Clinical Study of CMP-001 in Combination With Pembrolizumab or as a Monotherapy

NCT02680184 | Completed Phase 1 FDA Drug

• 1 other identifier: CMP-001-001
• Study Type: interventional
• Target: 199
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Melanoma

Keywords

Malignant Melanoma; Stage IV Skin Melanoma; vidutolimod

Outcome Measures

Primary Outcomes (2)

• Part 1: Dose-Escalation Phase: RP2D of CMP-001 When Given in Combination With Pembrolizumab

  21 days (for Schedule A dosing) and 35 days (for Schedule B dosing)

• Part 2 Monotherapy: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  TEAEs will be evaluated and assigned a grade using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (up to approximately 3.5 years)

Secondary Outcomes (14)

• Part 1 Dose Escalation and Dose Expansion: Number of Participants With TEAEs

  From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (up to approximately 3.5 years)

• Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Oral Temperature

  From screening up to end of treatment (EOT) (up to approximately 3.5 years)

• Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Respiratory Rate

  From screening up to EOT (up to approximately 3.5 years)

• Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Systolic and Diastolic Blood Pressure

  From screening up to EOT (up to approximately 3.5 years)

• Part 1 Dose Escalation and Dose Expansion, and Part 2 Monotherapy: Body Weight

  From screening up to EOT (up to approximately 3.5 years)

Study Arms (3)

Part 1: Dose-Escalation - CMP-001 and Pembrolizumab

EXPERIMENTAL

Participants will receive up to 5 escalating dose levels (1 milligram \[mg\], 3 mg, 5 mg, 7.5 mg and 10 mg) of CMP-001 via intratumoral injection according to one of 2 schedules (Schedule A: once weekly for 7 weeks, followed by every 3 weeks thereafter until participant is discontinued; Schedule B: once weekly for 2 weeks, followed by every 3 weeks thereafter until participant is discontinued) in combination with pembrolizumab at its labelled dose and schedule.

Drug: CMP-001; Drug: Pembrolizumab

Part 1: Dose-Expansion - CMP-001 and Pembrolizumab

EXPERIMENTAL

Participants will receive CMP-001 10 mg via intratumoral injection by Schedule A (once weekly for 7 weeks, followed by every 3 weeks thereafter until participant is discontinued) in combination with pembrolizumab at its labelled dose and schedule. As of 05 October 2018, the dose and schedule for Part 1 Dose Expansion Phase was selected based on all available safety, efficacy and pharmacodynamic data from the Part 1 Dose Escalation Phase. Participants who were enrolled prior to 05 October 2018 to receive CMP-001 doses less than (\<) 10 mg will have the option to receive CMP-001 doses up to 10 mg on Schedule A in combination with pembrolizumab.

Drug: CMP-001; Drug: Pembrolizumab

Part 2: CMP-001 Monotherapy and Crossover to Combination

EXPERIMENTAL

Participants will receive CMP-001 10 mg via intratumoral injection by Schedule A (once weekly for 7 weeks, followed by every 3 weeks thereafter until participant is discontinued). Participants who were enrolled prior to 05 October 2018 to receive CMP-001 doses \<10 mg will have the option to receive CMP-001 doses up to 10 mg on Schedule A. Participants with documented progression while on CMP-001 monotherapy treatment will have the option to crossover to the combination treatment of CMP-001 10 mg plus pembrolizumab, at the discretion of the Investigator.

Drug: CMP-001; Drug: Pembrolizumab

Interventions

CMP-001 DRUG

CMP-001 will be administered as per the dose and schedule specified in the respective arms.

Also known as: vidutolimod

Part 1: Dose-Escalation - CMP-001 and Pembrolizumab; Part 1: Dose-Expansion - CMP-001 and Pembrolizumab; Part 2: CMP-001 Monotherapy and Crossover to Combination

Pembrolizumab DRUG

Pembrolizumab will be administered as per the schedule specified in the respective arms.

Also known as: Keytruda

Part 1: Dose-Escalation - CMP-001 and Pembrolizumab; Part 1: Dose-Expansion - CMP-001 and Pembrolizumab; Part 2: CMP-001 Monotherapy and Crossover to Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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
• 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 may not qualify if:

• 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
• 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
• 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.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (13)

Banner MD Anderson Cancer Center

Phoenix, Arizona, 85006, United States

Location

University of Arizona

Tucson, Arizona, 85721, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Georgetown

Washington D.C., District of Columbia, 02007, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: February 11, 2016
• Study Start: April 12, 2016
• Primary Completion: December 6, 2022
• Study Completion: December 6, 2022
• Last Updated: July 4, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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

Locations

US (13)