A Study Investigating the Safety and Tolerability of an Immune Treatment in Cancer Patients With Lesions to the Skin

NCT04059588 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: DKN-0993
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and tolerability of 2141-V11 in people who have cancer that does not respond to standard treatment and who have skin lesions (skin tumors) associated with their cancer. The study will also test how the body processes and responds to 2141-V11, and if the study drug has cancer fighting activity in people. The study drug activates a naturally occurring protein called CD40. By activating CD40, cells of the immune system are better able to identify and kill cancer cells. We are testing if injection of 2141-V11 into metastasis to the skin will be safe and well tolerated, and may result in immune activation in patients with solid tumors that have metastasis to the skin.

Conditions

Cancer; Solid Tumor; Cancer of Skin

Keywords

Solid Tumors; Skin lesions; Immunotherapy; CD40 antibody; Cancer; intratumoral; intralesional; metastases; metastasis

Outcome Measures

Primary Outcomes (4)

• Number of patients with treatment-emergent adverse events assessed by NCI CTCAE v4.03

  Adverse events

  through study completion, an average of 2 years

• Incidence and severity of DLTs reported and their relationship to 2141-V11 administration assessed by NCI CTCAE v4.03

  Dose limiting toxities

  through study completion, an average of 2 years

• Change from baseline laboratory assessments and toxicities over time in abnormal Complete Blood Count labs and Complete Metabolic Panel labs assessed by SI laboratory reference ranges

  Change from baseline laboratory assessments and toxisities over time

  through study completion, an average of 2 years

• Changes from baseline in anti-drug antibody (ADA) responses to 2141-V11 exposure over time

  Anti-Drug antidoby (ADA) response over time

  through study completion, an average of 2 years

Study Arms (1)

Injection of 2141-V11

EXPERIMENTAL

Open label study drug 2141-V11 at escalating doses until MTD is determined, and expansion utilizing the MTD.

Drug: 2141 V-11

Interventions

2141 V-11 DRUG

intratumoral injection of 2141-V11

Injection of 2141-V11

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years old
• Must have measurable or evaluable metastatic disease (at least more than 1 lesion) as evidenced by physical exam or imaging
• Must have an identifiable metastatic lesion of the skin, subcutaneous tissue, or lymph node amenable to intratumoral injection. This includes all solid tumors as well as metastatic melanoma and/or melanoma with in-transit metastases.
• ECOG performance status \< 1
• Histologically confirmed diagnosis of refractory or relapsed metastatic disease
• Required values for screening laboratory tests:
• Absolute neutrophil count (ANC) \> 1000/mm3 independent of growth factor support
• Platelets \> 75,000/mm3
• Hemoglobin \> 8 g/dl
• Creatinine clearance \> 40 ml/min for the dose-escalation phase, \>25 ml/min in dose expansion phase (if safety data from dose escalation indicate this is possible)
• AST/ALT \< 3 x ULN
• Bilirubin \< 1.5 x ULN (except for participants with Gilbert's Syndrome or of non-hepatic origin)
• Patients must have refractory or relapsed disease and have must have exhausted all standard-of-care therapy for their disease
• Must be at least 4 weeks since treatment with checkpoint inhibitors or other antibody-based therapy or investigational agents
• Must be at least 2 weeks since chemotherapy, targeted small molecule therapy, cytokine therapy, or radiation therapy, and be recovered from any clinically significant toxicity experienced during treatment.

You may not qualify if:

• Concurrent anticancer therapy including investigational agents. This includes topical therapeutic agents.
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest CT scan.
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen (HBsAg) test at screening.
• Patients with past/resolved hepatitis B virus (HBV) infection (defined as having a negative HBsAg and a positive antibody to hepatitis B core antigen antibody test) are eligible only if polymerase chain reaction is negative for HBV RNA. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Has spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \> 2 weeks prior to screening.
• Vaccinated with live, attenuated viral vaccines within 4 weeks of enrollment.
• Known history of human immunodeficiency virus (HIV) or any uncontrolled active systemic infection.
• Major surgery or a wound that has not fully healed within 4 weeks of enrollment.
• Treatment with an immunosuppressive regimen of corticosteroids or other immunosuppressive medication (e.g., methotrexate, rapamycin) within 30 days of study treatment. Note: patients with adrenal insufficiency may take up to 5 mg of prednisone or equivalent daily. Topical and inhaled corticosteroids in standard doses are allowed.
• Severe infections within 4 weeks prior to Cycle 1, Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Signs and symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
• Any investigational therapy within 28 days prior to initiation of study treatment. This includes topical or injected agents.
• Significant cardiovascular disease (i.e., NYHA class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias.

Sponsors & Collaborators

• Rockefeller University: lead

Study Sites (1)

Rockefeller University

New York, New York, 10065, United States

Location

Related Publications (1)

• Osorio JC, Knorr DA, Weitzenfeld P, Yao N, Baez M, DiLillo M, Rahman J, Bromberg J, Postow MA, Ariyan C, Robson ME, Ravetch JV. Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer. Res Sq [Preprint]. 2024 Jun 3:rs.3.rs-4244833. doi: 10.21203/rs.3.rs-4244833/v1.

  PMID: 38883779 DERIVED

MeSH Terms

Conditions

Neoplasms; Skin Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Juan Osorio, MD, PhD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of 2141-V 11 using a standard 3+3 dose-escalation design.

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 16, 2019
• Study Start: January 16, 2020
• Primary Completion: March 13, 2023
• Study Completion: March 13, 2023
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)