Study to Assess the Tolerability of a Bispecific Targeted Biologic IMCgp100 in Malignant Melanoma
Condition: Malignant Melanoma
MeSH terms: Melanoma
Intervention: IMCgp100
Intervention description: For each arm, the study will be divided into two parts: In part 1, dose escalation, the MTD or RP2D for each dosing regimen will be established. In part 2, dose expansion, a cohort of participants will be treated at the RP2D or MTD.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 84.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Melanoma; Phase I; Biologic

Summary:

      IMCgp100 is a new biological therapy designed for the treatment of melanoma skin cancer. The
      drug is designed to target melanoma cells and stimulate immune cells to kill them. This trial
      is designed to establish the level of drug that can be given to a patient that is tolerable.
      It also designed to establish the best dosing schedule for the drug and to look for signals
      that the drug is working as intended.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologically documented Stage IV malignant melanoma or unresectable Stage III
             melanoma for which no standard effective therapy exists or for which an appropriate
             window exists between alternative therapeutic options. Participants for whom early
             treatment with vemurafenib is indicated, e.g. rapidly progressing or symptomatic
             disease, are excluded from this trial.

          2. Previous surgery (other than resection of skin metastases), radiotherapy,
             chemotherapy, immunotherapy or experimental therapy completed > 4 weeks before and all
             adverse events resolved to ≤ grade 1. In cases where localized radiotherapy has been
             applied, treatment with IMCgp100 can be commenced after a two week period.

          3. Human leukocyte antigen (HLA) A2 positive.

          4. ≥ 18 years old.

          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

          6. Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)
             1.1 criteria. Participants participating in the dose escalation part of Arm 2 only
             require assessable disease.

          7. Life expectancy > 3 months.

          8. Blood tests within the following parameters:

               1. Platelet count ≥ 100 x10⁹/L

               2. Hemoglobin ≥ 9g/dL (blood transfusion to achieve this level is permitted)

               3. Calculated creatinine clearance ≥ 50 mL/min using the modified Cockroft-Gault
                  equation

               4. Neutrophil count ≥1x10⁹/L

               5. Lymphocyte count ≥ 0.5x10⁹/L

          9. Female participants of childbearing potential must use maximally effective birth
             control during the period of therapy, must be willing to use contraception for 6
             months following the last study drug infusion and must have a negative urine or serum
             pregnancy test upon entry into this study. Otherwise, female participants must be
             postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.

         10. Male participants must be surgically sterile or willing to use a double barrier
             contraception method upon enrollment, during the course of the study, and for 6 months
             following the last study drug infusion.

         11. Participants with a history of adrenal insufficiency, maintained on stable replacement
             dose corticosteroid (< 10 mg/d prednisone or the equivalent) are eligible for
             treatment with IMCgp100, unless there is a past history of adrenal crisis. Eligible
             participants with a history of adrenal insufficiency receiving replacement dose
             corticosteroid must receive prophylactic stress dose corticosteroid prior to dosing
             during the first four doses of IMCgp100 treatment, regardless of weekly or daily
             dosing regimen.

         12. Able to give informed consent.

        Exclusion Criteria:

        Participants meeting any of the following criteria will be excluded from the study:

          1. Symptomatic brain metastases that are unstable, require steroids, or that have
             required radiation within the last 28 days.

          2. Other active malignancy in the past 5 years except carcinoma in situ, completely
             excised nonmelanomatous skin cancer or any other malignancy that in the opinion of the
             investigator is considered to be cured.

          3. Comorbid medical condition that would increase the risk of toxicity in the opinion of
             the investigator or sponsor. Symptomatic on-going infection must be resolved before
             the patient can be treated in the study.

          4. Uveitis.

          5. Had myocardial infarction within 1 year before enrolment, symptomatic congestive heart
             failure (New York Heart Association > Class II), unstable angina or unstable cardiac
             arrhythmia requiring medication.

          6. Has an ejection fraction < 50%.

          7. Clinically significant electrocardiogram (ECG) changes that obscure the ability to
             assess the RR, PR and QT intervals. Participants with corrected QT interval (QTc)
             calculated by Bazetts or locally preferred formula which is greater than 500 ms.

          8. Has hepatic function as follows:

               1. Aspartate aminotransferase > 2.5 x upper limit of normal (ULN)

               2. Alanine aminotransferase > 2.5 x ULN

               3. Bilirubin > 2.0 x ULN

               4. Prothrombin time or partial thromboplastin time > 1.5 x ULN

          9. Bleeding diathesis

         10. Immunosuppressive condition or treatment including previous transplantation,
             splenectomy or known human immunodeficiency virus (HIV) infection.

         11. Has a history of adult seizures.

         12. Participants with evidence of a raised intracranial pressure in Arm 2 of the study who
             will have a cerebrospinal fluid sample taken.

         13. Participants receiving chronic corticosteroid treatment (longer than 8 weeks duration)
             for management of pre-existing adverse events at any dose, or participants with a
             history of chronic corticosteroid treatment longer than 8 weeks duration for adverse
             events within 6 months.