Safety of Intranodal ECI-006 in Melanoma Patients

NCT03394937 | Terminated Phase 1 DMC

• 1 other identifier: E011-MEL
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 9

Brief Summary

The purpose of this study is to assess the safety and tolerability of cancer immunotherapy ECI-006 and to determine its ability to induce a measurable immune response against the tumor associated antigens. In Cohort 1, ECI-006 will be administered 5 times by intranodal injection in melanoma patients after resection of their tumor. In Cohort 2, ECI-006 will be administered 9 times by intranodal injection on top of standard of care anti PD1 in metastatic melanoma patients with stable disease after 3 to 12 months treatment. ECI-006 activates key immunologically active cells to direct the immune system against the cancer. Expected potential risks for ECI-006 are non-serious and related to the local administration of the product. Hence, the therapy suggested here has the promise to offer considerable benefit to patients without any major risk.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of treatment-emergent adverse events (TEAEs), including the incidence of dose-limiting toxicities (DLTs), graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  Types of toxicities, incidences and severity will be summarized by descriptive statistics

  24 weeks

Secondary Outcomes (1)

• Immune response associated with ECI-006 administration

  24 weeks

Study Arms (4)

Cohort 1 600 µg ECI-006

EXPERIMENTAL

Patients with melanoma are planned to be dosed intranodal with up to 5 doses of 600 µg ECI-006

Biological: ECI-006

Cohort 1 1800 µg ECI-006

EXPERIMENTAL

Patients with melanoma are planned to be dosed intranodal with up to 5 doses of 1800 µg ECI-006

Biological: ECI-006

Cohort 2 1800 µg ECI-006

EXPERIMENTAL

Patients with melanoma are planned to be dosed intranodal with up to 9 doses of 1800 µg ECI-006

Biological: ECI-006

Cohort 2 3600 µg ECI-006

EXPERIMENTAL

Patients with melanoma are planned to be dosed intranodal with up to 9 doses of 3600 µg ECI-006

Biological: ECI-006

Interventions

ECI-006 BIOLOGICAL

ECI-006 consists of TriMix and 5 tumor associated antigens mRNA. TriMix is a mixture of mRNAs that encodes potent immune stimulating molecules

Cohort 1 1800 µg ECI-006; Cohort 1 600 µg ECI-006; Cohort 2 1800 µg ECI-006; Cohort 2 3600 µg ECI-006

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years and less than or equal to 80 years.
• Patients with American Joint Committee on Cancer (AJCC) Stage IIc, III or IV.
• Patients must have no evidence of disease as evidenced by a whole body 18F fluorodeoxyglucose (FDG) positron emission tomography \[PET\]/computed tomography \[CT\] scan to be done at maximum 2 weeks before Visit 2. To exclude the presence of tumor lesions in the brain magnetic resonance imaging (MRI) may be performed.
• Full recovery from all prior therapies. A maximum period of 12 weeks following major surgery, or any other major invasive procedure is allowed before start of the study medication; at least 4 weeks should be between major surgery and the start of the immunotherapy
• Female patients of childbearing potential should have a negative serum pregnancy test at Visit 1 (Screening) and should use an efficient method of birth control from screening until the first menses after a 4 week period after the last dose of study medication.

You may not qualify if:

• Patients with primary uveal or mucosal melanoma.
• Patients who have received prior systemic therapy and/or active immunotherapy for melanoma, such as antigen loaded dendritic cells or chimeric antigen receptor (CAR) T cells, are excluded. Systemic adjuvant treatment for melanoma that is more than 5 years ago and prior local treatment of primary and metastatic tumor lesions (e.g., surgical resection, isolated limb perfusion radiotherapy) are allowed.
• Patients with serious intercurrent chronic or acute illness such as pulmonary \[asthma or chronic obstructive pulmonary disease (COPD)\] or cardiac (New York Heart Association \[NYHA\] class III or IV) or hepatic disease or other illness considered by the investigator to constitute an unwarranted high risk for investigational drug treatment.
• Concurrent second malignancy other than non-melanoma skin cancer, or controlled superficial bladder cancer. In the event of prior malignancies treated surgically, the patient must be considered NED (no evidence of disease) for a minimum of 3 years prior to enrolment.
• Patients on steroid therapy \> 10 mg prednisone (or equivalent) or other immunosuppressive agents such as azathioprine or cyclosporine A (but not limited to these) are excluded on the basis of potential immune suppression. Patients must have had 8 weeks of discontinuation of any steroid therapy exceeding \> 10 mg prednisone (or equivalent) before first dose.
• Histologically confirmed AJCC Stage III or Stage IV unresectable disease.
• Patient must be free of progression and have stable disease after at least 3 months but less than 12 months of first-line immunotherapy (pembrolizumab, nivolumab or combination of nivolumab and ipilimumab). Patients with clinically stable disease can be either:
• Patients with stable disease as defined by RECIST1.1 criteria as assessed on 2 consecutive imagings, or
• Patients deemed unlikely to respond further to the standard of care immunotherapy by the investigator, after an initial partial response.
• Patient must continue with standard of care pembrolizumab or nivolumab during the study.
• Measurable disease by means of clinical examination, computed tomography (CT) or magnetic resonance imaging (MRI) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, defined as:
• At least 1 tumor lesion that can be accurately and serially measured in at least 1 dimension, and for which the greatest diameter is ≥ 10 mm or at least one malignant lymph node for which the short axis is ≥ 15 mm as measured by contrast enhanced or spiral CT scan and/or
• At least 1 superficial cutaneous melanoma lesion ≥ 10 mm as measured by calipers and/or
• At least 1 subcutaneous melanoma ≥ 10 mm lesion and/or
• Multiple superficial melanoma lesions which in aggregate have a total diameter of ≥ 10 mm

Sponsors & Collaborators

• eTheRNA immunotherapies: lead

Study Sites (9)

032-004_GZA Sint-Augustinus

Antwerp, Belgium

Location

032-002_UCL Brussels

Brussels, Belgium

Location

032-003_AZ Maria Middelares

Ghent, Belgium

Location

032-001_University Hospital Brussel

Jette, Belgium

Location

Site 032-007_AZ Sint Maarten

Mechelen, Belgium

Location

034-001_Hospital Clinic de Barcelona

Barcelona, Spain

Location

034-002_MD Anderson Cancer Center

Madrid, Spain

Location

034-003_Hospital Universitario Ramon y Cajal

Madrid, Spain

Location

034-004_Clinica Universidad de Navarra

Pamplona, Spain

Location

MeSH Terms

Conditions

Melanoma

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

Model Details: • Drug: ECI-006 mRNA Cohort 1: 5 intranodal injections of either 600 µg or 1800 µg mRNA Cohort 2: 9 intranodal injections of either 1800 µg or 3600 µg mRNA

Study Record Dates

• First Submitted: November 28, 2017
• First Posted: January 9, 2018
• Study Start: June 27, 2017
• Primary Completion: December 31, 2020
• Study Completion: January 29, 2021
• Last Updated: June 21, 2021

Record last verified: 2020-09

Locations

BE (5); ES (4)