Melanoma
Conditions
Keywords
PD1, PD-1, PDL1, PD-L1
Brief 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. 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.
Interventions
BIOLOGICALPembrolizumab
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Adverse Events (AEs) | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR Per Investigator Assessment Using RECIST 1.1 | Up to 24 months | 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. |
| ORR Per Central Radiology Review Using Immune-related Response Criteria (irRC) | Up to 24 months | 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. |
Participant flow
Pre-assignment details
These results include data received prior to the safety database cutoff date of 23-Oct-2017.
Participants by arm
| Arm | Count |
|---|---|
| Advanced Cutaneous Melanoma Participants with advanced cutaneous melanoma received pembrolizumab, 2 mg/kg, IV over 30 minutes on Day 1 Q3W. | 34 |
| Advanced Mucosal Melanoma Participants with advanced mucosal melanoma received pembrolizumab, 2 mg/kg, IV over 30 minutes on Day 1 Q3W. | 8 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Clinical Progression | 5 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progressive Disease | 15 | 5 |
Baseline characteristics
| Characteristic | Advanced Mucosal Melanoma | Total | Advanced Cutaneous Melanoma |
|---|---|---|---|
| Age, Continuous | 58.6 Years STANDARD_DEVIATION 15.5 | 63.6 Years STANDARD_DEVIATION 13.8 | 64.8 Years STANDARD_DEVIATION 13.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 42 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 42 Participants | 34 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 16 Participants | 13 Participants |
| Sex: Female, Male Male | 5 Participants | 26 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 34 | 1 / 8 |
| other Total, other adverse events | 34 / 34 | 8 / 8 |
| serious Total, serious adverse events | 13 / 34 | 4 / 8 |
Outcome results
Primary
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.
Time frame: Up to last dose of study drug (Up to 24 months)
Population: The APaT population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Advanced Cutaneous Melanoma | Number of Participants Discontinuing Treatment Due to AEs | 5 Participants |
| Advanced Mucosal Melanoma | Number of Participants Discontinuing Treatment Due to AEs | 2 Participants |
Primary
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.
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)
Population: The All Participants as Treated (APaT) population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Advanced Cutaneous Melanoma | Number of Participants Experiencing Adverse Events (AEs) | 34 Participants |
| Advanced Mucosal Melanoma | Number of Participants Experiencing Adverse Events (AEs) | 8 Participants |
Primary
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.
Time frame: Up to 24 months
Population: The Full Analysis Set (FAS) population consisted of all allocated participants who had measurable lesions at the Baseline scan as assessed by central radiology review and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Advanced Cutaneous Melanoma | Overall Response Rate (ORR) Per Central Radiology Review Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 24.1 Percentage of Participants |
| Advanced Mucosal Melanoma | Overall Response Rate (ORR) Per Central Radiology Review Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 25.0 Percentage of Participants |
p-value: 0.0216Exact Binomial Distribution
Secondary
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.
Time frame: Up to 24 months
Population: The FAS population consisted of all allocated participants who had irRC measurable lesions at the Baseline scan as assessed by central radiology review and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Advanced Cutaneous Melanoma | ORR Per Central Radiology Review Using Immune-related Response Criteria (irRC) | 30.4 Percentage of Participants |
| Advanced Mucosal Melanoma | ORR Per Central Radiology Review Using Immune-related Response Criteria (irRC) | 25.0 Percentage of Participants |
Secondary
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.
Time frame: Up to 24 months
Population: The FAS population consisted of all allocated participants who had measurable lesions at the Baseline scan as assessed by Investigator review and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Advanced Cutaneous Melanoma | ORR Per Investigator Assessment Using RECIST 1.1 | 29.4 Percentage of Participants |
| Advanced Mucosal Melanoma | ORR Per Investigator Assessment Using RECIST 1.1 | 37.5 Percentage of Participants |