Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:
Adil Daud

Description

Summary

A Multicenter, Two-Part, Open-Label, Phase 1b Clinical Study of CMP-001 in Combination with Pembrolizumab or as a Monotherapy in Subjects with Advanced Melanoma

Official Title

A Multicenter, Two-Part, Open-Label, Phase 1B Clinical Study of CMP-001 in Combination With Pembrolizumab or as a Monotherapy in Subjects With Advanced Melanoma

Details

Objectives:

Primary (Part 1):

• To determine the recommended Phase 2 dose of CMP-001 when given in combination with pembrolizumab in subjects with advanced melanoma.

Primary (Part 2):

• To assess and describe the safety profile of CMP-001 when administered as monotherapy

Methodology:

This is a multicenter, open-label, Phase 1b clinical study of intratumoral administration of CMP-001 in combination with pembrolizumab or as a monotherapy in subjects with advanced melanoma. The study will be conducted in two parts. Part 1 (CMP-001 + pembrolizumab) is comprised of two phases: 1) a Dose Escalation Phase and 2) a Dose Expansion Phase. Part 2 of the study is designed to assess the CMP-001 as a monotherapy.

The Part 1 Dose Escalation phase of the study will evaluate two treatment schedules of CMP-001 (at doses of 1 mg, 3 mg, 5 mg, 7.5 mg or 10 mg) administered in combination with pembrolizumab, designated as Schedule "A" or "B". There were 44 subjects enrolled into the Part 1 Dose Escalation phase of the study.

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses) then administered once every 3 weeks until discontinuation.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until discontinuation.

The Part 1 Dose Expansion phase of the study will evaluate the recommended Phase 2 dose (RP2D) of CMP-001 + pembrolizumab on treatment Schedule A. There will be a maximum of 80 subjects enrolled in the Part 1 Dose Expansion phase.

Part 2 will evaluate CMP-001 as a monotherapy on treatment Schedule A. If the subject progresses after 8 weeks of CMP-001 monotherapy treatment they have the option to crossover onto the combination treatment of CMP-001+ pembrolizumab. There will be a maximum of 20 subjects enrolled in Part 2.

There will be a maximum of 144 patients enrolled in this study.

Keywords

Stage IV Skin Melanoma Malignant melanoma Melanoma Pembrolizumab CMP-001 CMP-001 1 mg plus pembrolizumab CMP-001 3 mg plus pembrolizumab CMP-001 5 mg plus pembrolizumab CMP-001 7.5 mg plus pembrolizumab CMP-001 10 mg plus pembrolizumab

Eligibility

You can join if…

Open to people ages 18 years and up

Part 1 (CMP-001 + pembrolizumab):

  1. Histopathologically confirmed diagnosis of metastatic, or unresectable, malignant melanoma. Ocular melanoma subjects are not eligible.
  2. Male and female subjects age 18 or older

3a. Subjects who are currently receiving treatment with any anti-PD-1/PD-L1 antibody,either alone or in combination and who are progressing. Subjects must have received at least 4 doses of anti-PD-1/PD-L1 before enrolling into the CMP-001-001 study.

OR

3b. Subjects 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. Subjects must have received at least 4 doses of anti-PD-1/PD-L1.

  1. Subjects must have at least one tumor lesion with a longest diameter of ≥0.5 cm that can be easily palpated or detected by ultrasound to facilitate intratumoral injection of CMP-001 (i.e., tumor in skin, muscle, subcutaneous tissue or accessible lymph node).
  2. Subjects must have measurable disease by RECIST Version 1.1. 6. Capable of understanding and complying with protocol requirements. 7. A life expectancy of greater than 24 weeks at Screening. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 9.Most recent laboratory values (within 3 weeks prior to Week 1 Day 1 (W1D1)) before study entry meet the following standards:
  3. Bone marrow function: neutrophil count ≥1,000/mm3, platelet count ≥ 75,000/mm3 and hemoglobin concentration > 8.0 g/dL.
  4. Liver function: total bilirubin ≤ 1.5 times the upper limit of normal (ULN) ranges of each institution, with the following exception: patients with Gilbert Disease serum bilirubin > 3X ULN AND aspartate aminotransferase (AST) and alanine aminotransferase(ALT) ≤ 3 times the ULN range of each institution.
  5. LDH ≤2.0 times the ULN range of each institution
  6. Renal function: serum creatinine ≤ 1.5 times the ULN range of each institution. 10.The subject must sign a written informed consent form prior to the initiation of any study procedures. Adult subjects unable to provide written informed consent on their own behalf will not be eligible for the study.

Part 1 Dose Expansion Phase subjects must also meet the following inclusion criterion:

  1. . 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.

You CAN'T join if...

