MelanomaPhase 1NCT02027961
Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone
A Phase 1 study testing Durvalumab, Dabrafenib and Trametinib in people with Melanoma, run by MedImmune LLC at 11 sites in 4 countries.
Trial summary
The purpose of this study is to determine the maximum tolerated dose and characterize the safety profile of durvalumab (MEDI4736) in combination with dabrafenib and trametinib or with trametinib alone in participants with metastatic or unresectable melanoma with BRAF-mutation positive or wild-type (WT) BRAF… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Durvalumab, Dabrafenib and Trametinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 20 Dec 2013to 24 Apr 2018
- 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
- Adults >= 18 years old
- 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
Who cannot join
- Prior treatment with a BRAF inhibitor or MEK inhibitor
- 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
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States7 sites
Research Site
Boston, Massachusetts, 02114
Research Site
Chicago, Illinois, 60611
Research Site
Los Angeles, California, 90095
Research Site
Miami Beach, Florida, 33140
Research Site
San Francisco, California, 94115
Research Site
Scottsdale, Arizona, 85258
Research Site
St Louis, Missouri, 63110
Canada2 sites
Research Site
Montreal, Quebec, H3A 1A1
Research Site
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase 1 Open-label Study of Safety and Tolerability of MEDI4736 in Subjects With Metastatic or Unresectable Melanoma in Combination With Dabrafenib and Trametinib or With Trametinib Alone
The purpose of this study is to determine the maximum tolerated dose and characterize the safety profile of durvalumab (MEDI4736) in combination with dabrafenib and trametinib or with trametinib alone in participants with metastatic or unresectable melanoma with BRAF-mutation positive or wild-type (WT) BRAF, respectively.
Read the detailed description
This is a multicenter, open-label study with a dose escalation phase followed by an expansion phase of durvalumab administered in combination with dabrafenib and trametinib or with trametinib alone in participants with BRAF V600 mutation-positive and WT unresectable or metastatic melanoma, respectively.
- Conditions
- Melanoma
- Being tested
- Durvalumab, Dabrafenib, Trametinib
- Keywords
- Metastatic or Unresectable Melanoma, durvalumab (MEDI4736), dafrafenib, trametinib, BRAF-mutation positive, wild-type BRAF, PD-L1, PD-1
- Medical subject headings
- Melanoma, Neoplasm Metastasis, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabBiological
Intravenous dose of 3 or 10 mg/kg durvalumab.
DabrafenibDrug
Oral dose of 150 mg dabrafenib capsule.
TrametinibDrug
Oral dose of 2 mg trametinib tablet.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A1: Durvalumab (3 mg/kg) + Dabrafenib +Trametinib | Experimental | 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. Receives: Biological: Durvalumab; Drug: Dabrafenib; Drug: Trametinib |
| Cohort A2: Durvalumab (10 mg/kg) + Dabrafenib +Trametinib | Experimental | 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. Receives: Biological: Durvalumab; Drug: Dabrafenib; Drug: Trametinib |
| Cohort B: Durvalumab (10 mg/kg) +Trametinib (Concurrent) | Experimental | 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. Receives: Biological: Durvalumab; Drug: Trametinib |
| Cohort C: Durvalumab (10 mg/kg) +Trametinib (Sequential) | Experimental | 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. Receives: Biological: Durvalumab; Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs)
Dose limiting toxicities are defined as any Grade 3 or higher treatment-related (related to any study drug) toxicity that occurs during the DLT evaluation period. Number of participants with DLTs are reported.
Measured: From first dose of study drug (Day 1) until the planned 3rd dose of durvalumab (Day 29)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Measured: From first dose of study drug (Day 1) up to 90 days after the last dose (up to 4.5 years)
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs
Number of participants with abnormal vital signs and physical examinations reported as TEAEs are reported.
Measured: From first dose of study drug (Day 1) up to 90 days after the last dose (up to 4.5 years)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.
Measured: From first dose of study drug (Day 1) up to 90 days after the last dose (up to 4.5 years)
Number of Participants With Abnormal Electrocardiograms (ECGs) and Echocardiograms (ECHOs) Reported as TEAEs
Number of participants with abnormal electrocardiograms (ECGs) and echocardiograms (ECHOs) reported as TEAEs are reported.
