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

• Sponsor: Immunocore Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01211262
• Collaborator: (none)
• Enrollment: 84
• Locations: 9
• Arms: 2
• Actual Duration (Months): 76.6
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Melanoma	Drug: IMCgp100	Phase 1

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

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Actual Study Start Date: Sep 28, 2010
• Actual Primary Completion Date: Feb 16, 2016
• Actual Study Completion Date: Feb 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IMCgp100 weekly dosing regimen Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 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 participants will be treated at the RP2D or MTD.; Other Names: 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.	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 participants will be treated at the RP2D or MTD.; Other Names: ImmTACgp100

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part) [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

2. MTD of IMCgp100 Administered Daily (Dose Escalation Part) [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

3. Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) [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.

4. Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) [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.

5. Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) [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.

6. Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) [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.

7. Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) [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.

8. Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs) [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.

9. Number of Participants Experiencing Clinically Significant Vital Signs [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.

10. Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease) [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.

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

Secondary Outcome Measures

1. Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part) [28 months]

   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.

2. Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts) [28 months]

   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.

3. Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation) [Day 1, Cycle 1]

   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

4. Estimated Cmax of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts) [Day 1, Cycle 1]

   The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.

5. Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts) [Day 1, Cycle 1]

   The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: mcg = micrograms

6. Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) [Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50]

   The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.

7. Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) [Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50]

   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.

8. Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) [Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50]

   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.

9. Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) [Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50]

   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.

10. Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation) [Cycle 1: Day 1]

    The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.

11. Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation) [Day 1, Cycle 1]

    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.

12. AUC of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts) [Day 1, Cycle 1]

    The AUC, measured in h*pg/ml, is a method of measurement of the total exposure of a drug in blood.

13. AUC of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts) [Day 1, Cycle 1]

    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.

14. AUC of IMCgp100 of 50 mcg Flat Dose (Dose Escalation and Dose Expansion Parts) [Day 1, Cycle 1]

    The AUC (measured in h*pg/ml) is a method of measurement of the total exposure of a drug in blood.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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. Participants 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 localized radiotherapy has been applied, treatment with IMCgp100 can be commenced after a two week period.

3. Human leukocyte antigen (HLA) A2 positive.

4. ≥ 18 years old.

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

6. 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.

7. Life expectancy > 3 months.

8. Blood tests within the following parameters:

9. Platelet count ≥ 100 x10⁹/L

10. Hemoglobin ≥ 9g/dL (blood transfusion to achieve this level is permitted)

11. Calculated creatinine clearance ≥ 50 mL/min using the modified Cockroft-Gault equation

12. Neutrophil count ≥1x10⁹/L

13. Lymphocyte count ≥ 0.5x10⁹/L

14. 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.

15. 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.

16. 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.

17. Able to give informed consent.

Exclusion Criteria:

Participants 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. Participants with corrected QT interval (QTc) calculated by Bazetts or locally preferred formula which is greater than 500 ms.

8. Has hepatic function as follows:

9. Aspartate aminotransferase > 2.5 x upper limit of normal (ULN)

10. Alanine aminotransferase > 2.5 x ULN

11. Bilirubin > 2.0 x ULN

12. Prothrombin time or partial thromboplastin time > 1.5 x ULN

13. Bleeding diathesis

14. Immunosuppressive condition or treatment including previous transplantation, splenectomy or known human immunodeficiency virus (HIV) infection.

15. Has a history of adult seizures.

16. Participants with evidence of a raised intracranial pressure in Arm 2 of the study who will have a cerebrospinal fluid sample taken.

17. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Angeles Clinic	Los Angeles	California	United States	90025
2	Yale Cancer Center	New Haven	Connecticut	United States	06520-8028
3	Memorial Slone Kettering Cancer Center	New York	New York	United States	10065
4	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
5	Queen Elizabeth Hospital	Birmingham		United Kingdom
6	Addenbrooke's Hospital	Cambridge		United Kingdom
7	The Beatson Institute	Glasgow		United Kingdom
8	St James Hospital	Leeds		United Kingdom
9	NIHR Biomedical Research Centre	Oxford		United Kingdom

Sponsors and Collaborators

• Immunocore Ltd

Investigators

• Study Director: Namir Hassan, PhD, Immunocore Ltd

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Immunocore Ltd
• ClinicalTrials.gov Identifier: NCT01211262
• Other Study ID Numbers: IMCgp100/01; 2010-019290-15
• First Posted: Sep 29, 2010
• Last Update Posted: Jul 8, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Immunocore Ltd: Melanoma; Phase I; Biologic
• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Pre-assignment Detail	All-patients population and safety population both comprised 84 participants who enrolled in the study and who also received at least one IMCgp100 dose; the all-patients and safety population for Arm 1 was 66 participants and for Arm 2 was 18 participants. Efficacy population was 54 participants in Arm 1 and 15 participants in Arm 2.

