January 26, 2016
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February 11, 2016
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January 11, 2023
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April 12, 2016
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December 6, 2022 (Final data collection date for primary outcome measure)
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Determination of the recommended Phase 2 dose of CMP-001 when given in combination with pembrolizumab in subjects with advanced melanoma. [ Time Frame: 18 Months ]
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- Part 1 Dose Escalation and Dose Expansion: Number of Participants With TEAEs [ Time Frame: From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (up to approximately 3.5 years) ]
TEAEs will be evaluated and assigned a grade using CTCAE version 5.0
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Oral Temperature [ Time Frame: From screening up to end of treatment (EOT) (up to approximately 3.5 years) ]
Oral temperature should be measured in supine or seated position, following at least 30 minutes of rest.
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Respiratory Rate [ Time Frame: From screening up to EOT (up to approximately 3.5 years) ]
Respiratory rate should be measured in supine or seated position, following at least 30 minutes of rest.
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Systolic and Diastolic Blood Pressure [ Time Frame: From screening up to EOT (up to approximately 3.5 years) ]
Blood pressure should be measured in supine or seated position, following at least 30 minutes of rest.
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Body Weight [ Time Frame: From screening up to EOT (up to approximately 3.5 years) ]
Physical examination included body weight measurement.
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Body Mass Index (BMI) [ Time Frame: From screening up to EOT (up to approximately 3.5 years) ]
Physical examination included BMI measurement.
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters [ Time Frame: From screening up to EOT (up to approximately 3.5 years) ]
ECG parameters will include heart rate and PR, QRS, QT, and QT corrected for heart rate (QTc) intervals. QT will be corrected using Fridericia's (QTcF) formula. ECG will be performed after the participant has been resting in supine or semi-supine position for at least 5 minutes.
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters [ Time Frame: From screening up to EOT (up to approximately 3.5 years) ]
Clinical laboratory parameters includes serum chemistry, hematology, and urinalysis.
- Part 1 Dose Escalation: Concentration of Chemokine IP-10 [ Time Frame: Schedule A: Screening, Day 1 of Weeks 1, 3, 7, and Day 2 of Weeks 3, 7; Schedule B: Screening, Day 1 of Weeks 1, 5, 17, and Day 2 of Weeks 5, 17 ]
- Part 1 and Part 2: Objective Response Rate (ORR) (Percentage of Participants With Objective Response) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Using Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) Scans [ Time Frame: Baseline until confirmed disease progression (CR or PR) or death, whichever occur first (assessment at every 12 weeks throughout the study from Week 1 Day 1, up to approximately 3.5 years) ]
ORR will be calculated as the number of participants with a confirmed complete response (CR) or partial response (PR) divided by the number of participants dosed.
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Progression-Free Survival (PFS) as per RECIST Version 1.1 Using CT or MRI Scans [ Time Frame: From first dose of CMP-001 until disease progression or death, whichever occur first (assessment at every 12 weeks throughout the study from Week 1 Day 1, up to approximately 3.5 years) ]
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Best Overall Response (BOR) Rate (Percentage of Participants With Best Objective Response of CR or PR) as per RECIST Version 1.1 Using CT or MRI Scans [ Time Frame: Baseline until confirmed disease progression (CR or PR) or death, whichever occur first (assessment at every 12 weeks throughout the study from Week 1 Day 1, up to approximately 3.5 years) ]
BOR will be calculated as the number of participants with best response of CR or PR divided by the number of participants dosed.
