Clinical Trials /

SCIB1 in Melanoma Patients Receiving Pembrolizumab SCIB1-002

NCT04079166

Description:

The purpose of this study is to find out if a new treatment called SCIB1 can be used safely when added to pembrolizumab (Keytruda), a standard treatment already approved in the UK and the USA for the treatment of advanced melanoma (skin cancer). Pembrolizumab is an antibody treatment for cancer. The study will also look to see if SCIB1 can increase the likelihood that melanoma patients will respond to pembrolizumab, and also if SCIB1 can help to make those responses last longer. Pembrolizumab is considered a standard treatment for patients with advanced melanoma. SCIB1 is considered experimental. SCIB1 has been given to melanoma patients in an earlier study. It was generally well tolerated, and researchers saw some signs that it may help to stimulate the immune system, which is a way in which the body can fight the cancer. This study is expected to enrol approximately 25 melanoma patients from the UK.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: SCIB1 in Melanoma Patients Receiving Pembrolizumab SCIB1-002
  • Official Title: A Phase 2, Multicenter, Open-Label Study of SCIB1 in Patients With Advanced Unresectable Melanoma Receiving Pembrolizumab

Clinical Trial IDs

  • ORG STUDY ID: SCIB1-002
  • NCT ID: NCT04079166

Conditions

  • Malignant Melanoma

Interventions

DrugSynonymsArms
SCIB1 administered with a small, hand-held electroporation device (TDS-IM v2.0).SCIB1

Purpose

The purpose of this study is to find out if a new treatment called SCIB1 can be used safely when added to pembrolizumab (Keytruda), a standard treatment already approved in the UK and the USA for the treatment of advanced melanoma (skin cancer). Pembrolizumab is an antibody treatment for cancer. The study will also look to see if SCIB1 can increase the likelihood that melanoma patients will respond to pembrolizumab, and also if SCIB1 can help to make those responses last longer. Pembrolizumab is considered a standard treatment for patients with advanced melanoma. SCIB1 is considered experimental. SCIB1 has been given to melanoma patients in an earlier study. It was generally well tolerated, and researchers saw some signs that it may help to stimulate the immune system, which is a way in which the body can fight the cancer. This study is expected to enrol approximately 25 melanoma patients from the UK.

Detailed Description

      This is an open label, single arm Phase 2 study to determine the safety and tolerability of
      SCIB1 administered to patients with advanced melanoma using an electroporation device (the
      TDS-IM v2.0 device) when added to pembrolizumab (Keytruda), a standard treatment already
      approved for the treatment of advanced melanoma.

      The plan for this research study is for SCIB1 to be given for up to 2 years, in combination
      with pembrolizumab according to the current label.

      After receiving the first dose of SCIB1, the patient will then receive SCIB1 3 times, 3 weeks
      apart, then once 6 weeks later, and after that once every 12 weeks until the treatment is
      stopped.

      Pembrolizumab will be given by an injection into the patient's vein once every 3 weeks. The
      injection, known as an infusion, usually takes about 30 minutes to complete.

      Every time the patient has a SCIB1 infusion, they will also receive pembrolizumab.
      Additionally, there will also be some days when the patient will receive pembrolizumab alone.

      On each occasion, SCIB1 will be given by two injections into a muscle in a different limb,
      e.g. one into the upper arm and the other into the thigh. Instead of a normal needle and
      syringe, a small, hand-held device TDS-IM v2.0 will be used to inject SCIB1 into the muscles.
      The site of SCIB1 administration will alternate on each occasion.

      The injection device is designed to increase the amount of SCIB1 that is delivered to the
      muscle cells. The liquid containing SCIB1 will be delivered through the injection needle.
      Immediately after the injection, the device will give a very short electrical impulse to the
      muscle through the four thin wires at the site of the injection. The impulse will last for
      less than one tenth of a second. A short video will be shown to the patient before the first
      injection is given to show the patient what will happen.

      Before treatment starts and after consent has been given, all patients will undergo screening
      tests for up to 4 weeks to ensure the patient is eligible to take part. For screening, the
      patient will need to undergo tissue typing, a melanoma tumour biopsy will be required if an
      adequate sample for testing was not previously performed, an eye examination, blood and urine
      samples taken for clinical laboratory tests, pregnancy status (for female patients only),
      tests of their immune functions, a physical examination including their vital signs,
      performance status and an ECG, a CT scan, skin fold thickness measurement, and medical
      history collection.

      Over the 2-year treatment period, the patient will visit the hospital 14 times in the first 6
      months and then every 3 weeks when they will continue to receive treatment. The tests that
      will be carried out at each visit including blood samples taken for immunological tests,
      which are all detailed in the study information sheets given to the patient before consent is
      taken. The patients will also attend for a visit 4─6 weeks after the last treatment. Female
      participants of childbearing potential will undergo pregnancy testing at screening, before
      the first dose of SCIB1, again at week 6 prior to receiving SCIB1, prior to receiving
      subsequent doses of SCIB1 and then at the end of treatment visit.

