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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd
ClinicalTrials.gov Identifier:
NCT01211262
First received: September 28, 2010
Last updated: February 10, 2016
Last verified: February 2016
  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 establish the best dosing schedule for the drug and 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.


Enrollment: 84
Study Start Date: September 2010
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: July 2016 (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/recommended phase II dose (RP2D) over treatment cycles of eight weeks each.
Drug: IMCgp100
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 patients will be treated at the RP2D or MTD.
Other Name: ImmTACgp100
Experimental: IMCgp100 daily dosing regimen
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six week treatment cycle at the MTD/daily recommended phase II dose (RP2D).
Drug: IMCgp100
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 patients will be treated at the RP2D or 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. 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.
  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. Measurable disease according to RECIST 1.1 criteria. Patients 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. Haemoglobin ≥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 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. Patients 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 patients 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:

Patients 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. 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.
  12. Patients with evidence of a raised intracranial pressure in Arm 2 of the study who will have a CSF sample taken.
  13. Patients receiving chronic corticosteroid treatment (longer than 8 weeks duration) for management of pre-existing adverse events at any dose, or patients with a history of chronic corticosteroid treatment longer than 8 weeks duration for adverse events within 6 months.
  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

Locations
United States, California
The Angeles Clinic
Los Angeles, California, United States, 90025
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520-8028
United States, New York
Memorial Slone Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United Kingdom
Queen Elizabeth Hospital
Birmingham, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
The Beatson Institute
Glasgow, United Kingdom
St James Hospital
Leeds, United Kingdom
NIHR Biomedical Research Centre
Oxford, United Kingdom
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: February 10, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Immunocore Ltd:
Melanoma
Phase I
Biologic

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

ClinicalTrials.gov processed this record on February 10, 2016