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Time to Response (TTR) as per RECIST Version 1.1 Using CT or MRI Scans [ Time Frame: From first dose of CMP-001 until disease progression or death, whichever occur first (assessment at every 12 weeks throughout the study from Week 1 Day 1, up to approximately 3.5 years) ]
- Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Duration of Response (DOR) as per RECIST Version 1.1 Using CT or MRI Scans [ Time Frame: From the date of first confirmed CR or PR until the first date of recurrent or progressive disease (assessment at every 12 weeks throughout the study from Week 1 Day 1, up to approximately 3.5 years) ]
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- Assessment of treatment-emergent adverse events (TEAEs), using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Consent through 30 days post End of Treatment Visit (7 days post following study completion). ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Assessment of oral temperature measured by degrees fahrenheit [ Time Frame: Screening (2 weeks pre Cycle 1, Day 1), Days 1, 2, 8, and 15 of Cycles 1, 2, 3, 5 and 7. Days 1, 8, and 15 of Cycles 4 and 6 and End of Treatment visit (7 days post following study completion). Each cycle is 3 weeks in duration. ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Assessment of respiratory rate measured by beats per minute [ Time Frame: Screening (2 weeks pre Cycle 1, Day 1), Days 1, 2, 8, and 15 of Cycles 1, 2, 3, 5 and 7. Days 1, 8, and 15 of Cycles 4 and 6 and End of Treatment visit (7 days post following study completion). Each cycle is 3 weeks in duration. ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Assessment of systolic and diastolic blood pressure [ Time Frame: Screening (2 weeks pre Cycle 1, Day 1), Days 1, 2, 8, and 15 of Cycles 1, 2, 3, 5 and 7. Days 1, 8, and 15 of Cycles 4 and 6 and End of Treatment visit (7 days post following study completion). Each cycle is 3 weeks in duration. ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Assessment of weight measured by kilograms (kg) [ Time Frame: Screening (2 weeks pre Cycle 1, Day 1), Day 1 of Cycles 1, 2, 3, 5, and End of Treatment Visit (7 days post following study completion). ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Assessment of Body Mass Index (BMI) measured by kg/m2 [ Time Frame: Screening (2 weeks pre Cycle 1, Day 1), Day 1 of Cycles 1, 2, 3, 5, and End of Treatment Visit (7 days post following study completion). Each cycle is 3 weeks in duration. ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Perform and assess results of 12 lead electrocardiograms (ECGs) [ Time Frame: Screening (2 weeks pre Cycle 1, Day 1), Day 1 of Cycles 1, 2, 3, 5, and 7 and End of Treatment Visit (7 days post following study completion). Each cycle is 3 weeks in duration. ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Assessment of clinical laboratory parameters (urinalysis) by urine sample analysis [ Time Frame: Screening (2 weeks pre Cycle 1, Day 1), Days 1, 8, and 15 of Cycles 1 and 2. Day 1 of Cycles 3 through 7 and End of Treatment Visit (7 days post following study completion). Each cycle is 3 weeks in duration. ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Assessment of clinical laboratory parameters (chemistry and hematology) through blood sample analysis [ Time Frame: Screening (2 weeks pre Cycle 1, Day 1), Days 1, 8, and 15 of Cycles 1 and 2. Day 1 of Cycles 3 through 7 and End of Treatment Visit (7 days post following study completion). Each cycle is 3 weeks in duration. ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Assessment of of pregnancy status (women of childbearing potential only) by urine sample [ Time Frame: Screening (2 weeks pre Cycle 1, Day 1), Days 1 of every Cycle and End of Treatment Visit (7 days post following study completion). Each cycle is 3 weeks in duration. ]
To assess and describe the safety profile of CMP-001 when given in conjunction with pembrolizumab
- Assessment of concentrations of the chemokine IP-10 in collected serum samples. [ Time Frame: Days 1 and 2 of Cycles 1, 2, 3, 5, 7. Each cycle is 3 weeks in duration. ]
To assess and describe the pharmacodynamic effects of the addition of CMP-001 to pembrolizumab on serum concentrations of chemokine IP-10
- Assessment of antitumor activity Response Evaluation Criteria In Solid Tumors (RECIST Version 1.1) using computerized tomography (CT) or magnetic resonance imaging (MRI) scans. [ Time Frame: Screening (2 week pre Cycle 1, Day 1) and every 12 weeks throughout study for up to 18 months. Each cycle is 3 weeks in duration. ]
To assess and describe preliminary evidence of antitumor activity for CMP-001 when combined with pembrolizumab
