Clinical Trials /

Phase 1B Study Evaluating Alternative Routes of Administration of CMP-001 in Combination With Pembrolizumab in Participants With Advanced Melanoma

NCT03084640

Description:

CMP-001-002 is a Phase 1b study of CMP-001 administered to participants with advanced melanoma who are either receiving pembrolizumab, or who have previously received an anti-programmed cell death protein 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy for advanced melanoma, and who have not responded (that is, immunotherapy resistant). This study will be conducted in two parts: Part 1 will consist of a Dose Escalation Phase and a Dose Expansion Phase - Dose Escalation Phase will be conducted to assess and identify a recommended phase 2 dose (RP2D) of CMP-001 for subcutaneous (SC) administration - The Dose Expansion Phase is intended to further characterize the safety, pharmacodynamics, and preliminary evidence of antitumor activity of the RP2D of CMP-001 administered SC in combination with pembrolizumab Part 2 will assess the safety and preliminary evidence of antitumor activity of CMP-001, administered both SC and intratumoral (IT) when given in combination with pembrolizumab. Participants will continue treatment with CMP-001 in combination with pembrolizumab as long as they do not experience unacceptable toxicities and when continued treatment, is in the participant's best interest according to the Investigator.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1B Study Evaluating Alternative Routes of Administration of CMP-001 in Combination With Pembrolizumab in Participants With Advanced Melanoma
  • Official Title: A Multicenter, Two Part, Phase 1B Study Evaluating Alternative Routes of Administration of CMP-001 in Combination With Pembrolizumab in Subjects With Advanced Melanoma

Clinical Trial IDs

  • ORG STUDY ID: CMP-001-002
  • NCT ID: NCT03084640

Conditions

  • Malignant Melanoma

Interventions

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

Purpose

CMP-001-002 is a Phase 1b study of CMP-001 administered to participants with advanced melanoma who are either receiving pembrolizumab, or who have previously received an anti-programmed cell death protein 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy for advanced melanoma, and who have not responded (that is, immunotherapy resistant). This study will be conducted in two parts: Part 1 will consist of a Dose Escalation Phase and a Dose Expansion Phase - Dose Escalation Phase will be conducted to assess and identify a recommended phase 2 dose (RP2D) of CMP-001 for subcutaneous (SC) administration - The Dose Expansion Phase is intended to further characterize the safety, pharmacodynamics, and preliminary evidence of antitumor activity of the RP2D of CMP-001 administered SC in combination with pembrolizumab Part 2 will assess the safety and preliminary evidence of antitumor activity of CMP-001, administered both SC and intratumoral (IT) when given in combination with pembrolizumab. Participants will continue treatment with CMP-001 in combination with pembrolizumab as long as they do not experience unacceptable toxicities and when continued treatment, is in the participant's best interest according to the Investigator.

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose-Escalation - CMP-001 (SC) and PembrolizumabExperimentalParticipants will receive up to 3 escalating dose levels (5 milligrams [mg], 7.5 mg, and 10 mg) of CMP-001 via SC injection once a week for 3 weeks and every 3 weeks thereafter until discontinuation of treatment in combination with pembrolizumab at its labelled dose and schedule.
  • CMP-001
  • Pembrolizumab
Part 1: Dose-Expansion - CMP-001 (SC) and PembrolizumabExperimentalParticipants will receive RP2D (as determined in Part 1 dose-escalation phase) of CMP-001 via SC injection once a week for 3 weeks and every 3 weeks thereafter until discontinuation of treatment in combination with pembrolizumab at its labelled dose and schedule.
  • CMP-001
  • Pembrolizumab
Part 2: CMP-001 (SC and IT) and PembrolizumabExperimentalParticipants will receive CMP-001 via SC injection once weekly for 2 weeks, then IT injection once weekly for 4 weeks, and SC injection once weekly for every 3 weeks thereafter until discontinuation of treatment in combination with pembrolizumab at its labelled dose and schedule. CMP-001 planned IT dose level in Part 2 will be up to 10 mg and the SC dose will be the RP2D determined from Part 1 dose-escalation phase of the study.
  • CMP-001
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

        • Participants enrolled into Part 1 must have tumor lesions where repeated IT injections
        are not feasible and in whom,based on the Ivestigator's judgement, SC injection is the only
        viable route of CMP-001 administration. Participants with lesions that are easily
        accessible for IT injections are not eligible to participate in Part 1. Participants
        enrolled into Part 2 must have tumor lesions that are amenable to repeated IT injections.

