Intratumoral Cavrotolimod Combined With Pembrolizumab or Cemiplimab in Patients With Merkel Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, or Other Advanced Solid Tumors

Stopped early · Phase 1/Phase 2

Conditions studied: Advanced or Metastatic Merkel Cell Carcinoma, Advanced or Metastatic Cutaneous Squamous Cell Carcinoma, Advanced or Metastatic Melanoma, Advanced or Metastatic Head and Neck Squamous Cell Carcinoma, Advanced or Metastatic Solid Tumors

In brief

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.

Key facts

Study ID

NCT03684785

Run by

Exicure, Inc.

People needed

57

Starts

2018-12-13

Expected to finish

2022-03-30

Last updated by the study team

2022-04-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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:
• In the investigator's opinion the patient may derive clinical benefit from the treatment or is ineligible for a particular form of standard therapy due to tolerability, or the patient failed one or more established standard medical anti-cancer therapies. Exposure to anti-PD-(L)1 or anti-CTLA-4 antibody CPIs is permitted but not required.
• Phase 2 Merkel Cell Carcinoma Dose Expansion Cohort:
• i. At least a minimum number of cycles of avelumab, nivolumab, or pembrolizumab. Prior anti-CTLA-4 antibody therapy, including as most recent preceding therapy in combination with avelumab or pembrolizumab, is permitted but not required.
• ii. Confirmed progressive disease during treatment with avelumab or pembrolizumab therapy,
• Phase 2 Cutaneous Squamous Cell Carcinoma Dose Expansion Cohort
• i. At least a minimum number of cycles of cemiplimab, nivolumab, or pembrolizumab. Prior ipilimumab therapy, including as most recent preceding therapy in combination with cemiplimab, nivolumab, or pembrolizumab, is permitted but not required.
• ii. Confirmed progressive disease on cemiplimab or pembrolizumab therapy
• Phase 2 MCC and Melanoma Exploratory Expansion Cohort and Phase 2 Subcutaneous Dosing Exploratory Expansion Cohort:
• i. Treatment duration with anti-PD-(L)1 antibody ≥8 weeks as the most recent preceding therapy prior to being enrolled in this study with confirmed progression. Anti-PD-(L)1 was administrated for metastatic or locally advanced Merkel Cell Carcinoma or melanoma. Prior ipilimumab therapy, including as most recent therapy in combination with anti-PD-(L)1 therapy, is permitted but not required.
• ii. Confirmed progressive disease on anti-PD-(L)1 antibody therapy

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.
• Significant autoimmune disease that requires or required systemic steroids or immunosuppressive agents within the last year. The following are not exclusionary: 1) vitiligo, resolved asthma/atopy, and limited eczema; 2) conidtions requiring intermittent use of bronchodilators or local steroid injections; 3) hypothyroidism or adrenal insufficiency that is stable on hormone replacement; or 4) irAEs related to checkpoint inhibitor therapy, provided inclusion criterion #10 and exclusion criterion #11 are met.
• 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.

Where it is running

• University of Arizona Cancer Center — Tucson, Arizona, United States
• University of California Irvine — Orange, California, United States
• UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, California, United States
• John Wayne Cancer Institute / Providence St. John's Health Center — Santa Monica, California, United States
• University of Colorado Cancer Center — Aurora, Colorado, United States
• Western States Cancer Center — Englewood, Colorado, United States
• Sylvester Comprehensive Cancer Center — Miami, Florida, United States
• Northwestern University Feinberg School of Medicine — Chicago, Illinois, United States
• Holden Comprehensive Cancer Center — Iowa City, Iowa, United States
• Norton Cancer Center — Louisville, Kentucky, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Washington University St. Louis — St Louis, Missouri, United States
• Dartmouth-Hitchcock Medical Center — Lebanon, New Hampshire, United States
• Valley - Mount Sinai Comprehensive Cancer Center — Paramus, New Jersey, United States
• Perlmutter Cancer Center — New York, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Duke Cancer Institute — Durham, North Carolina, United States
• University of Cincinnati — Cincinnati, Ohio, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• Oregon Health and Science University — Portland, Oregon, United States
• University of Pittsburgh Medical Center / Hillman Cancer Center — Pittsburgh, Pennsylvania, United States
• Sammons Cancer Center — Dallas, Texas, United States
• Baylor College of Medicine — Houston, Texas, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• University of Washington- Seattle Cancer Care Alliance — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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