MelanomaPhase 1NCT02180061
Study of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-041/KEYNOTE-041)
A Phase 1 study testing Pembrolizumab in people with Melanoma, run by Merck Sharp & Dohme LLC.
Trial summary
This study will assess the safety, tolerability, and efficacy of every-3-week dosing (Q3W) of pembrolizumab (MK-3475) in participants with advanced melanoma; participants may receive pembrolizumab for up to 2 years if deriving clinical benefit. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- No sites listed yet
- Study dates
- 15 Jul 2014to 31 Aug 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- At least one measurable lesion
- Adequate organ function
Who cannot join
- Prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent
- Is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5X half-life of the investigational compound, whichever is longer, of initial dosing on this study
- Chemotherapy, targeted small molecule therapy, radiotherapy, or biological cancer therapy (including monoclonal antibodies) within 4 weeks prior to the first dose of trial treatment, or not recovered (<= Grade 1 or baseline) from adverse events due to a previously administered agent
- Expected to require any other form of systemic or localized antineoplastic therapy while in study
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
Show all 13Show fewer
- Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study treatment
- Received a live vaccine within 4 weeks prior to the first dose of trial treatment
- Has a known hypersensitivity to the components of the study drug or another monoclonal antibody
- History or evidence of active pneumonitis
- Human immunodeficiency virus (HIV)-positive
- Has known history of active Hepatitis B or C
- Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial treatment through 120 days after the last dose of study medication
About this study
Official title: Phase Ib Study of MK-3475 in Subjects With Advanced Melanoma
This study will assess the safety, tolerability, and efficacy of every-3-week dosing (Q3W) of pembrolizumab (MK-3475) in participants with advanced melanoma; participants may receive pembrolizumab for up to 2 years if deriving clinical benefit. The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate.
Read the detailed description
Participants who discontinue pembrolizumab after achieving a complete response (CR) and subsequently develop progressive disease (PD) may be eligible to enter a Second Course Phase and receive pembrolizumab again.
The end of the study for each participant will occur with: 1) the marketing approval of pembrolizumab for melanoma, 2) the completion of safety follow up or 3) the time when a possibility of entry to second course of treatment is lost, whichever occurs last.
- Conditions
- Melanoma
- Being tested
- Pembrolizumab
- Keywords
- PD1, PD-1, PDL1, PD-L1
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called MK-3475
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Advanced Cutaneous Melanoma | Experimental | Participants with advanced cutaneous melanoma received pembrolizumab, 2 mg/kg, intravenously (IV) over 30 minutes on Day 1 of each 3-week dosing cycle (Q3W). Receives: Biological: Pembrolizumab |
| Advanced Mucosal Melanoma | Experimental | Participants with advanced mucosal melanoma received pembrolizumab, 2 mg/kg, IV over 30 minutes on Day 1 Q3W. Receives: Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Adverse Events (AEs)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
Measured: All AEs: Up to 30 days after last dose of study drug; Serious AEs: Up to 90 days after last dose of study drug (Up to 27 months)
Number of Participants Discontinuing Treatment Due to AEs
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
Measured: Up to last dose of study drug (Up to 24 months)
Overall Response Rate (ORR) Per Central Radiology Review Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
The ORR, using RECIST 1.1, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on central radiology review.
Measured: Up to 24 months
Secondary outcomes (2)
ORR Per Investigator Assessment Using RECIST 1.1
The ORR, using RECIST 1.1 criteria, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on Investigator assessment.
Measured: Up to 24 months
ORR Per Central Radiology Review Using Immune-related Response Criteria (irRC)
The ORR, using irRC, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (irCR; complete disappearance of all tumor lesions, whether measureable or not, and no new lesions) or a Partial Response (irPR; decrease in sum of the products of the 2 largest perpendicular diameters of 50% or greater) at any time during the study, based on central radiology review.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2014 (estimated)
- Study start15 Jul 2014
- Primary completion31 Aug 2017
- Study completion31 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02180061
- Sponsor's protocol ID
- 3475-041
- Other IDs
- 142637, MK-3475-041, KEYNOTE-041
- Status last verified
- Mar 2020
- First submitted
- 1 Jul 2014
- Last updated
- 31 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Yamazaki N, Takenouchi T, Fujimoto M, Ihn H, Uchi H, Inozume T, Kiyohara Y, Uhara H, Nakagawa K, Furukawa H, Wada H, Noguchi K, Shimamoto T, Yokota K. Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041). Cancer Chemother Pharmacol. 2017 Apr;79(4):651-660. doi: 10.1007/s00280-016-3237-x. Epub 2017 Mar 11.
