A Phase Ib Study of Pembrolizumab (MK-3475) in Chinese Subjects With Locally Advanced or Metastatic Melanoma (Keynote-151)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Melanoma
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 103
- Primary Endpoint
- Number of Participants Who Discontinued Study Treatment Due to an AE
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to determine the safety, tolerability, and objective response rate (ORR) of pembrolizumab (MK-3475) in Chinese participants with locally advanced or metastatic melanoma, with disease progression following first line chemotherapy or targeted therapy. ORR will be based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
With Amendment 6 (effective date 18-Mar-2022), once the study objectives have been met or the study has ended, participants will be discontinued from this study and may be enrolled in an extension study to continue protocol-defined assessments and treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is of the Chinese descent, was born in China, and has a Chinese home address.
- •Has histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy.
- •Participant may not have a diagnosis of uveal or ocular melanoma.
- •Overall proportion of participants with mucosa melanoma will be no more than 22%.
- •Has failed the first line chemotherapy (excluding adjuvant or neoadjuvant therapy) or targeted therapy for melanoma.
- •Has at least one measurable lesion as defined by RECIST 1.1 on imaging studies (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]).
- •Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- •Has an anticipated life expectancy of at least 3 months.
- •Demonstrates adequate organ function.
- •Has provided tissue for anti-programmed cell death ligand-1 (PD-L1) expression evaluation from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
Exclusion Criteria
- •Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD-L1, anti-PD-L2 agents.
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug.
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or baseline) from AEs due to agents administered more than 4 weeks earlier.
- •Has had chemotherapy, targeted small molecule therapy, radiotherapy within 2 weeks prior to the first dose of study drug, or who has not recovered (i.e., ≤ Grade 1 or baseline) from AEs due to a previously administered agent.
- •Has a known history of another (including unknown primary) malignancy within 5 years prior to first dose of study drug. (Exceptions include adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, superficial bladder cancer, or cancer in situ which has undergone potentially curative therapy.)
- •Is expected to require any other form of systemic or localized antineoplastic therapy while in study.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- •Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study drug.
- •Has an active infection requiring intravenous systemic therapy.
Outcomes
Primary Outcomes
Number of Participants Who Discontinued Study Treatment Due to an AE
Time Frame: Up to approximately 17 months (through data cutoff date of 27-December-2017)
The number of all participants who discontinued study treatment due to an AE is presented.
Number of Participants Who Experienced At Least One Adverse Event (AE)
Time Frame: Up to approximately 17 months (Through data cutoff date of 27-December-2017)
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: Up to approximately 17 months (through data cutoff date of 27-December-2017)
ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 assessed by blinded independent central review (BICR). The ORR per RECIST 1.1 for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants.
Secondary Outcomes
- Overall Survival (OS)(Up to approximately 76 months)
- Duration of Response (DOR) by Immune-related Response Evaluation Criteria in Solid Tumors Version (irRECIST)(Up to approximately 76 months)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 2 (21-day Cycle)(Day 21: Prior to the Cycle 2 (21-day cycle) Dose)
- Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 1 (21-day Cycle)(Day 0: 30 minutes after the end of infusion during Cycle 1 (21-day cycle))
- Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 76 months)
- Objective Response Rate (ORR) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)(Up to approximately 76 months)
- Progression-free Survival (PFS) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)(Up to approximately 76 months)
- Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 76 months)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 6 (21-day Cycle)(Day 105: Prior to the Cycle 6 (21-day cycle) Dose)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 8 (21-day Cycle)(Day 147: Prior to the Cycle 8 (21-day cycle) Dose)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 16 (21-day Cycle)(Day 315: Prior to the Cycle 16 (21-day cycle) Dose)
- Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 8 (21-day Cycle)(Day 147: 30 minutes after the end of infusion during Cycle 8 (21-day cycle))
- Observed Serum Concentration of Pembrolizumab 14 Days After The End of Infusion During Cycle 1 (21-day Cycle)(Day 15: 14 days after the end of infusion during Cycle 1 (21-day cycle))
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 4 (21-day Cycle)(Day 63: Prior to the Cycle 4 (21-day cycle) Dose)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 12 (21-day Cycle)(Day 231: Prior to the Cycle 12 (21-day cycle) Dose)
- Observed Serum Concentration of Pembrolizumab 1 Day After The End of Infusion During Cycle 1 (21-day Cycle)(Day 2: 1 day after the end of infusion during Cycle 1 (21-day cycle))
- Observed Serum Concentration of Pembrolizumab 5 Days After The End of Infusion During Cycle 1 (21-day Cycle)(Day 6: 5 days after the end of infusion during Cycle 1 (21-day cycle))