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

NCT04059588

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Investigating the Safety and Tolerability of an Immune Treatment in Cancer Patients With Lesions to the Skin
  • Official Title: A Phase I, Dose-escalation Study Investigating the Safety and Tolerability of Intratumoral Injection of an Fc-engineered Anti-CD40 Monoclonal Antibody (2141-V11) in Patients With Cancer

Clinical Trial IDs

  • ORG STUDY ID: DKN-0993
  • NCT ID: NCT04059588

Conditions

  • Cancer
  • Solid Tumor
  • Cancer of Skin

Interventions

DrugSynonymsArms
2141 V-11Injection of 2141-V11

Purpose

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.

Detailed Description

      This is a Phase 1 open label, dose-escalation study evaluating the safety, pharmacokinetics,
      pharmacodynamics, immunogenicity, and efficacy of the Fc-engineered variant 2141-V11 in
      patients with previously treated relapsed or refractory solid tumors and locally advanced or
      metastatic solid tumors to the skin amenable to intratumoral injection.

      There are two parts to the study: a dose-finding stage (Part I), and a dose expansion stage
      (Part II). Both Part I and Part II of the study will include patients with locally advanced
      or metastatic cancers of the skin which are not amenable to standard treatment.

      A traditional 3 + 3 dose escalation design will be used (Part I). Successive cohorts of
      participants (3 participants/cohort) will be started on a fixed dose intratumoral injection
      of 2141V11 at the dose assigned to their cohort. The study drug, 2141-V11, will be dosed once
      every 3 weeks. The study drug is administered in cycles.

      The first group of study participants in Part I will receive the lowest dose of study drug.
      The next group of study participants will receive the next higher dose. This dosing scheme
      continues until the maximum tolerated dose is determined. The maximum tolerated dose (MTD)
      will be defined as 1 dose level below the dose in which DLTs are observed in >33% of the
      participants.

      Participants in Part II of the study will receive the MTD determined from Part 1 (dose
      escalation) of the study. Part II participants in the study will also receive two
      vaccinations (KLH and tetanus) to allow monitoring of their immune function.

      Participants in both Part I and II can continue to receive cycles of study drug at their
      assigned dose if they do not experience progression of disease, a serious adverse event, and
      the study is ongoing.
    

Trial Arms

NameTypeDescriptionInterventions
Injection of 2141-V11ExperimentalOpen label study drug 2141-V11 at escalating doses until MTD is determined, and expansion utilizing the MTD.
  • 2141 V-11

Eligibility Criteria

        Inclusion Criteria:

          1. Age > 18 years old

          2. Must have measurable or evaluable metastatic disease (at least more than 1 lesion) as
             evidenced by physical exam or imaging

          3. Must have an identifiable metastatic lesion of the skin or subcutaneous tissue
             amenable to intratumoral injection. This includes all solid tumors as well as
             metastatic melanoma and/or melanoma with in-transit metastases.

          4. ECOG performance status < 1

          5. Histologically confirmed diagnosis of refractory or relapsed metastatic disease

          6. Must have the ability to comply with the collection of tumor and skin biopsies, and
             tumors must be accessible for biopsy.

          7. Required values for screening laboratory tests:

               1. Absolute neutrophil count (ANC) > 1000/mm3 independent of growth factor support

               2. Platelets > 75,000/mm3

               3. Hemoglobin > 8 g/dl

               4. 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)

               5. AST/ALT < 3 x ULN

               6. Bilirubin < 1.5 x ULN (except for participants with Gilbert's Syndrome or of
                  non-hepatic origin)

          8. Patients must have refractory or relapsed disease and have must have exhausted all
             standard-of-care therapy for their disease

          9. Must be at least 4 weeks since treatment with standard or investigational
             chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, and recovered
             from any clinically significant toxicity experienced during treatment.

         10. If sexually active male or female and participating in sexual activity that could lead
             to pregnancy, agrees to use two effective methods of contraception (i.e. condom with
             spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based
             contraceptive with condom). For females, these restrictions apply for 1 month after
             the last dose of study drug. For males, these restrictions apply for 3 months after
             the last dose of study drug. Men must agree not to donate sperm during and after the
             study g. Female study participants of reproductive potential are defined as
             pre-menopausal women who have not had a sterilization procedure (e.g. hysterectomy,
             bilateral oophorectomy, tubal ligation or salpingectomy). Women are considered
             menopausal if they have not had a menses for at least 12 months and have a FSH of
             greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for
             24 consecutive months.