      At all visits, all patients will have their skin lesions assessed and photographed and will
      also be asked about other medications they are taking and about any adverse effects they
      might have experienced since their previous clinic visit.

      After receiving their last dose of SCIB1 or pembrolizumab, all surviving participants will be
      followed up by telephone or during standard of care clinic visits at 3, 6, 9 and 12 months to
      be asked questions about the development of any new or recurrent cancer, development of
      infection, immunological reactions, participation in any other clinical trials and subsequent
      exposure to highly potent treatments.

      An interim clinical study report will be compiled from all study data collected up to a
      cut-off date that will be 1 year from the 1st dose of SCIB1 for the last patient enrolled.
      Data collected beyond this cut off date up to the date of the final follow up contact for the
      last patient remaining in the study will be presented in the final clinical study report.
    

Trial Arms

NameTypeDescriptionInterventions
SCIB1ExperimentalSCIB1 administered using the TDS-IM v2.0 device
  • SCIB1 administered with a small, hand-held electroporation device (TDS-IM v2.0).

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has histologically confirmed, unresectable Stage III or Stage IV melanoma as
             defined by the American Joint Committee on Cancer (AJCC) (Gershenwald et al 2017).

          -  Patient has not received prior systemic treatment for advanced disease. Prior adjuvant
             treatment, defined as treatment following resection of all detectable disease, is
             permitted; last dose must be at least 4 weeks before the first dose of SCIB1.

          -  Patient has been clinically evaluated and pembrolizumab has been determined to be an
             appropriate treatment for their advanced disease.

          -  Patient's BRAF status must be known; patients with BRAF mutation positive disease may
             be enrolled without BRAF-inhibitor treatment at the discretion of the Investigator,
             provided that they have no evidence of rapidly progressive disease (PD) (lactate
             dehydrogenase [LDH] above normal range, clinically significant tumor-related
             symptoms).

          -  Patient has at least one measurable lesion per RECIST 1.1 criteria by computed
             tomography (CT) scan or magnetic resonance imaging (MRI). Cutaneous and other
             superficial lesions are non-target lesions and are not considered measurable for the
             purposes of this protocol.

          -  Patient has an archival or fresh biopsy sample of tumor available for analysis of
             immunological markers including expression of programmed death-ligand 1 (PD-L1).

          -  Patient is HLA-A2 positive.[*]

          -  Patient is positive for HLA-DR4, HLA-DR7, HLA-DR53 or HLA-DQ6.[*]

          -  Patient is at least 18 years of age.

          -  Patient has a life expectancy of more than 3 months.

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Patient has adequate organ function as determined by protocol laboratory values.

        [*] HLA testing will be conducted at accredited laboratories by molecular (DNA) typing.

          -  Patient must be able and willing to provide written IRB/REC-approved informed consent
             prior to any study related procedure. (In the event that the patient is re-screened
             for study participation or if a protocol amendment alters the care of an ongoing
             patient, a new IRB/REC-approved ICF must be signed.)

          -  Women of child-bearing potential (including women ≤ 12 months from last menstrual
             period) must have a negative serum pregnancy test during Screening (within the 72
             hours before planned administration of the first dose of study drug on Day 1) and be
             neither breastfeeding nor intending to become pregnant during study participation, and
             shall be warned of potential fetal harm from pembrolizumab. Women of child-bearing
             potential must agree to use highly effective contraceptive methods prior to study
             entry, for the duration of study participation, and for 120 days after discontinuation
             of SCIB1 or pembrolizumab, whichever occurs last.

          -  Men who are potentially fertile with partners of childbearing potential must agree to
             use highly effective contraceptive methods for the duration of study participation and
             for 120 days after discontinuation of study treatment.

          -  Patient must be willing and able to comply with scheduled visits, treatment plan,
             laboratory tests and other study procedures.

        Exclusion Criteria:

          -  Patient has a diagnosis of uveal or ocular melanoma.

          -  Patient has active central nervous system metastases or carcinomatous meningitis
             (patients with a response to previous treatment for brain metastases are eligible
             provided that they are stable without MRI evidence of progression for at least 4 weeks
             prior to the first dose of study treatment, and systemic steroids have been withdrawn
             for at least 2 weeks).

          -  Patient has previously received a treatment to block cytotoxic T lymphocyte
             (CTL)-associated protein 4 (CTLA-4), PD-1, PD-L1, or programmed death-ligand 2 (PD-L2)
             with the following exception: patients who have received adjuvant treatment with these
             treatments are eligible.

