Study to Assess the Tolerability of a Bispecific Targeted Biologic IMCgp100 in Malignant Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Immunocore Ltd
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd
ClinicalTrials.gov Identifier:
NCT01211262
First received: September 28, 2010
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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 look for signals that the drug is working as intended.


Condition Intervention Phase
Malignant Melanoma
Drug: IMCgp100
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Immunocore Ltd:

Primary Outcome Measures:
  • 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) [ Time Frame: 28 months ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Characterisation of the pharmacokinetics and changes in tumour burden following IMCgp100 administration [ Time Frame: 28 months ] [ Designated as safety issue: Yes ]
    The secondary outcome measures for this trial are the characterisation of the pharmacokinetics of IMCgp100 following single and repeat administration, evaluation of the incidence of anti-drug antibodies and the assessment of tumour burden following IMCgp100 infusion.


Estimated Enrollment: 80
Study Start Date: September 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMCgp100 weekly dosing regimen
Weekly IV infusions of IMCgp100 at the weekly MTD of 50 ug total dose administered over treatment cycles of eight weeks.
Drug: IMCgp100
For each arm the study will be divided into two parts: In part 1, dose escalation, the MTD for each dosing regimen will be established. In part 2, dose expansion, a cohort of patients will be treated at MTD.
Other Name: ImmTACgp100
Experimental: IMCgp100 daily dosing regimen
Daily IV infusions of IMCgp100 administered on days 1 to 4 and 22 to 25 of a six week treatment cycle. Dose escalation is currently underway to establish daily dosing MTD. Planned dosing will be between 10 ug and 50 ug.
Drug: IMCgp100
For each arm the study will be divided into two parts: In part 1, dose escalation, the MTD for each dosing regimen will be established. In part 2, dose expansion, a cohort of patients will be treated at MTD.
Other Name: ImmTACgp100

Detailed Description:

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. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. 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 equation
    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 sterile.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01211262

Contacts
Contact: Namir Hassan, PhD trials@immunocore.com

Locations
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520-8028
Contact: Matthew Madura    203-737-8367    matthew.madura@yale.edu   
Principal Investigator: Mario Sznol, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Drug Development Unit referral line    615-339-4214      
Principal Investigator: Jeffrey R Infante, MD         
United Kingdom
Queen Elizabeth Hospital Recruiting
Birmingham, United Kingdom
Contact: Neil Steven, PhD, FRCP         
Principal Investigator: Neil Steven, PhD, FRCP         
Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom
Contact: Pippa G Corrie, PhD, FRCP         
Principal Investigator: Pippa G Corrie, PhD, FRCP         
The Beatson Institute Recruiting
Glasgow, United Kingdom
Contact: Jeff Evans, MD, FRCP         
Principal Investigator: Jeff Evans, MD, FRCP         
St James Hospital Recruiting
Leeds, United Kingdom
Contact: Clive Mulatero, PhD, MRCP         
Principal Investigator: Clive Mulatero, PhD, MRCP         
NIHR Biomedical Research Centre Recruiting
Oxford, United Kingdom
Contact: Mark R Middleton, PhD, FRCP         
Principal Investigator: Mark R Middleton, PhD, FRCP         
Sponsors and Collaborators
Immunocore Ltd
Investigators
Study Director: Namir Hassan, PhD Immunocore Ltd
  More Information

No publications provided

Responsible Party: Immunocore Ltd
ClinicalTrials.gov Identifier: NCT01211262     History of Changes
Other Study ID Numbers: IMCgp100/01, 2010-019290-15
Study First Received: September 28, 2010
Last Updated: July 30, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Immunocore Ltd:
Melanoma
Phase I
Biologic

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 21, 2014