 10 mg/kg up to an additional 12 months.
Durvalumab
Intravenous dose of 3 or 10 mg/kg durvalumab.
Trametinib
Oral dose of 2 mg trametinib tablet.
Interventions
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Durvalumab
Intravenous dose of 3 or 10 mg/kg durvalumab.
Dabrafenib
Oral dose of 150 mg dabrafenib capsule.
Trametinib
Oral dose of 2 mg trametinib tablet.
Eligibility Criteria
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Inclusion Criteria
* Histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable) or Stage IV (metastatic) and determined to be BRAF V600E or V600K mutation-positive (cohort A) or mutation-negative (cohorts B and C)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Measurable disease by radiographic or physical examination
* Adequate organ and marrow function
* Willingness to provide consent for biopsies positive or BRAF WT measurable disease and adequate organ and marrow function
Exclusion Criteria
* Any prior Grade \>= 3 immune-related adverse event while receiving immunotherapy
* Active or prior documented autoimmune disease within the past 2 years
* History of or current risk for retinal vein occlusion (RVO) or central serous retinopathy (CSR)
* History of or current cardiovascular risk including myocardial infarction, \>= Class II congestive heart failure, uncontrolled arrhythmias, or refractory hypertension
* Active, untreated central nervous system (CNS) metastases
* Women who are pregnant or lactating
18 Years
ALL
No
Sponsors
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MedImmune LLC
INDUSTRY
Responsible Party
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Principal Investigators
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MedImmune LLC
Role: STUDY_DIRECTOR
MedImmune LLC
Locations
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Research Site
Scottsdale, Arizona, United States
Research Site
Los Angeles, California, United States
Research Site
San Francisco, California, United States
Research Site
Miami Beach, Florida, United States
Research Site
Chicago, Illinois, United States
Research Site
Boston, Massachusetts, United States
Research Site
St Louis, Missouri, United States
Research Site
Toronto, Ontario, Canada
Research Site
Montreal, Quebec, Canada
Research Site
Villejuif, , France
Research Site
Napoli, , Italy
Countries
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References
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Gordon MS, Lutzky J, Lawrence D, Butler M, Ascierto PA, Hug B, et al. Phase 1 study evaluating safety and tolerability of MEDI4736, an anti-programmed cell death ligand-1 (PD-L1) antibody, in combination with dabrafenib and trametinib or trametinib alone in patients with unresectable or metastatic melanoma. Ann Oncol 2014; 25(suppl_4): iv374-iv393 (abstract 8004).
Ribas A, Butler M, Lutzky J, Lawrence DP, Robert C, Miller W, et al. Phase 1 study combining anti-PD-L1 (MEDI4736) and BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in advanced melanoma. J Clin Oncol 2015; 33 (15_suppl): (abstract 3003).
Ribas A, Algazi A, Ascierto PA, Butler MO, Chandra S, Gordon M, Hernandez-Aya L, Lawrence D, Lutzky J, Miller WH Jr, Campbell KM, Delafont B, Marshall S, Mueller N, Robert C. PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma. Nat Commun. 2020 Dec 7;11(1):6262. doi: 10.1038/s41467-020-19810-w.
Other Identifiers
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CD-ON-MEDI4736-1161
Identifier Type: -
Identifier Source: org_study_id
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