Part 1 (CMP-001 + pembrolizumab):

  1. Pregnant or breastfeeding.
  2. Received investigational therapy (e.g. small molecule or biologic) within 30 days prior to the start of CMP-001 dosing on W1D1. However, if an investigational therapy has a short half-life, a reduced wash out period may be acceptable with Sponsor approval.
  3. Received treatment with anti-CTLA-4 antibody within 30 days prior to the start of CMP-001 dosing on W1D1.
  4. 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.
  5. Developed autoimmune disorders of Grade 4 while on prior immunotherapy. Subjects who developed autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤ 1 and the subject has been off systemic steroids at doses > 10mg/day for at least two weeks.
  6. Require systemic pharmacologic doses of corticosteroids greater than the equivalent of 10 mg/day; replacement doses, topical, ophthalmologic and inhalational steroids are permitted. Subjects who have a history of adrenal insufficiency and are receiving greater than 10 mg/day coticosteroid may be eligible but only after Sponsor consultation. Subjects who are currently receiving steroids at a dose of ≤10 mg/day do not need to discontinue steroids prior to enrollment.
  7. Active (i.e., symptomatic or growing) central nervous system (CNS) metastases. However subjects with active CNS metastases are eligible for the trial if
  8. the metastases have been treated by surgery and/or radiotherapy,
  9. the subject is off corticosteroids > 10 mg/day and is neurologically stable for at least 2 weeks prior to Screening.
  10. brain MRI completed within 3 months of screening (required for all subjects).
  11. Any concurrent uncontrolled illness, including mental illness or substance abuse,which in the opinion of the Investigator, would make the subject unable to cooperate or participate in the trial.
  12. 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).
  13. . Requires prohibited treatment (i.e., non-protocol specified anticancer pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant tumor).
  14. . Women of child-bearing potential who are unable or unwilling to use an acceptable method of contraception.

Inclusion Criteria - Part 2: CMP-001 Monotherapy

Subjects must meet all of the following inclusion criteria to be eligible:

  1. Histopathologically confirmed diagnosis of metastatic, or unresectable, malignant melanoma. Ocular melanoma subjects are not eligible.
  2. Male or female subjects age 18 or older.
  3. Previously received any anti-PD-1/PD-L1 therapy, alone or in combination. Subjects must have received a minimum of 4 doses of anti-PD-1/PD-L1 therapy prior to study entry.
  4. Subjects must have at least one tumor lesion with a longest diameter of ≥0.5 cm that can be easily palpated or detected by ultrasound to facilitate intratumoral injection of CMP-001 (i.e., tumor in skin, muscle, subcutaneous tissue or accessible lymph node).
  5. Subjects must have measurable disease by RECIST Version 1.1.
  6. Capable of understanding and complying with protocol requirements.
  7. A life expectancy of greater than 24 weeks at Screening.
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
  9. Most recent laboratory values (within 3 weeks prior to first CMP-001 injection at Week 1 Day 1 (W1D1)) before study entry meet the following standards:
  10. Bone marrow function: neutrophil count ≥1,000/mm3, platelet count ≥75,000/mm3 and hemoglobin concentration > 8.0 g/dL.
  11. Liver function: total bilirubin ≤ 1.5 times the upper limit of normal (ULN)ranges of each institution, aspartate aminotransferase and alanine aminotransferase ≤ 3 times the ULN range of each institution.
  12. LDH ≤2.0 times the ULN range of each institution.
  13. Renal function: serum creatinine ≤1.5 times the ULN range of each institution.
  14. . The subject must sign a written informed consent form prior to the initiation of any study procedures. Adult subjects unable to provide written informed consent on their own behalf will not be eligible for the study.

Exclusion Criteria Part 2: (CMP-001 Monotherapy)

  1. Pregnant or breastfeeding.
  2. Received investigational therapy (e.g. small molecule or biologic) within 30 days prior to the start of CMP-001 dosing on W1D1. Received prior therapy with an anti-PD1/PD-L1 or anti-CTLA-4 within 45 days prior to the start of CMP-001 dosing on W1D1. However, if an investigational therapy has a short half-life, a reduced wash out period may be acceptable with Sponsor approval.
  3. 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.
  4. Subjects who developed autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤1 and the subject has been off systemic steroids at doses >10 mg/day for at least 2 weeks.
  5. Require systemic pharmacologic doses of corticosteroids greater than the equivalent of 10 mg/d; replacement doses, topical, ophthalmologic and inhalational steroids are permitted. Subjects who have a history of adrenal insufficiency and are receiving greater than 10 mg/day of corticosteroid may be eligible but only after Sponsor consultation. Subjects who are currently receiving steroids at a dose of ≤ 10 mg/day do not need to discontinue steroids prior to enrollment.
  6. Active (i.e., symptomatic or growing) central nervous system (CNS) metastases.

However, subjects with active CNS metastases are eligible for the trial if:

  • the metastases have been treated by surgery and/or radiotherapy.
  • the subject is off corticosteroids >10 mg/day and is neurologically stable for at least 2 weeks prior to Screening.
  • brain MRI completed within 3 months of screening (required for all subjects).
  • Any concurrent uncontrolled illness, including mental illness or substance abuse,which in the opinion of the Investigator, would make the subject 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 childbearing potential who are unable or unwilling to use an acceptable method of contraception.

Locations

  • UCSF Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco California 94115 United States
  • University of California, Los Angeles accepting new patients
    Los Angeles California 90095 United States
  • City of Hope National Medical Center accepting new patients
    Duarte California 91010 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Checkmate Pharmaceuticals
ID
NCT02680184
Phase
Phase 1
Lead Scientist
Adil Daud
Study Type
Interventional
Last Updated
June 17, 2018