Measured: From first dose of study drug (Day 1) up to 90 days after the last dose (up to 4.5 years)
Secondary outcomes (9)
Percentage of Participants With Objective Response (OR)
Objective Response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). A confirmed CR is defined as two CRs that were separated by at least 28 days. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days. A CR is defined as disappearance of all target and non-target lesions, normalization of tumor marker level and any pathological lymph nodes selected as target lesions must have a reduction in short axis to less than 10 mm. A PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Duration of Response (DOR)
Duration of response: Duration from first documentation of OR to first documented PD or death due to any cause, whichever occurs first. CR: disappearance of all target and non-target lesions, normalization of tumor marker level and any pathological lymph nodes selected as target lesions must have a reduction in short axis to less than 10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of >= 5 mm, taking as reference smallest sum of diameters since treatment started including baseline sum of diameters.
Measured: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Progression-free Survival (PFS)
Progression-free Survival is defined as duration from the start of treatment with study drug until the first documented PD or death, whichever comes first. PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of >= 5 mm, taking as reference smallest sum of diameters since treatment started including baseline sum of diameters. For participants who are alive and progression-free at the time of data cut-off for analysis, PFS was to be censored at the last tumor assessment date.
Measured: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Overall Survival
Overall survival (OS) is measured from the start of treatment until death. For participants who are alive at the end of study or lost to follow-up, OS was censored on the last date when participants are known to be alive.
Measured: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Percentage of Participants With Disease Control
Disease control is defined as confirmed CR or PR, or stable disease (SD) that was maintained for >= 12 weeks based on RECIST v1.1. A confirmed CR is defined as two CRs that were separated by at least 28 days. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days. CR: disappearance of all target and non-target lesions, normalization of tumor marker level and any pathological lymph nodes selected as target lesions must have a reduction in short axis to less than 10 mm. A PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. A SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study.
Measured: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Maximum Observed Plasma Concentration after First Dose (Cmax, 1st) of Durvalumab
Maximum observed plasma concentration of durvalumab after first dose is reported.
Measured: Cohorts A and B: End of infusion on Day 1; Cohort C: End of infusion on Day 29
Maximum Observed Plasma Concentration at Steady State (Cmax, ss) of Durvalumab
Maximum observed plasma concentration of durvalumab at steady state is reported.
Measured: Cohorts A and B: end of infusion on Day 141; Cohort C: end of infusion on Day 169
Trough Concentration at Steady State (Ctrough) of Durvalumab
Trough concentration of durvalumab pre-dose at steady state is reported.
Measured: Cohorts A and B: Pre-dose on Day 141; Cohort C: Pre-dose on Day 169
Number of Participants With Postive Anti-Drug Antibodies (ADA) Titer to Durvalumab
The number of participants with positive serum antibodies to durvalumab post dosing are reported.
Measured: Cohorts A and B: Days 1 and 29; Cohort C: Days 29 and 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2014 (estimated)
- Study start20 Dec 2013
- Primary completion24 Apr 2018
- Study completion24 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- 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
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MedImmune LLC, Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02027961
- Sponsor's protocol ID
- CD-ON-MEDI4736-1161
- Status last verified
- May 2019
- First submitted
- 20 Nov 2013
- Last updated
- 17 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 33288749
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-label Study of Safety and Tolerability of MEDI4736 in Subjects With Metastatic or Unresectable Melanoma in Combination With Dabrafenib and Trametinib or With Trametinib Alone
- ClinicalTrials.gov ID
- NCT02027961
- Acronym / sponsor ID
- CD-ON-MEDI4736-1161
- Conditions
- Melanoma
- Keywords
- Metastatic or Unresectable Melanoma, durvalumab (MEDI4736), dafrafenib, trametinib, BRAF-mutation positive, wild-type BRAF, PD-L1, PD-1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 20 Dec 2013 (actual)
- Primary completion
- 24 Apr 2018 (actual)
- Study completion
- 24 Apr 2018 (actual)
- First posted
- 6 Jan 2014 (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.
The purpose of this study is to determine the maximum tolerated dose and characterize the safety profile of durvalumab (MEDI4736) in combination with dabrafenib and trametinib or with trametinib alone in participants with metastatic or unresectable melanoma with BRAF-mutation positive or wild-type (WT) BRAF, respectively.
