Clinical Trials /

Clinical Study of CMP-001 in Combination With Pembrolizumab or as a Monotherapy

NCT02680184

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Clinical Study of CMP-001 in Combination With Pembrolizumab or as a Monotherapy
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CMP-001-001
  • NCT ID: NCT02680184

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
CMP-001QbG10, CYT003Part 1: Dose-Escalation - CMP-001 and Pembrolizumab
PembrolizumabKeytrudaPart 1: Dose-Escalation - CMP-001 and Pembrolizumab

Purpose

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.

Detailed Description

      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.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose-Escalation - CMP-001 and PembrolizumabExperimentalParticipants 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.
  • CMP-001
  • Pembrolizumab
Part 1: Dose-Expansion - CMP-001 and PembrolizumabExperimentalParticipants 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.
  • CMP-001
  • Pembrolizumab
Part 2: CMP-001 Monotherapy and Crossover to CombinationExperimentalParticipants 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.
  • CMP-001
  • Pembrolizumab

Eligibility Criteria

        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

             o 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:

          -  Pregnant or breastfeeding

          -  Received investigational therapy (that is, small molecule or biologic) within 30 days
             prior to the start of CMP-001 dosing on Week 1 Day 1. Received prior therapy with
             anti- cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody within 30
             days (within 45 days for Part 2 participants) prior to the start of CMP-001 dosing on
             Week 1 Day 1. However, if an investigational therapy has a short half-life, a reduced
             wash out period may be acceptable with Sponsor approval

          -  Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or
             hepatitis C virus (HCV). If there is no known or documented history of HIV, Hepatitis
             B or Hepatitis C, the site is not required to do additional testing for these values
             at Screening

          -  Developed autoimmune disorders of Grade 4 while on prior immunotherapy (Exclusion
             criterion for Part 1 only). Participants who developed autoimmune disorders of Grade
             <=3 may enroll if the disorder has resolved to Grade <=1 and the participant has been
             off systemic steroids at doses > 10 milligrams per day (mg/day) for at least two weeks

          -  Require systemic pharmacologic doses of corticosteroids greater than the equivalent of
             10 mg/day prednisone; replacement doses, topical, ophthalmologic and inhalational
             steroids are permitted. Participants who have a history of adrenal insufficiency and
             are receiving greater than 10 mg/day corticosteroid may be eligible but only after
             Sponsor consultation. Participants who are currently receiving steroids at a dose of
             <=10 mg/day do not need to discontinue steroids prior to enrollment

          -  Active (i.e., symptomatic or growing) central nervous system (CNS) metastases. However
             participants with active CNS metastases are eligible for the trial if

               -  the metastases have been treated by surgery and/or radiotherapy,

               -  the participant is off corticosteroids >10 mg/day and is neurologically stable
                  for at least 2 weeks prior to Screening

               -  brain imaging (by CT, positron emission tomography [PET], MRI, or per site
                  standards) completed within 3 months of screening (required for all participants)

          -  Any concurrent uncontrolled illness, including mental illness or substance abuse,
             which in the opinion of the Investigator, would make the participant unable to
             cooperate or participate in the trial

          -  Severe uncontrolled cardiac disease within 6 months of Screening, including but not
             limited to uncontrolled hypertension; unstable angina; myocardial infarction (MI) or
             cerebrovascular accident (CVA)

          -  Requires prohibited treatment (i.e., non-protocol specified anticancer
             pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant
             tumor)

          -  Women of child-bearing potential who are unable or unwilling to use an acceptable
             method of contraception
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Dose-Escalation Phase: RP2D of CMP-001 When Given in Combination With Pembrolizumab
Time Frame:21 days (for Schedule A dosing) and 35 days (for Schedule B dosing)
Safety Issue:
Description:TEAEs will be evaluated and assigned a grade using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:TEAEs will be evaluated and assigned a grade using CTCAE version 5.0
Measure: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)
Safety Issue:
Description:Oral temperature should be measured in supine or seated position, following at least 30 minutes of rest.
Measure: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)
Safety Issue:
Description:Respiratory rate should be measured in supine or seated position, following at least 30 minutes of rest.
Measure: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)
Safety Issue:
Description:Blood pressure should be measured in supine or seated position, following at least 30 minutes of rest.
Measure: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)
Safety Issue:
Description:Physical examination included body weight measurement.
Measure: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)
Safety Issue:
Description:Physical examination included BMI measurement.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:Clinical laboratory parameters includes serum chemistry, hematology, and urinalysis.
Measure: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
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:BOR will be calculated as the number of participants with best response of CR or PR divided by the number of participants dosed.
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Checkmate Pharmaceuticals

Trial Keywords

  • Malignant Melanoma
  • Stage IV Skin Melanoma

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