         11. Women of childbearing potential must have a negative beta-human chorionic gonadotropin
             (hCG) pregnancy test at screening, as well as a negative pregnancy test prior to each
             treatment

         12. Life expectancy greater than 16 weeks (should be evaluated by a prognostic score,
             e.g., Roya Marsden score)

         13. Able to comply with the treatment schedule as determined by the participant and the
             licensed practitioner

        Exclusion Criteria:

          1. Concurrent anticancer therapy including investigational agents. This includes topical
             therapeutic agents

          2. 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

          3. History of radiation pneumonitis in the radiation field (fibrosis) is permitted

          4. Patients with active hepatitis B (defined as having a positive hepatitis B surface
             antigen (HBsAg) test at screening

          5. 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.

          6. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

          7. Increased corrected QT (QTc) interval (QTc > 470 ms), patients with baseline resting
             bradycardia < 45 bpm, or baseline resting tachycardia > 100 bpm

          8. 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

          9. Vaccinated with live, attenuated viral vaccines within 4 weeks of enrollment

         10. Known history of human immunodeficiency virus (HIV) or any uncontrolled active
             systemic infection

         11. Major surgery or a wound that has not fully healed within 4 weeks of enrollment.

         12. 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

         13. 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.

         14. Signs and symptoms of infection within 2 weeks prior to Cycle 1, Day 1

         15. Any investigational therapy within 28 days prior to initiation of study treatment.
             This includes topical or injected agents

         16. 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

         17. Autoimmune disease including systemic lupus erythematosus, rheumatoid arthritis,
             multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, history of
             uveitis or other autoimmune disease if clinically significant

         18. Untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI)
             evaluation during screening or prior radiographic assessments. Patients with
             radiographically stable, asymptomatic previously irradiated lesions are eligible
             provided patient is > 4 weeks beyond completion of cranial irradiation and > 3 weeks
             of corticosteroid therapy.

         19. Known history of leptomeningeal leptomeningeal disease, patients with metastases to
             the brain stem, midbrain, pons, or medulla, and patients with metastases with 10 mm of
             the optic apparatus (optic nerve and chiasm) will be excluded from the study

         20. Requires anticoagulation with warfarin or equivalent vitamin K antagonists

         21. Has had a pulmonary embolism or any other thromboembolic event within 6 months prior
             to study entry

         22. Any approved anti-cancer therapy, including chemotherapy, immunotherapy or hormonal
             therapy, within 4 weeks prior to initiation of study treatment, with the following
             exceptions:

               1. Hormone-replacement therapy or oral contraceptives

               2. Tyrosine kinase inhibitors (TKIs) that have been discontinued > 7 days prior to
                  Cycle 1, Day 1; screening scans must be obtained after discontinuation of prior
                  TKIs

         23. Prior toxicities from previous cancer therapy, including checkpoint inhibition, that
             have not regressed to Grade < 1 severity (NCI CTCAE v4.03, or later versions) within
             28 days before Cycle 1, Day 1, with the exception of alopecia

         24. Active hepatitis C are excluded. Patients positive for hepatitis C virus (HCV)
             antibody are eligible only if polymerase chain reaction is negative for HCV RNA

         25. Any surgical procedure within less than 14 days of the first receipt of study drug.
             Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of the
             need for a major surgical procedure during the study other than for diagnosis.

         26. Pregnant or breast feeding

         27. Active infection or with a fever >38.5 degrees C within 3 days prior to the first
             scheduled treatment

         28. Any medical history, including laboratory results, deemed by the investigator to be
             likely to interfere with their participation in the study, or to interfere with the
             interpretation of the results, or any social condition that, in the opinion of the
             Investigator, might pose additional risk to the participant or confound the results of
             the study.

             -
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with treatment-emergent adverse events assessed by NCI CTCAE v4.03
Time Frame:through study completion, an average of 2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rockefeller University

Trial Keywords

  • Solid Tumors
  • Skin lesions
  • Immunotherapy
  • CD40 antibody
  • Cancer
  • intratumoral
  • intralesional

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