Study Stopped
The study was canceled for administrative reasons.
Intratumoral Cavrotolimod Combined With Pembrolizumab or Cemiplimab in Patients With Merkel Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, or Other Advanced Solid Tumors
Merkel Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, or Other Advanced Solid Tumors: A Phase 1b/2 Study of Cavrotolimod Combined With Pembrolizumab or Cemiplimab
1 other identifier
interventional
57
1 country
26
Brief Summary
This is a phase 1b/2, open-label, two-part, multicenter trial designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of intratumoral cavrotolimod injections alone and in combination with intravenous pembrolizumab or cemiplimab in patients with Merkel Cell Carcinoma, cutaneous squamous cell carcinoma, and advanced solid tumors. Phase 1b of this trial is a 3+3 dose escalation study evaluating escalating or intermediate dose levels of cavrotolimod given with a fixed dose of pembrolizumab. The Phase 2 dose expansion part of the study will consist of two primary cohorts of patients: Merkel cell carcinoma and cutaneous squamous cell carcinoma. Patients in the Merkel Cell Carcinoma cohort will receive IT cavrotolimod combined with a fixed, standard dose of pembrolizumab while the Cutaneous Squamous Cell Carcinoma cohort will receive IT cavrotolimod combined with a fixed, standard dose of cemiplimab. The Phase 2 dose expansion is designed to provide a preliminary estimate of efficacy in patients that have progressed on an anti-PD-(L)1 CPI.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Dec 2018
Typical duration for phase_1
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 19, 2018
CompletedFirst Posted
Study publicly available on registry
September 26, 2018
CompletedStudy Start
First participant enrolled
December 13, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 30, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 30, 2022
CompletedApril 7, 2022
March 1, 2022
3.3 years
September 19, 2018
March 30, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Adverse events of cavrotolimod alone and in combination with pembrolizumab or cemiplimab
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Study day 36
Secondary Outcomes (4)
Recommended Phase 2 dose
12 months
Objective response rate (ORR) per RECIST v1.1
24 months
Measure changes in correlative biomarkers including tumor-infiltrating lymphocytes, PD-L1 and other checkpoint expression at baseline, after cavrotolimod monotherapy, and after combination therapy of both cavrotolimod and pembrolizumab or cemiplimab.
Study day 36
Measure changes in gene expression profiles at baseline, after cavrotolimod monotherapy, and after combination therapy of both cavrotolimod and pembrolizumab or cemiplimab.
Study day 36
Study Arms (7)
Dose Escalation Phase 1b
EXPERIMENTALDetermine the recommended Phase 2 dose of cavrotolimod in combination with pembrolizumab.
Dose Expansion Phase 2; Merkel cell carcinoma
EXPERIMENTALDetermine the safety and preliminary efficacy of cavrotolimod and pembrolizumab in patients with advanced Merkel cell carcinoma that have progressed on an anti-PD-1 / anti-PD-L1 therapy.
Dose Expansion Phase 2, cutaneous squamous cell carcinoma
EXPERIMENTALDetermine the safety and preliminary efficacy of cavrotolimod and cemiplimab in patients with advanced cutaneous squamous cell carcinoma that have progressed on an anti-PD-1.
Exploratory Phase 2, Merkel cell carinoma
EXPERIMENTALDetermine the safety and preliminary efficacy of cavrotolimod and pembrolizumab in patients with advanced Merkel cell carcinoma that have progressed on anti-PD-1 / anti-PD-L1 therapy.
Exploratory Phase 2, Subcutaneous Dosing Cohort
EXPERIMENTALDetermine the safety and preliminary efficacy of cavrotolimod and pembrolizumab in patients with no cutaneous, subcutaneous, or accessible nodal tumor lesions amenable that have progressed on anti-PD-1 / anti-PD-L1 therapy.
Exploratory Phase 2, Melanoma
EXPERIMENTALDetermine the safety and preliminary efficacy of cavrotolimod and pembrolizumab in patients with locally Advanced or Metastatic Melanoma that have progressed on anti-PD-1 / anti-PD-L1 therapy.
Exploratory Phase 2, Liver Lesion
EXPERIMENTALDetermine the safety and preliminary efficacy of cavrotolimod and pembrolizumab in patients with metastatic solid tumors with liver metastases that have progressed on anti-PD-1 / anti-PD-L1 therapy.
Interventions
Intratumorally dosed cavrotolimod.
Pembrolizumab dosing as per the US prescribing information.
Cemiplimab dosing as per the US prescribing information.
Eligibility Criteria
You may qualify if:
- Written informed consent.
- Male or female ≥18 years of age.
- Must have an advanced inoperable histologically diagnosed solid tumor.
- Phase 2 Merkel Cell Carcinoma Dose Expansion Cohort: locally advanced or metastatic Merkel cell caricinoma
- Phase 2 Cutaneous Squamous Cell Carcinoma Dose Expansion Cohort: locally advanced or metastatic cutaneous squamous cell carcinoma
- Phase 2 Merkel Cell Carcinoma Exploratory Expansion Cohort: locally advanced or metastatic Merkel cell carcinoma
- Phase 2 Melanoma Exploratory Expansion Cohort: Locally advanced or metastatic melanoma
- Phase 2 Subcutaneous Dosing Exploratory Cohort: Locally advanced or metastatic solid tumors
- Phase 2 Liver Lesion Exploratory Cohort: metastatic solid tumors with liver metastases
- Phase 1b, Phase 2 Merkel Cell Carcinoma Dose Expansion Cohort, Phase 2 Cutaneous Squamous Cell Carcinoma Dose Expansion Cohort, Phase 2 Merkel Cell Carcinoma Exploratory Expansion Cohort, Phase 2 Melanoma Exploratory Expansion Cohort:
- At least one tumor lesion amenable to repeated IT injection via palpation or ultrasound. Injection of deep visceral lesions is not permitted.
