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.
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.
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:
- 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
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.