          -  Patient is expected to require any other form of systemic or localized antineoplastic
             therapy while on study.

          -  Patient is taking any systemic steroid therapy within one week of the first dose of
             study drug or is receiving any other form of immune suppressant medication. Topical
             and inhaled steroids, such as those for the management of asthma, are permitted.

          -  Patient is receiving treatment with any investigational product within 28 days (or 5
             half-lives of the treatment concerned if longer than 28 days) prior to the first dose
             of study treatment.

          -  Patient has a previous (within 5 years) or current malignancy with the exception of
             melanoma, and curatively treated local tumors such as carcinoma-in-situ of the breast,
             cervix, basal or squamous cell carcinoma of the skin, prostate cancer with Gleason
             grade < 6 and prostate specific antigen within normal range.

          -  Patient has a concurrent illness which would preclude study conduct and assessment,
             including, but not limited to uncontrolled medical conditions, uncontrolled and active
             infection (considered opportunistic, life threatening, or clinically significant),
             uncontrolled risk of bleeding, or uncontrolled diabetes mellitus, or pulmonary disease
             (including obstructive pulmonary disease, pulmonary fibrosis, and history of
             symptomatic bronchospasm), or alcoholic liver disease, or primary biliary cirrhosis.
             Caution should be used for patients with suspected or diagnosed epilepsy.

          -  Patient has any electronic stimulation device such as cardiac demand pacemaker,
             automatic implantable cardiac defibrillator, nerve stimulator or deep brain
             stimulator.

          -  Patient has a skin-fold measurement of the cutaneous and subcutaneous tissue for all
             eligible injection sites (deltoid or quadriceps muscles with intact lymph drainage)
             that is > 50 mm.

          -  Patient has New York Heart Association (NYHA) class III or IV heart disease,
             myocardial infarction within previous 6 months, a heart rate of ≤ 50 beats per minute,
             a history of significant cardiac abnormality and/or clinically significant abnormal
             baseline ECG reading, active ischemia, or any other uncontrolled cardiac condition
             such as angina pectoris, clinically significant arrhythmia requiring therapy including
             anticoagulants, uncontrolled hypertension (> 140/90 mm Hg), significant
             cerebrovascular disease, or congestive heart failure.

          -  Patient has a history of severe hypersensitivity reaction to treatment with a
             monoclonal antibody (mAb).

          -  Patient has an active autoimmune disease or a documented history of autoimmune disease
             or syndrome that requires systemic steroids or immunosuppressive agents (patients with
             vitiligo or resolved childhood asthma/atopy are an exception and are not excluded for
             these conditions). Patients that require intermittent use of bronchodilators or local
             steroid injections, and patients with hypothyroidism stable on hormone replacement,
             are not excluded from the study.

          -  Patient has received a vaccine within the 28 days prior to first dose of study
             treatment.

          -  Patient has a known history of human immunodeficiency virus (HIV) or has any positive
             test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating active acute or
             chronic infection.

          -  Patient has a known current or recent history (within the last year) of substance
             abuse including illicit drugs or alcohol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by the recording of adverse events (AEs) (Run-In Cohort: first 6 participants enrolled)
Time Frame:From enrollment through end of treatment; up to 96 weeks
Safety Issue:
Description:National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events; CTCAE v5.0.