- Patients enrolled in subcutaneous dosing cohort do not need lesions amenable to subcutaneous dosing.
- Phase 1b and Phase 2 Melanoma Exploratory Expansion Cohort:
- Agrees to provide a newly obtained biopsy of one or two lesions, and agrees to repeat biopsies, if applicable.
- Phase 1b:
- +30 more criteria
You may not qualify if:
- Small molecule or tyrosine kinase inhibitor within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of cavrotolimod, chemotherapy or biological cancer therapy within 3 weeks prior to the first dose of cavrotolimod, nitrosourea, or radioisotope within 6 weeks prior to first dose of cavrotolimod, or non-recovery to CTCAE G1 or better from the AEs due to cancer therapeutics administered more than 4 weeks earlier.
- Known hypersensitivity to any phosphorothioate oligonucleotide, or previous exposure to a TLR9 agonist drug.
- Previous severe hypersensitivity reaction to treatment with pembrolizumab, cemiplimab or another anti-PD-(L)1 monoclonal antibody.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) \>1.
- Symptomatic ascites or pleural effusion. A patient with these conditions who has received treatment such as therapeutic thoracentesis or paracentesis and is clinically stable, defined as not requiring repeat drainage procedure within 2 weeks, may be considered after discussion with the Medical Monitor.
- Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to the first dose of cavrotolimod, have no evidence of new or enlarging brain metastases and are off steroids for at least 14 days prior to the first dose of cavrotolimod.
- Known history of a hematologic malignancy, malignant primary brain tumor or malignant sarcoma, or of another malignant primary solid tumor (other than that under study), with the following exceptions: 1) patients who have undergone potentially curative therapy with no evidence of that disease for 3 years prior to the first dose of cavrotolimod; 2) patients who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers; 3) stable chronic lymphocytic leukemia not requiring treatment within 3 years prior to the first dose of cavrotolimod.
- Use of systemic corticosteroids to treat inflammatory or autoimmune symptoms within 15 days or other immunosuppressive drugs within 30 days prior to the first dose of cavrotolimod. Inhaled and topical corticosteroids are permitted. Up to 10 mg/day prednisone or equivalent is permitted for hypothyroidism or adrenal insufficiency.
- Received an investigational product or been treated with an investigational device within 30 days prior to the first dose of cavrotolimod or will start any other investigational product or device study within 30 days after last study drug administration.
- History or clinical evidence of any surgical or medical condition which the Investigator judges as likely to interfere with the results of the study or pose an additional risk in participating e.g., rapidly progressive or uncontrolled disease involving a major organ system-vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine or an immunodeficiency, or clinically significant active psychiatric or abuse disorders.
- Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study through 4 months after the last dose of cavrotolimod, pembrolizumab, or cemiplimab.
- Allergy or intolerance preventing use of H1 blockers (e.g., diphenhydramine, cetirizine) and H2 blockers (e.g., famotidine) used as antihistamine premedication prior to cavrotolimod injection.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Exicure, Inc.lead
Study Sites (26)
University of Arizona Cancer Center
Tucson, Arizona, 85719, United States
University of California Irvine
Orange, California, 92868, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94185, United States
John Wayne Cancer Institute / Providence St. John's Health Center
Santa Monica, California, 90401, United States
University of Colorado Cancer Center
Aurora, Colorado, 80045, United States
Western States Cancer Center
Englewood, Colorado, 80113, United States
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611, United States
Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
Norton Cancer Center
Louisville, Kentucky, 40241, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University St. Louis
St Louis, Missouri, 63110, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Valley - Mount Sinai Comprehensive Cancer Center
Paramus, New Jersey, 07652, United States
Perlmutter Cancer Center
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Duke Cancer Institute
Durham, North Carolina, 27710, United States
University of Cincinnati
Cincinnati, Ohio, 45267, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
University of Pittsburgh Medical Center / Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Sammons Cancer Center
Dallas, Texas, 75246, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Washington- Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
West Virginia Cancer Institute
Morgantown, West Virginia, 26506, United States
Related Publications (1)
Milhem MM, Wise-Draper TM, Chandra S, Hanna GJ, Laux DE, Medina TM, Ansstas G, Daud A, Kelly CM, O'Day SJ, Perez CA, Wong MK, Friedlander PA, Kristedja TS, Burgess MA, Cowey CL, Hanks BA, Weight RM, Daniel WL, Feltner DE, Mix S, Sindelar L, Bexon AS, Bexon MF, Michel RE, Bhatia S. Phase 1b/2 study evaluating safety, efficacy and immune effects of TLR9 agonist cavrotolimod with anti-PD-1 antibodies among patients with advanced solid tumors. J Immunother Cancer. 2025 Jul 25;13(7):e011651. doi: 10.1136/jitc-2025-011651.
PMID: 40713179DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Exicure Inc.
Exicure, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 19, 2018
First Posted
September 26, 2018
Study Start
December 13, 2018
Primary Completion
March 30, 2022
Study Completion
March 30, 2022
Last Updated
April 7, 2022
Record last verified: 2022-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Beginning 9 months and ending 36 months following article publication.
- Access Criteria
- Access will be considered to researchers who provide a methodologically sound proposal. Analysis must achieve the aims outlined in the approved proposal. Proposals should be directed to edegoma@exicuretx.com. To gain access, data requestors will need to sign a data access agreement. Data are available for 36 months following article publication.
Individual participant data that underlie the results reported in the article, after de-identification (text, tables, figures, and appendices) will be shared to researchers who provide a methodologically sound proposal and sign a data access agreement.