CMP-001 in Combination With Nivolumab Compared to Nivolumab Monotherapy in Subjects With Advanced Melanoma

A Randomized, Open-label, Active-control, Phase 2/3 Study of First-line Intratumoral CMP-001 in Combination With Intravenous Nivolumab Compared to Nivolumab Monotherapy in Subjects With Unresectable or Metastatic Melanoma

CMP-001-011 is a Phase 2/3 study of CMP-001 intratumoral (IT) and nivolumab intravenous (IV) compared to nivolumab monotherapy administered to participants with unresectable or metastatic melanoma.

The study is divided into two phases: Phase 2 and Phase 3.

The primary objective of Phase 2 of the study is to determine confirmed objective response rate (ORR) for treatment with first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy in subjects with unresectable or metastatic melanoma.

The secondary objective of Phase 2 of the study is to evaluate the safety and tolerability of first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy in subjects with unresectable or metastatic melanoma.

The primary objective of Phase 3 of the study is to evaluate progression-free survival (PFS) for subjects receiving first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy for unresectable or metastatic melanoma.

The secondary objectives of Phase 3 are to:

• To evaluate the safety and tolerability of first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy in subjects with unresectable or metastatic melanoma.
• To evaluate the efficacy of first-line CMP-001 in combination with nivolumab versus nivolumab monotherapy in subjects with unresectable or metastatic melanoma.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Metastatic Melanoma; Unresectable Melanoma; Advanced Melanoma
• Intervention / Treatment: Drug: CMP-001; Drug: Nivolumab

Detailed Description

Former Sponsor Checkmate Pharmaceuticals

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at UC San Diego Health
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • Newport Beach, California, United States, 92663
      • USC Norris Oncology/Hematology-Newport Beach
    • San Marcos, California, United States, 92069
      • California Cancer Associates for Research & Excellence, Inc.
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Hartford Healthcare
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Health Care
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center / Hillman Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology, Sammons Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CMP-001 and Nivolumab; All enrolled subjects will receive CMP-001 IT and nivolumab IV according to the treatment schedule until a reason for treatment discontinuation is reached.	Drug: CMP-001; Subjects will receive CMP-001 10 mg IT weekly for 7 doses after which CMP-001 will be administered every 3 weeks (Q3W).; Other Names: vidutolimod; Drug: Nivolumab; Nivolumab 360 mg IV is administered Q3W.; Other Names: OPDIVO
Experimental: Nivolumab Monotherapy; All enrolled subjects will receive nivolumab monotherapy IV according to the treatment schedule until a reason for treatment discontinuation is reached.	Drug: Nivolumab; Nivolumab 360 mg IV is administered Q3W.; Other Names: OPDIVO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR)	ORR, defined as the percentage of participants who have confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST vl.l) as assessed by Blinded Independent Central Review (BICR)	Up to approximately 39 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death	Number of participants with any treatment-emergent adverse event (TEAE), any serious TEAE, and any TEAE leading to discontinuation or death reported.	Up to approximately 28 months (122 weeks)
Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)	Number of participants per NCI CTCAE version 5.0 Adverse Event Grade reported: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2 Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limited self-care activities of daily living; Grade 4 Life-threatening consequences: urgent intervention indicated; Grade 5 Death related to adverse event.	Up to approximately 28 months (122 weeks)
Time to Response (TTR) by BICR	TTR, defined as the time from the date of randomization to the first time when criteria are first met for complete response (CR) or partial response (PR), whichever occurred first, per RECIST vl.1 by BICR.	Up to approximately 39 months
Time to Response (TTR) by Investigator	TTR, defined as the time from the date of randomization to the first time when criteria are first met for CR or PR, whichever occurred first, per RECIST vl.1 by Investigator.	Up to approximately 39 months
Duration of Response (DOR) by BICR	DOR, defined as time from the date of first documented response (CR or PR) to the date of documented progressive disease (PD), based on RECIST vl.1 by BICR or death, whichever occurred first.	Up to approximately 39 months
Duration of Response (DOR) by Investigator	DOR, defined as time from the date of first documented response (CR or PR) to the date of documented progressive disease (PD), based on RECIST vl.1 by Investigator or death, whichever occurred first.	Up to approximately 39 months
Confirmed ORR in Non-injected Target Lesions by Investigator	Confirmed ORR, defined as the percentage of participants in the analysis set who had confirmed BOR of CR or PR based on RECIST vl.1 as assessed by Investigator.	Up to approximately 39 months
Progression-free Survival (PFS) by BICR	PFS, defined as the time from the date of randomization to date of documented PD based on RECIST vl.1 by BICR or death, whichever occurred first.	Up to approximately 39 months
Progression-free Survival (PFS) by Investigator	PFS, defined as the time from the date of randomization to date of documented PD based on RECIST vl.1 by Investigator or death, whichever occurred first.	Up to approximately 39 months
Overall Survival (OS) by Investigator	OS, defined as the time from the date of randomization to the date of death from any cause.	Up to approximately 40 months (174 weeks)

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Actual): July 22, 2024
• Study Completion (Actual): July 22, 2024

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: January 4, 2021
• First Posted (Actual): January 6, 2021

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: August 15, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: vidutolimod
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: CMP-001-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No