        All participants enrolled into either Part 1 or Part 2 must meet all of the following
        inclusion criteria to be eligible:

          -  Histopathologically confirmed diagnosis of metastatic or unresectable malignant
             melanoma. Ocular melanoma participants are not eligible.

          -  Either a) Participants currently receiving treatment with the anti-PD-1 antibody
             pembrolizumab either alone or in combination. Participants must have a best response
             of either Stable Disease (SD) or Progressive Disease (PD) per RECIST Version 1.1 while
             on pembrolizumab.

               -  Participants who have had SD must have been on pembrolizumab for at least 12
                  weeks.

               -  There is no minimum treatment duration for participants who have PD while on
                  pembrolizumab.

          -  Or b) Participants who have previously received any anti-PD-1/PD-L1 therapy, alone or
             in combination, and who were deemed to have not responded (that is, best response of
             SD or PD) to this therapy/combination irrespective of the timing of the prior therapy
             relative to first dose of CMP-001.

          -  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) meet the
             following standards:

               1. Bone marrow function: neutrophil count greater than or equal to (>/=) 1,000/cubic
                  millimeter (mm^3), platelet count >/=75,000/mm^3 and hemoglobin concentration >/=
                  8.0 grams per deciliter (g/dL).

               2. Liver function: total bilirubin less than or equal to (<=) 1.5 times the upper
                  limit of normal (ULN) of each institution, aspartate aminotransferase and alanine
                  aminotransferase <=3 times the ULN range of each institution.

               3. Lactate dehydrogenase (LDH) <=2.0 times the ULN range of each institution.

               4. 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.

        Exclusion Criteria:

          -  Pregnant or breast feeding

          -  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. However, if an investigational
             drug has a short half-life, a reduced wash out period may be acceptable upon
             permission given by the Sponsor.

          -  Received treatment with anti- cytotoxic T-lymphocyte-associated protein 4
             (anti-CTLA-4) antibody within 30 days prior to the start of CMP-001 dosing on Week 1
             Day 1.

          -  Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or
             hepatitis C virus (HCV).

          -  Developed autoimmune disorders of Grade 4 while on prior immunotherapy. 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
             greater than (>) 10 milligrams per day (mg/day) for at least 2 weeks.

          -  Require systemic pharmacologic doses of corticosteroids at or above 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 systemic steroids 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 (that is, symptomatic or growing) central nervous system (CNS) metastases.
             Participants with CNS metastases are eligible for the trial if: a) the metastases have
             been treated by surgery and/or radiotherapy; b) the participant is off corticosteroids
             >10 mg/day and is neurologically stable for at least 2 weeks prior to Screening; c)
             brain MRI completed within 3 months of Screening.

          -  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 that is, 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 Administered SC and Given in Combination With Pembrolizumab
Time Frame:15 days from date of first CMP-001 injection (Week 1 Day 1)
Safety Issue:
Description:TEAEs will be evaluated 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 2.5 years)
Safety Issue:
Description:TEAEs will be evaluated using CTCAE version 5.0.
Measure:Part 1 Dose Escalation and Dose Expansion, and Part 2: Oral Temperature
Time Frame:From screening up to end of treatment (EOT) (up to approximately 2.5 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: Respiratory Rate
Time Frame:From screening up to EOT (up to approximately 2.5 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: Systolic and Diastolic Blood Pressure
Time Frame:From screening up to EOT (up to approximately 2.5 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: Body Weight
Time Frame:From screening up to EOT (up to approximately 2.5 years)
Safety Issue:
Description:Physical examination included body weight measurement.
Measure:Part 1 Dose Escalation and Dose Expansion, and Part 2: Body Mass Index (BMI)
Time Frame:From screening up to EOT (up to approximately 2.5 years)
Safety Issue:
Description:Physical examination included BMI measurement.
Measure:Part 1 Dose Escalation and Dose Expansion, and Part 2: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters
Time Frame:From screening up to EOT (up to approximately 2.5 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: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters
Time Frame:From screening up to EOT (up to approximately 2.5 years)
Safety Issue:
Description:Clinical laboratory parameters includes serum chemistry, hematology, urinalysis, coagulation and thyroid function tests.
Measure:Part 1 Dose Escalation: Concentration of Chemokine IP-10
Time Frame:Day 1 of Weeks 1, 3, 15 and Day 2 of Week 3, 15
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 2.5 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: 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 2.5 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: 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 2.5 years)
Safety Issue:
Description:
Measure:Part 1 Dose Escalation and Dose Expansion, and Part 2: 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 2.5 years)
Safety Issue:
Description:

Details

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

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