Inclusion Criteria:
Subjects enrolled in the study must meet all of the following inclusion criteria to be
eligible:
1. Histologically or cytologically confirmed unresectable Stage III or Stage IV melanoma
per AJCC Cancer Staging Manual Eighth Edition.
2. Measurable disease, as defined by RECIST v1.1 and both of the following:
1. At least 1 accessible lesion amenable to repeated IT injection
2. One or more measurable lesions at least 1 cm in diameter that are not intended
for CMP-001 injection and can be followed as target lesions per RECIST v1.1
3. Able to provide tissue from a core or excisional biopsy (fine needle aspirate is not
sufficient). A newly obtained biopsy (within 90 days before the first dose of study
treatment) is preferred, but an archival sample is acceptable if no intervening
therapy for melanoma/cancer was received. Note: for tissue sampling details, please
refer to the Laboratory Manual.
4. Adequate organ function based on most recent laboratory values within 3 weeks before
the first dose of study treatment on Week 1 Day 1 (W1D1):
1. Bone marrow function:
- neutrophil count ≥1500/mm3
- platelet count ≥ 100 000/mm3
- hemoglobin concentration ≥9 g/dL
- white blood cells ≥2000/mm3
2. Liver function:
- total bilirubin ≤1.5 × the upper limit of normal (ULN) with the following
exception: subjects with Gilbert Disease total serum bilirubin ≤3 × ULN
- aspartate aminotransferase and alanine aminotransferase ≤3 ×ULN
3. Lactate dehydrogenase ≤2 × ULN
4. Renal function: estimated (Cockcroft-Gault) or measured creatinine clearance ≥30
mL/min
5. Coagulation
- International normalized ratio or prothrombin time (PT) ≤ 1.5 × ULN, unless
subject is receiving anticoagulant therapy, as long as PT or partial
thromboplastin time (PTT) is within therapeutic range of intended use of
anticoagulants
- Activated partial thromboplastin time or PTT ≤1.5 × ULN, unless subject is
receiving anticoagulant therapy, as long as PT or PTT is within therapeutic
range of intended use of anticoagulants
5. Eastern Cooperative Oncology Group Performance Status of 0 to 1 at Screening.
6. Age ≥18 years at time of consent.
7. Capable of understanding and complying with protocol requirements.
8. Women of childbearing potential must have negative serum pregnancy test prior to
dosing at W1D1 and be willing to use an adequate method of contraception from the time
of consent until at least 150 days after the last dose of study treatment.
9. Male subjects must be surgically sterile or must agree to use adequate method of
contraception from the time of consent until at least 210 days after the last dose of
study treatment.
10. Able and willing to provide written informed consent and to follow study instructions.
Subjects unable to provide written informed consent on their own behalf will not be
eligible for the study.
Exclusion Criteria:
Subjects presenting with any of the following will not qualify for entry into the study:
1. Uveal, acral, or mucosal melanoma.
2. Received prior systemic treatment for melanoma in the unresectable or metastatic
setting. Prior adjuvant therapy is acceptable if the treatment course (of
approximately 1 year duration) was completed and there was no recurrence within 6
months of the last dose of adjuvant treatment.
3. Received prior therapy with CMP-001.
4. Requires systemic pharmacologic doses of corticosteroids greater than the equivalent
of 10 mg/day prednisone within 30 days before the first dose of study treatment on
W1D1.
1. Subjects who are currently receiving steroids at a prednisone-equivalent dose of
≤10 mg/day do not need to discontinue steroids prior to enrollment.
2. Replacement doses, topical, ophthalmologic, and inhalational steroids are
permitted.
5. History of CTCAE v5.0 Grade 4 immune-related AE due to adjuvant CTLA-4 or PD-1
blocking antibody.
6. Not fully recovered from adverse events (to Grade 1 or less [per CTCAE v5.0], with the
exception of persistent alopecia, adrenal insufficiency, and hypothyroidism) due to
prior treatment.
7. Active pneumonitis, history of pneumonitis that required steroids, or history of
interstitial lung disease.
8. Severe uncontrolled cardiac disease within 6 months of Screening, including but not
limited to poorly controlled hypertension, unstable angina, myocardial infarction,
congestive heart failure (New York Heart Association Class II or greater),
pericarditis within the previous 6 months, cerebrovascular accident, and implanted or
continuous use of a pacemaker or defibrillator.
9. Known history of immunodeficiency.
10. Known additional malignancy that has progressed or required active treatment within
the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell
carcinoma of the skin that has undergone potentially curative therapy, curatively
treated localized prostate cancer with prostate-specific antigen level below 4.0
ng/mL, in situ cervical cancer on biopsy or a squamous intraepithelial lesion on
Papanicolaou smear, thyroid cancer (except anaplastic), and adjuvant hormonal therapy
for breast cancer >3 years from curative-intent surgical resection.
11. Active autoimmune disease that has required systemic treatment in past 2 years;
replacement therapy is not considered a form of systemic treatment.
12. Untreated, symptomatic, or enlarging central nervous system metastases or
carcinomatous meningitis (including leptomeningeal metastases from solid tumors).
13. Prior allogenic tissue/solid organ transplant.
14. Known or suspected active infection with severe acute respiratory syndrome coronavirus
2 virus (SARS-CoV-2).
15. Active infection requiring systemic therapy.
16. Known or suspected infection with HIV, hepatitis B virus, or hepatitis C virus;
testing is not required unless suspected.
17. Received a live/attenuated virus vaccination within 30 days prior to the first dose of
study treatment on W1D1.
18. Received blood products (including platelets or red blood cells) or colony stimulating
factors (including granulocyte colony stimulating factor, granulocyte/macrophage
colony stimulating factor, or recombinant erythropoietin) within 30 days prior to the
start of Screening.
19. History of allergy or hypersensitivity to nivolumab and/or any of its excipients.
20. 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.
21. Participation in another clinical study of an investigational anticancer therapy or
device within 30 days before the first dose of study treatment on W1D1.
Note: Participation in the follow-up phase (receiving no study treatment) of a prior
study is allowed.
22. Requires prohibited treatment (ie, non-protocol specified anticancer pharmacotherapy,
surgery, or radiotherapy) for treatment of malignant tumor.
23. Has a life expectancy of less than 3 months and/or has rapidly progressing disease
(eg, tumor bleeding, uncontrolled tumor pain) in the opinion of the treating
Investigator.
24. Pregnant or breast-feeding or expecting to conceive or donate eggs within the
projected duration of the study, from the time of consent until at least 150 days
after the last dose of study treatment for women.