- Assessment of antitumor activity Immune-Related Response Criteria (irRC) using computerized tomography (CT) or magnetic resonance imaging (MRI) scans. [ Time Frame: Screening (2 week pre Cycle 1, Day 1) and every 12 weeks throughout study for up to 18 months. Each cycle is 3 weeks in duration. ]
To assess and describe preliminary evidence of antitumor activity for CMP-001 when combined with pembrolizumab
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Not Provided
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Not Provided
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Clinical Study of CMP-001 in Combination With Pembrolizumab or as a Monotherapy
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A Multicenter, Two Part Open-Label, Phase 1B Clinical Study of CMP-001 Administered Either in Combination With Pembrolizumab or as a Monotherapy in Subjects With Advanced Melanoma
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This study will be conducted in two parts: Part 1 will be conducted using a Dose Escalation and Expansion design. The Part 1 Dose Escalation Phase of this study will identify a safe and tolerable dose to be further evaluated in the Part 1 Dose Expansion phase. Part 2 of the study will be conducted in parallel with the Part 1 Dose Expansion Phase and will evaluate the safety and efficacy of CMP-001 when administered as a monotherapy. A Treatment Extension to assess the safety profile of CMP-001 when given in combination with pembrolizumab or as monotherapy will be available to those who are currently being treated in either Part 1 or Part 2 of this study at the time of protocol Amendment 9, v10.0.
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Former Sponsor Checkmate Pharmaceuticals
The primary objective of Part 1 of the study is to determine the recommended Phase 2 dose (RP2D) and schedule of CMP-001 when given in combination with pembrolizumab in participants with advanced melanoma.
The primary objective of Part 2 of the study is to assess and describe the safety profile of CMP-001 when administered as monotherapy.
The primary objective of the Treatment Extension is to assess the safety profile of CMP-001 when given in combination with pembrolizumab or as monotherapy in the Treatment Extension.
Participants enrolled into either Part 1 or Part 2 will continue study treatment as long as they do not experience unacceptable toxicities and when continued treatment, is in the participant's best interest according to the Investigator. Participants may continue therapy beyond progression based upon Investigator judgement of potential benefit.
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Interventional
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Phase 1
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Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment
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Melanoma
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- Experimental: Part 1: Dose-Escalation - CMP-001 and Pembrolizumab
Participants will receive up to 5 escalating dose levels (1 milligram [mg], 3 mg, 5 mg, 7.5 mg and 10 mg) of CMP-001 via intratumoral injection according to one of 2 schedules (Schedule A: once weekly for 7 weeks, followed by every 3 weeks thereafter until participant is discontinued; Schedule B: once weekly for 2 weeks, followed by every 3 weeks thereafter until participant is discontinued) in combination with pembrolizumab at its labelled dose and schedule.
Interventions:
- Drug: CMP-001
- Drug: Pembrolizumab
- Experimental: Part 1: Dose-Expansion - CMP-001 and Pembrolizumab
Participants will receive CMP-001 10 mg via intratumoral injection by Schedule A (once weekly for 7 weeks, followed by every 3 weeks thereafter until participant is discontinued) in combination with pembrolizumab at its labelled dose and schedule. As of 05 October 2018, the dose and schedule for Part 1 Dose Expansion Phase was selected based on all available safety, efficacy and pharmacodynamic data from the Part 1 Dose Escalation Phase. Participants who were enrolled prior to 05 October 2018 to receive CMP-001 doses less than (<) 10 mg will have the option to receive CMP-001 doses up to 10 mg on Schedule A in combination with pembrolizumab.
Interventions:
- Drug: CMP-001
- Drug: Pembrolizumab
- Experimental: Part 2: CMP-001 Monotherapy and Crossover to Combination
Participants will receive CMP-001 10 mg via intratumoral injection by Schedule A (once weekly for 7 weeks, followed by every 3 weeks thereafter until participant is discontinued). Participants who were enrolled prior to 05 October 2018 to receive CMP-001 doses <10 mg will have the option to receive CMP-001 doses up to 10 mg on Schedule A. Participants with documented progression while on CMP-001 monotherapy treatment will have the option to crossover to the combination treatment of CMP-001 10 mg plus pembrolizumab, at the discretion of the Investigator.
