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

NCT01211262 | Completed Phase 1 Results DMC

• 2 other identifiers: IMCgp100/012010-019290-15
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 9

Brief 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.

Conditions

Malignant Melanoma

Keywords

Melanoma; Phase I; Biologic

Outcome Measures

Primary Outcomes (11)

• Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part)

  The maximum tolerated dose (MTD) for IMCgp100 administered by weekly dosing was determined based on the frequency of dose-limiting toxicity (DLT) occurring during Days 1 to 8. Participants presented at MTD in the dose escalation phase. Abbreviations: ng/kg=nanograms/kilogram

  Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8

• MTD of IMCgp100 Administered Daily (Dose Escalation Part)

  The MTD for IMCgp100 administered by daily dosing was determined based on the frequency of DLT occurring during Days 1 to 8. The 50 mcg dose was the RP2D for daily dosing, as the MTD was not achieved. Abbreviations: mcg=micrograms

  Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8

• Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

  Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) with an onset date after the date of first dose and within 30 days after the last administration of study medication in either treatment arm. AEs with missing date of onset were considered treatment emergent.

  Day 1 (first dose), 30 days after the last dose

• Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology)

  Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

  28 months

• Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology)

  Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Laboratory parameter abnormalities were graded by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

  28 months

• Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry)

  Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

  28 months

• Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry)

  Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Laboratory parameter abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

  28 months

• Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs)

  Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose.

  28 months

• Number of Participants Experiencing Clinically Significant Vital Signs

  Vital signs included temperature, blood pressure, respiration rate, and heart rate. Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Blood pressure and heart rate were measured using a recording device with an appropriate cuff size. Temperature and respiration rate were measured as per clinical practice. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

  28 months

• Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease)

  Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

  28 months

• Number of Participants Experiencing ≥Grade 3 Severity in Physical Examination Results (Skin Pigmentation)

  Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

  28 months

Secondary Outcomes (14)

• Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part)

  28 months

• Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts)

  28 months

• Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation)

  Day 1, Cycle 1

• Estimated Cmax of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)

  Day 1, Cycle 1

• Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)

  Day 1, Cycle 1

Study Arms (2)

IMCgp100 weekly dosing regimen

EXPERIMENTAL

Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.

Drug: IMCgp100

IMCgp100 daily dosing regimen

EXPERIMENTAL

Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.

Drug: IMCgp100

Interventions

IMCgp100 DRUG

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.

Also known as: ImmTACgp100

IMCgp100 daily dosing regimen; IMCgp100 weekly dosing regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Human leukocyte antigen (HLA) A2 positive.
• ≥ 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• 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.
• Life expectancy \> 3 months.
• Blood tests within the following parameters:
• Platelet count ≥ 100 x10⁹/L
• Hemoglobin ≥ 9g/dL (blood transfusion to achieve this level is permitted)
• Calculated creatinine clearance ≥ 50 mL/min using the modified Cockroft-Gault equation
• Neutrophil count ≥1x10⁹/L
• Lymphocyte count ≥ 0.5x10⁹/L
• 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.
• 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.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded from the study:
• Symptomatic brain metastases that are unstable, require steroids, or that have required radiation within the last 28 days.
• 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.
• 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.
• Uveitis.
• 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.
• Has an ejection fraction \< 50%.
• 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.
• Has hepatic function as follows:
• Aspartate aminotransferase \> 2.5 x upper limit of normal (ULN)
• Alanine aminotransferase \> 2.5 x ULN
• Bilirubin \> 2.0 x ULN
• Prothrombin time or partial thromboplastin time \> 1.5 x ULN
• Bleeding diathesis
• Immunosuppressive condition or treatment including previous transplantation, splenectomy or known human immunodeficiency virus (HIV) infection.

Sponsors & Collaborators

• Immunocore Ltd: lead

Study Sites (9)

The Angeles Clinic

Los Angeles, California, 90025, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

Memorial Slone Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

The Beatson Institute

Glasgow, United Kingdom

Location

St James Hospital

Leeds, United Kingdom

Location

NIHR Biomedical Research Centre

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Chris Holland, Executive Director Head of Biostatistics
• Organization: Immunocore, LLC

chris.holland2@immunocore.com

1-267-589-9204

Study Officials

• Namir Hassan, PhD

  Immunocore Ltd

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2010
• First Posted: September 29, 2010
• Study Start: September 28, 2010
• Primary Completion: February 16, 2016
• Study Completion: February 16, 2017
• Last Updated: July 8, 2020
• Results First Posted: July 8, 2020

Record last verified: 2020-07

Locations

GB (5); US (4)