Phase 1B Study Evaluating Alternative Routes of Administration of CMP-001 in Combination With Pembrolizumab in Participants With Advanced Melanoma

NCT03084640 | Completed Phase 1 FDA Drug

• 1 other identifier: CMP-001-002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

CMP-001-002 is a Phase 1b study of CMP-001 administered to participants with advanced melanoma who are either receiving pembrolizumab, or who have previously received an anti-programmed cell death protein 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy for advanced melanoma, and who have not responded (that is, immunotherapy resistant). This study will be conducted in two parts: Part 1 will consist of a Dose Escalation Phase and a Dose Expansion Phase

• Dose Escalation Phase will be conducted to assess and identify a recommended phase 2 dose (RP2D) of CMP-001 for subcutaneous (SC) administration
• The Dose Expansion Phase is intended to further characterize the safety, pharmacodynamics, and preliminary evidence of antitumor activity of the RP2D of CMP-001 administered SC in combination with pembrolizumab Part 2 will assess the safety and preliminary evidence of antitumor activity of CMP-001, administered both SC and intratumoral (IT) when given in combination with pembrolizumab. Participants will continue treatment with CMP-001 in combination with pembrolizumab as long as they do not experience unacceptable toxicities and when continued treatment, is in the participant's best interest according to the Investigator.

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (2)

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

  15 days from date of first CMP-001 injection (Week 1 Day 1)

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

  TEAEs will be evaluated 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 2.5 years)

Secondary Outcomes (13)

• 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 2.5 years)

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

  From screening up to end of treatment (EOT) (up to approximately 2.5 years)

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

  From screening up to EOT (up to approximately 2.5 years)

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

  From screening up to EOT (up to approximately 2.5 years)

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

  From screening up to EOT (up to approximately 2.5 years)

Study Arms (3)

Part 1: Dose-Escalation - CMP-001 (SC) and Pembrolizumab

EXPERIMENTAL

Participants will receive up to 7 escalating dose levels (5 milligrams \[mg\], 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, and 20 mg) of CMP-001 via SC injection once a week for 3 weeks and every 3 weeks thereafter until discontinuation of treatment in combination with pembrolizumab at its labelled dose and schedule.

Drug: CMP-001; Drug: Pembrolizumab

Part 1: Dose-Expansion - CMP-001 (SC) and Pembrolizumab

EXPERIMENTAL

Participants will receive RP2D (as determined in Part 1 dose-escalation phase) of CMP-001 via SC injection once a week for 3 weeks and every 3 weeks thereafter until discontinuation of treatment in combination with pembrolizumab at its labelled dose and schedule.

Drug: CMP-001; Drug: Pembrolizumab

Part 2: CMP-001 (SC and IT) and Pembrolizumab

EXPERIMENTAL

Participants will receive CMP-001 via SC injection once weekly for 2 weeks, then IT injection once weekly for 4 weeks, and SC injection once weekly for every 3 weeks thereafter until discontinuation of treatment in combination with pembrolizumab at its labelled dose and schedule. CMP-001 planned IT dose level in Part 2 will be up to 10 mg and the SC dose will be the RP2D determined from Part 1 dose-escalation phase of the study.

Drug: CMP-001; Drug: Pembrolizumab

Interventions

CMP-001 DRUG

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

Part 1: Dose-Escalation - CMP-001 (SC) and Pembrolizumab; Part 1: Dose-Expansion - CMP-001 (SC) and Pembrolizumab; Part 2: CMP-001 (SC and IT) and Pembrolizumab

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 (SC) and Pembrolizumab; Part 1: Dose-Expansion - CMP-001 (SC) and Pembrolizumab; Part 2: CMP-001 (SC and IT) and Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Participants enrolled into Part 1 must have tumor lesions where repeated IT injections are not feasible and in whom, based on the Investigator's judgement, SC injection is the only viable route of CMP-001 administration. Participants with lesions that are easily accessible for IT injections are not eligible to participate in Part 1. Participants enrolled into Part 2 must have at least one tumor lesion with a longest diameter of \>/= 0.5 cm amenable for IT injection of CMP-001.
• Histopathologically confirmed diagnosis of metastatic or unresectable malignant melanoma. Ocular melanoma participants are not eligible.
• Participants must have received prior treatment with anti-PD-1 or anti-PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and had documented progression per RECIST. Participants must have received at least 4 doses of anti-PD-1 or anti-PD-L1 therapy.
• 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) meet the following standards:
• Bone marrow function: neutrophil count greater than or equal to (\>/=) 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) of each institution, aspartate aminotransferase and alanine aminotransferase \<=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.

You may not qualify if:

• Pregnant or breast feeding
• 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. However, if an investigational drug has a short half-life, a reduced wash out period may be acceptable upon permission given by the Sponsor.
• Received treatment with anti- cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody within 30 days prior to the start of CMP-001 dosing on Week 1 Day 1.
• Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Developed autoimmune disorders of Grade 4 while on prior immunotherapy. 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 greater than (\>) 10 milligrams per day (mg/day) for at least 2 weeks.
• Require systemic pharmacologic doses of corticosteroids at or above 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 systemic steroids 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 (that is, symptomatic or growing) central nervous system (CNS) metastases. Participants with CNS metastases are eligible for the trial if: a) the metastases have been treated by surgery and/or radiotherapy; b) the participant is off corticosteroids \>10 mg/day and is neurologically stable for at least 2 weeks prior to Screening; c) brain MRI completed within 3 months of Screening.
• 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 that is, 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.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (4)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Pittsburgh Medical Center - Cancer Center

Pittsburgh, Pennsylvania, 15232, 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 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: March 6, 2017
• First Posted: March 21, 2017
• Study Start: May 4, 2017
• Primary Completion: July 2, 2021
• Study Completion: September 30, 2021
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

US (4)