Interventions:
- Drug: CMP-001
- Drug: Pembrolizumab
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Not Provided
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Completed
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199
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60
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December 6, 2022
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December 6, 2022 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- Histopathologically confirmed diagnosis of metastatic, or unresectable, malignant melanoma. Ocular melanoma participants are not eligible
- Participants who are currently receiving treatment with any anti-programmed cell death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) antibody, either alone or in combination and who are progressing. Participants must have received at least 4 doses of anti-PD-1/PD-L1 before enrolling into the CMP-001-001 study; or
- Participants who have previously received any anti-PD-1/PD-L1 therapy, alone or in combination and progressed, regardless of the best overall response to prior anti-PD-1/PD-L1 based therapy. Participants must have received at least 4 doses of anti-PD-1/PD-L1 (Inclusion criterion for Part 1 only)
- Participants must have at least one tumor lesion with a longest diameter of greater than or equal to (>=)0.5 centimeter (cm) that can be easily palpated or detected by ultrasound to facilitate intratumoral injection of CMP-001 (that is [i.e.], tumor in skin, muscle, subcutaneous tissue or accessible lymph node)
- Participants must have measurable disease by RECIST version 1.1.
- Capable of understanding and complying with protocol requirements
- A life expectancy of greater than 24 weeks at Screening
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Most recent laboratory values (within 3 weeks prior to Week 1 Day 1) before study entry meet the following standards:
- Bone marrow function: neutrophil count >=1,000/cubic millimeter (mm^3); platelet count >=75,000/mm^3 and hemoglobin concentration >8.0 grams per deciliter (g/dL).
- Liver function: total bilirubin less than or equal to (<=) 1.5 times the upper limit of normal (ULN) ranges of each institution, with the following exception: participants with Gilbert Disease serum bilirubin > 3*ULN; and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=3 times the ULN range of each institution
- Lactate dehydrogenase (LDH) <=2.0 times the ULN range of each institution
- Renal function: serum creatinine <=1.5 times the ULN range of each institution
- The participant must sign a written informed consent form prior to the initiation of any study procedures. Adult participants unable to provide written informed consent on their own behalf will not be eligible for the study
Part 1 Dose Expansion Phase participants must also meet the following inclusion criterion:
• At least one additional lesion that is measurable and is not intended for injection (to allow an assessment of systemic antitumor effect). These lesions not intended for injection may be located in any metastatic site.
Exclusion Criteria:
Main Criteria for Inclusion: Treatment Extension (CMP-001 alone or in combination with pembrolizumab)
- Actively being treated in either Part 1 or Part 2 of this study.
- Subject has signed an additional written ICF for Protocol Amendment 9 (v10.0) prior to receiving the first dose of CMP-001 and/or pembrolizumab in the Treatment Extension. Adult subjects unable to provide written informed consent on their own behalf will not be eligible for the study.
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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United States
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NCT02680184
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CMP-001-001
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No
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Not Provided
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Plan to Share IPD: |
Yes |
Plan Description: |
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing |
Supporting Materials: |
Study Protocol |
Supporting Materials: |
Statistical Analysis Plan (SAP) |
Supporting Materials: |
Informed Consent Form (ICF) |
Supporting Materials: |
Clinical Study Report (CSR) |
Supporting Materials: |
Analytic Code |
Time Frame: |
When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy. |
Access Criteria: |
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf |
URL: |
https://vivli.org/ |
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Regeneron Pharmaceuticals
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Checkmate Pharmaceuticals
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Regeneron Pharmaceuticals
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Checkmate Pharmaceuticals
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Not Provided
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Study Director: |
Clinical Trial Management |
Regeneron Pharmaceuticals |
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Regeneron Pharmaceuticals
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January 2023
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