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.
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 antibody single-chain
variable fragment (scFv) 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. The study has two treatment arms with different treatment
schedules, weekly or daily dosing. Each treatment arm in the study has two parts. In the
first part, dose escalation, the safety and tolerability of the drug are examined and the
optimal dose of drug is established. 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.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Drug : IMCgp100
Study Arm Groups : IMCgp100 weekly dosing regimen, IMCgp100 daily dosing regimen
See Interventions above
- Definition of the maximum tolerated dose (MTD) and evaluation of the safety and tolerability of multiple injections of IMCgp100 for each of two treatment regimens (weekly dosing and daily dosing); 28 months
- Characterisation of the pharmacokinetics and changes in tumour burden following IMCgp100 administration; 28 months
Sorry, this information is not available
This is available on the Clinicaltrials.gov
18 Years - N/A
- 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.
This is in the inclusion criteria above
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
Not available for this trial
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