Secondary Outcome Measures

Measure:Effect on duration of response of SCIB1 in patients receiving pembrolizumab relative to historical data for pembrolizumab alone in this patient population (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Duration of response, measured from the point of first response (complete response or partial response) to the date of disease progression (per RECIST 1.1) or death due to any cause.
Measure:ORR of SCIB1 in participants receiving pembrolizumab relative to historical data for pembrolizumab alone in this patient population, based on the modified RECIST 1.1 for immune-based therapeutics (iRECIST) (Main Study)
Time Frame:At 1 year from the first dose of SCIB1 for the last patient enrolled, and at 1 year after the last dose of SCIB1 or pembrolizumab (whichever occurs last) for each participant.
Safety Issue:
Description:ORR as determined by iRECIST criteria.
Measure:Progression Free Survival (PFS) rate for all participants at 1 year and 2 years (96 weeks) following initiation of treatment
Time Frame:At 1 year and 2 years (96 weeks) from the first dose of SCIB1 or pembrolizumab.
Safety Issue:
Description:PFS rate at 1 year and 2 years, defined as the proportion of participants who have not progressed (per RECIST 1.1), or started new anticancer therapy, or died at time points of 1 year and 2 years (96 weeks) from the first dose of SCIB1 or pembrolizumab
Measure:Overall survival (OS) rate at 1 and 2 years (96 weeks) following initiation of treatment
Time Frame:At 1 year and 2 years (96 weeks) from the first dose of SCIB1 or pembrolizumab.
Safety Issue:
Description:OS rate at 1 year, defined as the proportion of participants who remain alive 1 year after the first dose of SCIB 1 or pembrolizumab. The same assessment will be made at 2 years (96 weeks) from the first dose of study drug.
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by the recording of adverse events (AEs) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks
Safety Issue:
Description:National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events; CTCAE v5.0.
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by the recording of vital signs (temperature) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Temperature (°C).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by the recording of vital signs (pulse) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Pulse (beats per minute).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by the recording of vital signs (respiratory rate) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Respiratory rate (breaths per minute).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by the recording of vital signs (blood pressure) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Systolic and diastolic blood pressure (mm Hg).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by a physical examination of the participant (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Physical examination of eyes, neurological and cardiovascular systems, lungs, abdomen, head, neck, ears, nose, mouth, throat, thyroid, lymph nodes, extremities, and other areas with signs and symptoms of disease (binary classification: normal or clinically significant).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by serum chemistry (creatinine, bilirubin, uric acid) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Creatinine, bilirubin - total, bilirubin - direct (if clinically indicated), uric acid (μmol/L).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by serum chemistry (including blood urea nitrogen) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Blood urea nitrogen, bicarbonate (or carbon dioxide), calcium, chloride, potassium, sodium, non-fasting glucose, phosphorus, uric acid (mmol/L).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by serum chemistry (including Alanine aminotransferase) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase (international units/L).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by serum chemistry (Albumin) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Albumin, total protein (g/L).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by serum chemistry (Thyroid-stimulating hormone) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Thyroid-stimulating hormone (mIU/L).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by serum chemistry (Free thyroxine, triiodothyronine) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Free thyroxine, triiodothyronine (pmol/L). Free thyroxine, triiodothyronine (pmol/L).
Measure:Safety and tolerability of SCIB1 in participants as assessed by hematology (red blood cell count) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Red blood cell count (10⌃12/L).
Measure:Safety and tolerability of SCIB1 in participants as assessed by hematology (including hematocrit) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Hematocrit, neutrophils to leukocyte ratio, lymphocytes to leukocyte ratio, monocytes to leukocyte ratio, eosinophils to leukocyte ratio, basophils to leukocyte ratio (%).
Measure:Safety and tolerability of SCIB1 in participants as assessed by hematology (including leukocytes) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Leukocytes, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils, platelets (10⌃9/L).
Measure:Safety and tolerability of SCIB1 in participants as assessed by hematology (corpuscular volume) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Mean corpuscular volume (fL).
Measure:Safety and tolerability of SCIB1 in participants as assessed by hematology (corpuscular hemoglobin) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Mean corpuscular hemoglobin (pg).
Measure:Safety and tolerability of SCIB1 in participants as assessed by hematology (haemoglobin, corpuscular hemoglobin) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Hemoglobin, mean corpuscular hemoglobin concentration (g/L).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by urinalysis (protein, glucose) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Protein, glucose (negative/trace/1+/2+/3+/4+).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by urinalysis (ketones, hemoglobin) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Ketones, hemoglobin (negative/trace/1+/2+/3+).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by urinalysis (pH) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:pH (pH units).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by urinalysis (specific gravity) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Specific gravity.
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by urinalysis (white blood cells, red blood cells) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:If clinically indicated: white blood cells and red blood cells (cells per high power field).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by urinalysis (bacteria, casts and crystals) (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:If clinically indicated: microscopic examination for bacteria, casts and crystals (binary classification: positive or negative).
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by 12-lead electrocardiogram (Main Study)
Time Frame:At 6 weeks after the first dose of SCIB1 or pembrolizumab, and at end of treatment (28 days after the final dose of study drug).
Safety Issue:
Description:Evaluation of standard components of the 12-lead ECG. Information regarding standard components of the ECG will not be collected systematically; however, in cases where an ECG abnormality is identified, the abnormality will be reported as an AE, and all details of the identified abnormality will be provided.
Measure:Safety and tolerability of SCIB1 in participants as assessed by performance status (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Grading of performance status as defined by the European Cooperative Group (ECOG) Performance Status score on a 6-point scale, where 0 = 'fully active, able to carry on all pre-disease performance without restriction' and 5 = 'dead'.
Measure:Safety and tolerability of SCIB1 in participants receiving pembrolizumab as assessed by the injection site reaction (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Clinician assessment of the injection site reaction using a 3-point scale where 1 = 'mild' and 3 = 'severe'.
Measure:Tolerability of SCIB1 in participants as assessed by a tolerability questionnaire (Main Study)
Time Frame:From enrollment through end of treatment; up to 96 weeks.
Safety Issue:
Description:Patient assessment of the tolerability of the injection using a 5-point scale where 1 = 'no sensation' and 5 = 'extreme pain'.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Scancell Ltd

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