Malignant MelanomaPhase 1NCT01211262
Study to Assess the Tolerability of a Bispecific Targeted Biologic IMCgp100 in Malignant Melanoma
A Phase 1 study testing IMCgp100 in people with Malignant Melanoma, run by Immunocore Ltd at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- IMCgp100
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 28 Sep 2010to 16 Feb 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Participants 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 participants 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.
- Able to give informed consent.
Who cannot join
- 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.
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- 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.
- Has a history of adult seizures.
- Participants with evidence of a raised intracranial pressure in Arm 2 of the study who will have a cerebrospinal fluid sample taken.
- Participants receiving chronic corticosteroid treatment (longer than 8 weeks duration) for management of pre-existing adverse events at any dose, or participants with a history of chronic corticosteroid treatment longer than 8 weeks duration for adverse events within 6 months.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United Kingdom5 sites
Queen Elizabeth Hospital
Birmingham
Addenbrooke's Hospital
Cambridge
The Beatson Institute
Glasgow
St James Hospital
Leeds
NIHR Biomedical Research Centre
Oxford
United States4 sites
The Angeles Clinic
Los Angeles, California, 90025
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Yale Cancer Center
New Haven, Connecticut, 06520-8028
Memorial Slone Kettering Cancer Center
New York, New York, 10065
About this study
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
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.
Read the 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, participants will receive an extended course of treatment with a view to assessing the effect of the drug on disease.
- Conditions
- Malignant Melanoma
- Being tested
- IMCgp100
- Keywords
- Melanoma, Phase I, Biologic
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMCgp100Drug
Also called ImmTACgp100
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.
| Study group | Role | What they receive |
|---|---|---|
| IMCgp100 weekly dosing regimen | Experimental | Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each. Receives: 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. Receives: Drug: IMCgp100 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
The best overall response was assigned as complete response (CR), partial response (PR), minor response, stable disease, progressive disease (PD) or not evaluable (NE) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Measured: 28 months
Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts)
To provide a comprehensive anti-drug antibody (ADA) summary for the study, individual participant data were combined and assessed as distinct groups based on characteristics of their ADA response. Evaluable participants were those with post-drug administration samples. ADA prevalence (pre- existing antibody response) was measured as the number of baseline-positive participant out of all participants who provided baseline samples. Overall ADA incidence was calculated based on the combined number of treatment-boosted and treatment-induced ADA-positive participants. The treatment-induced incidence was determined as the number of ADA- positive participants of those that were ADA-negative at baseline; while treatment-boosted incidence was determined as the number of participants with an ADA titer increase equal to or greater than the minimum significant dilution (3-fold) of the assay.
Measured: 28 months
Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation)
The maximum plasma concentration (Cmax) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: ng/kg = nanograms/kilogram
Measured: Day 1, Cycle 1
Estimated Cmax of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Measured: Day 1, Cycle 1
Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: mcg = micrograms
Measured: Day 1, Cycle 1
Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Measured: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. On Day 1, IMCgp100 20 mcg was given, IMCgp100 30 mcg was administered on Day 8, and IMCgp100 50 mcg was dosed on Days 15 and after.
Measured: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. This dosing regimen was implemented following the Urgent Safety Measure to adapt the dosing in the Phase 1 study that dropped Dose 1 to 40 mcg from the identified 50 mcg RP2D.
Measured: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The RP2D identified in this study following review of all safety and pharmacokinetic data in the dose escalation of the Phase 1 study was the 50 mcg flat dose.
Measured: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Measured: Cycle 1: Day 1
Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation)
The area under the concentration-time curve (AUC), measured in hours by picograms per milliliter ( h*pg/ml) is a method of measurement of the total exposure of a drug in blood.
Measured: Day 1, Cycle 1
AUC of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
The AUC, measured in h*pg/ml, is a method of measurement of the total exposure of a drug in blood.
Measured: Day 1, Cycle 1
AUC of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
The AUC (measured in h*pg/ml) is a method of measurement of the total exposure of a drug in blood. Participants in the 20 mcg and 40 mcg dose groups received intra-participant dose-escalation up to 50 mcg on Day 15.
Measured: Day 1, Cycle 1
AUC of IMCgp100 of 50 mcg Flat Dose (Dose Escalation and Dose Expansion Parts)
The AUC (measured in h*pg/ml) is a method of measurement of the total exposure of a drug in blood.
Measured: Day 1, Cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2010 (estimated)
- Study start28 Sep 2010
- Primary completion16 Feb 2016
- Study completion16 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Immunocore Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Namir Hassan, PhD, Study director, Immunocore Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01211262
- Sponsor's protocol ID
- IMCgp100/01
- Other IDs
- 2010-019290-15
- Status last verified
- Jul 2020
- First submitted
- 28 Sep 2010
- Last updated
- 8 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01211262
- Acronym / sponsor ID
- IMCgp100/01
- Conditions
- Malignant Melanoma
- Keywords
- Melanoma, Phase I, Biologic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Immunocore LtdIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2010 (actual)
- Primary completion
- 16 Feb 2016 (actual)
- Study completion
- 16 Feb 2017 (actual)
- First posted
- 29 Sep 2010 (estimated)
- Results
- Posted 8 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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, participants will receive an extended course of treatment with a view to assessing the effect of the drug on disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IMCgp100 weekly dosing regimen | Experimental | Drug: IMCgp100Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each. |
| IMCgp100 daily dosing regimen | Experimental | Drug: IMCgp100Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMCgp100Also: ImmTACgp100For 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. | Drug | IMCgp100 daily dosing regimen, IMCgp100 weekly dosing regimen |
Primary outcome
Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part)
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
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
MTD of IMCgp100 Administered Daily (Dose Escalation Part)
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
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
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
Time frame: Day 1 (first dose), 30 days after the last dose
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.
Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology)
Time frame: 28 months
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.
Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology)
Time frame: 28 months
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.
Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry)
Time frame: 28 months
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.
Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry)
Time frame: 28 months
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.
Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs)
Time frame: 28 months
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.
Number of Participants Experiencing Clinically Significant Vital Signs
Time frame: 28 months
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.
Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease)
Time frame: 28 months
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.
Number of Participants Experiencing ≥Grade 3 Severity in Physical Examination Results (Skin Pigmentation)
Time frame: 28 months
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.
14 secondary outcomes
Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part)
Time frame: 28 months
Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts)
Time frame: 28 months
Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation)
Time frame: Day 1, Cycle 1
Estimated Cmax of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
Time frame: Day 1, Cycle 1
Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
Time frame: Day 1, Cycle 1
Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation)
Time frame: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation)
Time frame: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation)
Time frame: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation)
Time frame: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation)
Time frame: Cycle 1: Day 1
Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation)
Time frame: Day 1, Cycle 1
AUC of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
Time frame: Day 1, Cycle 1
AUC of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
Time frame: Day 1, Cycle 1
AUC of IMCgp100 of 50 mcg Flat Dose (Dose Escalation and Dose Expansion Parts)
Time frame: Day 1, Cycle 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Namir Hassan, PhD study director
Immunocore Ltd
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IMCgp100 in people with Malignant Melanoma, run by Immunocore Ltd at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part) (time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2020.