Detailed description
This is a multicenter, open-label study with a dose escalation phase followed by an expansion phase of durvalumab administered in combination with dabrafenib and trametinib or with trametinib alone in participants with BRAF V600 mutation-positive and WT unresectable or metastatic melanoma, respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort A1: Durvalumab (3 mg/kg) + Dabrafenib +Trametinib | Experimental | Biological: Durvalumab, Drug: Dabrafenib, Drug: TrametinibParticipants 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. |
| Cohort A2: Durvalumab (10 mg/kg) + Dabrafenib +Trametinib | Experimental | Biological: Durvalumab, Drug: Dabrafenib, Drug: TrametinibParticipants 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. |
| Cohort B: Durvalumab (10 mg/kg) +Trametinib (Concurrent) | Experimental | Biological: Durvalumab, Drug: TrametinibParticipants 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. |
| Cohort C: Durvalumab (10 mg/kg) +Trametinib (Sequential) | Experimental | Biological: Durvalumab, Drug: TrametinibParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults >= 18 years old
- 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
Key exclusion criteria (7 listed)
- Prior treatment with a BRAF inhibitor or MEK inhibitor
- 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
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 |
|---|---|---|
| DurvalumabIntravenous dose of 3 or 10 mg/kg durvalumab. | Biological | Cohort A1: Durvalumab (3 mg/kg) + Dabrafenib +Trametinib, Cohort A2: Durvalumab (10 mg/kg) + Dabrafenib +Trametinib, Cohort B: Durvalumab (10 mg/kg) +Trametinib (Concurrent), Cohort C: Durvalumab (10 mg/kg) +Trametinib (Sequential) |
| DabrafenibOral dose of 150 mg dabrafenib capsule. | Drug | Cohort A1: Durvalumab (3 mg/kg) + Dabrafenib +Trametinib, Cohort A2: Durvalumab (10 mg/kg) + Dabrafenib +Trametinib |
| TrametinibOral dose of 2 mg trametinib tablet. | Drug | Cohort A1: Durvalumab (3 mg/kg) + Dabrafenib +Trametinib, Cohort A2: Durvalumab (10 mg/kg) + Dabrafenib +Trametinib, Cohort B: Durvalumab (10 mg/kg) +Trametinib (Concurrent), Cohort C: Durvalumab (10 mg/kg) +Trametinib (Sequential) |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: From first dose of study drug (Day 1) until the planned 3rd dose of durvalumab (Day 29)
Dose limiting toxicities are defined as any Grade 3 or higher treatment-related (related to any study drug) toxicity that occurs during the DLT evaluation period. Number of participants with DLTs are reported.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of study drug (Day 1) up to 90 days after the last dose (up to 4.5 years)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs
Time frame: From first dose of study drug (Day 1) up to 90 days after the last dose (up to 4.5 years)
Number of participants with abnormal vital signs and physical examinations reported as TEAEs are reported.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Time frame: From first dose of study drug (Day 1) up to 90 days after the last dose (up to 4.5 years)
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.
Number of Participants With Abnormal Electrocardiograms (ECGs) and Echocardiograms (ECHOs) Reported as TEAEs
Time frame: From first dose of study drug (Day 1) up to 90 days after the last dose (up to 4.5 years)
Number of participants with abnormal electrocardiograms (ECGs) and echocardiograms (ECHOs) reported as TEAEs are reported.
9 secondary outcomes
Percentage of Participants With Objective Response (OR)
Time frame: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Duration of Response (DOR)
Time frame: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Progression-free Survival (PFS)
Time frame: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Overall Survival
Time frame: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Percentage of Participants With Disease Control
Time frame: From the first dose of study drug until last participant completes 12 months of treatment (assessed up to 4.5 years)
Maximum Observed Plasma Concentration after First Dose (Cmax, 1st) of Durvalumab
Time frame: Cohorts A and B: End of infusion on Day 1; Cohort C: End of infusion on Day 29
Maximum Observed Plasma Concentration at Steady State (Cmax, ss) of Durvalumab
Time frame: Cohorts A and B: end of infusion on Day 141; Cohort C: end of infusion on Day 169
Trough Concentration at Steady State (Ctrough) of Durvalumab
Time frame: Cohorts A and B: Pre-dose on Day 141; Cohort C: Pre-dose on Day 169
Number of Participants With Postive Anti-Drug Antibodies (ADA) Titer to Durvalumab
Time frame: Cohorts A and B: Days 1 and 29; Cohort C: Days 29 and 57
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 17 May 2019.
- BackgroundGordon 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).
- Results publicationRibas 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).
- Derived from this study: PubMed 33288749Ribas 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.
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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.
MedImmune LLC study director
MedImmune LLC
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Durvalumab, Dabrafenib and Trametinib in people with Melanoma, run by MedImmune LLC at 11 sites in 4 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 6 inclusion and 7 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 17 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada, France, Italy. 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?
Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: From first dose of study drug (Day 1) until the planned 3rd dose of durvalumab (Day 29)). The study lists 5 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 NCT02027961, which also lists 3 linked publications.
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 17 May 2019.