PubMed 28283736
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of MK-3475 in Subjects With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT02180061
- Acronym / sponsor ID
- 3475-041
- Conditions
- Melanoma
- Keywords
- PD1, PD-1, PDL1, PD-L1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 15 Jul 2014 (actual)
- Primary completion
- 31 Aug 2017 (actual)
- Study completion
- 31 Aug 2017 (actual)
- First posted
- 2 Jul 2014 (estimated)
- Results
- Posted 4 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the safety, tolerability, and efficacy of every-3-week dosing (Q3W) of pembrolizumab (MK-3475) in participants with advanced melanoma; participants may receive pembrolizumab for up to 2 years if deriving clinical benefit. The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate.
Detailed description
Participants who discontinue pembrolizumab after achieving a complete response (CR) and subsequently develop progressive disease (PD) may be eligible to enter a Second Course Phase and receive pembrolizumab again.
The end of the study for each participant will occur with: 1) the marketing approval of pembrolizumab for melanoma, 2) the completion of safety follow up or 3) the time when a possibility of entry to second course of treatment is lost, whichever occurs last.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Advanced Cutaneous Melanoma | Experimental | Biological: PembrolizumabParticipants with advanced cutaneous melanoma received pembrolizumab, 2 mg/kg, intravenously (IV) over 30 minutes on Day 1 of each 3-week dosing cycle (Q3W). |
| Advanced Mucosal Melanoma | Experimental | Biological: PembrolizumabParticipants with advanced mucosal melanoma received pembrolizumab, 2 mg/kg, IV over 30 minutes on Day 1 Q3W. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- At least one measurable lesion
- Adequate organ function
Key exclusion criteria (13 listed)
- Prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent
- Is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5X half-life of the investigational compound, whichever is longer, of initial dosing on this study
- Chemotherapy, targeted small molecule therapy, radiotherapy, or biological cancer therapy (including monoclonal antibodies) within 4 weeks prior to the first dose of trial treatment, or not recovered (<= Grade 1 or baseline) from adverse events due to a previously administered agent
- Expected to require any other form of systemic or localized antineoplastic therapy while in study
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
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 |
|---|---|---|
| PembrolizumabAlso: MK-3475IV infusion | Biological | Advanced Cutaneous Melanoma, Advanced Mucosal Melanoma |
Primary outcome
Number of Participants Experiencing Adverse Events (AEs)
Time frame: All AEs: Up to 30 days after last dose of study drug; Serious AEs: Up to 90 days after last dose of study drug (Up to 27 months)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
Number of Participants Discontinuing Treatment Due to AEs
Time frame: Up to last dose of study drug (Up to 24 months)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
Overall Response Rate (ORR) Per Central Radiology Review Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: Up to 24 months
The ORR, using RECIST 1.1, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on central radiology review.
2 secondary outcomes
ORR Per Investigator Assessment Using RECIST 1.1
Time frame: Up to 24 months
ORR Per Central Radiology Review Using Immune-related Response Criteria (irRC)
Time frame: Up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28283736Yamazaki N, Takenouchi T, Fujimoto M, Ihn H, Uchi H, Inozume T, Kiyohara Y, Uhara H, Nakagawa K, Furukawa H, Wada H, Noguchi K, Shimamoto T, Yokota K. Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041). Cancer Chemother Pharmacol. 2017 Apr;79(4):651-660. doi: 10.1007/s00280-016-3237-x. Epub 2017 Mar 11.
- Merck Oncology Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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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.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab in people with Melanoma, run by Merck Sharp & Dohme LLC.
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 4 inclusion and 13 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 31 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 4 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Experiencing Adverse Events (AEs) (time frame: All AEs: Up to 30 days after last dose of study drug; Serious AEs: Up to 90 days after last dose of study drug (Up to 27 months)). 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 NCT02180061, 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 31 Mar 2020.