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A Phase 1, Open Label, Dose Finding Study to Assess the Safety and Tolerability of IMCgp100, a Monoclonal T Cell Receptor Anti-CD3 scFv Fusion Protein in Patients With Advanced Malignant Melanoma

Phase 1
18 Years
Open (Enrolling)
Malignant Melanoma

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Trial Information

A Phase 1, Open Label, Dose Finding Study to Assess the Safety and Tolerability of IMCgp100, a Monoclonal T Cell Receptor Anti-CD3 scFv Fusion Protein in Patients With Advanced Malignant Melanoma

IMCgp100 is a bispecific biologic incorporating an engineered T cell receptor (TCR) specific
for a peptide antigen derived from the protein gp100 presented in the context of HLA A2 on
the surface of melanoma cells. The TCR is fused to an anti-CD3 scFv fragment that recruits
and activates non-melanoma specific T cells (killer T cells) in physical contact with the
cancer T cell. This is a Phase I study designed to assess the safety profile and establish a
tolerable dose of IMCgp100 in HLA A2 positive malignant melanoma patients. In the second
part of the trial, patients will receive an extended course of treatment with a view to
assessing the effect of the drug on disease. Patients in the dose escalation phase may also
be offered repeat treatment with a dose that has been demonstrated to be tolerable.

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. Patients 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 localised radiotherapy has been
applied, treatment with IMCgp100 can be commenced after a two week period.

3. HLA A2 positive.

4. ≥ 18 years old.

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

6. For patients in the Dose-Expansion part only, measurable disease according to RECIST
criteria. For patients in the Dose-escalation part of the study, only 'assessable
disease' is required.

7. Life expectancy >3 months.

8. Blood tests within the following parameters:

1. Platelet count ≥100 x 109/L

2. Haemoglobin ≥10g/dL

3. Calculated creatinine clearance ≥60 mL/min using the modified Cockcroft-Gault

4. Neutrophil counts ≥1x109/L

5. Lymphocyte count ≥0.5x109/L

9. Female patients 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 patients must be
postmenopausal (no menstrual period for a minimum of 12 months) or surgically

10. Male patients must be surgically sterile or willing to use a double barrier
contraception method upon enrolment, during the course of the study, and for 6 months
following the last study drug infusion.

11. Able to give informed consent.

Exclusion Criteria:

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 non-melanomatous 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. Any symptomatic ongoing 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. Patients with QTc calculated by Bazetts or
locally preferred formula which is greater than 500ms.

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 HIV infection.

11. Has a history of adult seizures.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Definition of the maximum tolerated dose and evaluation of the safety and tolerability of multiple injections of IMCgp100

Outcome Description:

The outcome measure of part 1 of the trial is the definition of the maximum tolerated dose based on dose limiting toxicity and pharmacokinetics in patients with stage IV or stage III unresectable malignant melanoma. The outcome measure of part 2 of the trial is the evaluation of the safety and tolerability of IMCgp100 following multiple IV administrations of IMCgp100 given at the dose recommended from part 1 of the study.

Outcome Time Frame:

28 months

Safety Issue:


Principal Investigator

Yvonne McGrath, PhD

Investigator Role:

Study Director

Investigator Affiliation:

Immunocore Ltd


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

September 2010

Completion Date:

December 2013

Related Keywords:

  • Malignant Melanoma
  • Melanoma
  • Phase I
  • Biologic
  • Melanoma



Mary Crowley Cancer Research CenterDallas, Texas  75246