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Period Title: Overall Study
STARTED	66	18
COMPLETED	43	8
NOT COMPLETED	23	10

Baseline Characteristics

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen	Total
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle	Total of all reporting groups
Overall Participants	66	18	84
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58.2	60.4	58.7
Sex: Female, Male (Count of Participants)
Female	25 37.9%	5 27.8%	30 35.7%
Male	41 62.1%	13 72.2%	54 64.3%
Race/Ethnicity, Customized (participants) [Number]
White	62 93.9%	17 94.4%	79 94%
Black	1 1.5%	0 0%	1 1.2%
Asian	1 1.5%	0 0%	1 1.2%
Other	2 3%	1 5.6%	3 3.6%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part)
Description	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
Time Frame	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8

Outcome Measure Data

Analysis Population Description

Safety population: all participants who received at least 1 dose of IMCgp100, up to a maximum of 600 ng/kg.

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	27
Number [ng/kg]	600

2. Primary Outcome

Title	MTD of IMCgp100 Administered Daily (Dose Escalation Part)
Description	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
Time Frame	Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8

Outcome Measure Data

Analysis Population Description

Safety population: all participants who received at least 1 dose of IMCgp100

Arm/Group Title	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Daily intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	18
Number [mcg]	50

3. Primary Outcome

Title	Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Day 1 (first dose), 30 days after the last dose

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	66	18
Number [percentage of participants]	100.0 151.5%	100.00 555.6%

4. Primary Outcome

Title	Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology)
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment.
Measure Participants	66	18
Lymphocytes	12 18.2%	1 5.6%
Hemoglobin	1 1.5%	2 11.1%
Neutrophils	1 1.5%	0 0%
CD4 Cells	1 1.5%	0 0%
Leukocytes	1 1.5%	0 0%

5. Primary Outcome

Title	Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology)
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	66	18
Lymphocytes-Grade 3	15 22.7%	2 11.1%
Lymphocytes-Grade 4	2 3%	2 11.1%
CD4 Count-Grade 3	4 6.1%	1 5.6%
CD4 Count-Grade 4	4 6.1%	1 5.6%
Hemoglobin-Grade 3	0 0%	3 16.7%
Leukocytes-Grade 3	1 1.5%	0 0%

6. Primary Outcome

Title	Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry)
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	66	18
Albumin	3 4.5%	3 16.7%
Alkaline Phosphatase	3 4.5%	1 5.6%
Aspartate Aminotransferase	1 1.5%	2 11.1%
Alanine Aminotransferase	1 1.5%	1 5.6%
Potassium	1 1.5%	1 5.6%
Calcium	0 0%	1 5.6%
Glucose	1 1.5%	0 0%
Magnesium	0 0%	1 5.6%
Sodium	0 0%	1 5.6%
Uric Acid	1 1.5%	0 0%

7. Primary Outcome

Title	Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry)
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	66	18
Sodium-Grade 3	2 3%	4 22.2%
Potassium-Grade 3	2 3%	1 5.6%
Glucose-Grade 3	1 1.5%	1 5.6%
Aspartate Aminotransferase-Grade 3	1 1.5%	0 0%
Calcium-Grade 3	0 0%	1 5.6%

8. Primary Outcome

Title	Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs)
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	66	18
Number [number of participants]	3 4.5%	0 0%

9. Primary Outcome

Title	Number of Participants Experiencing Clinically Significant Vital Signs
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	66	18
High Systolic Blood Pressure	17 25.8%	2 11.1%
Low Systolic Blood Pressure	8 12.1%	5 27.8%
High Diastolic Blood Pressure	20 30.3%	3 16.7%
Low Diastolic Blood Pressure	37 56.1%	12 66.7%
High Heart Rate	34 51.5%	12 66.7%
Low Heart Rate	8 12.1%	1 5.6%
High Temperature	33 50%	13 72.2%

10. Primary Outcome

Title	Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease)
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	66	18
Number [number of participants]	3 4.5%	1 5.6%

11. Primary Outcome

Title	Number of Participants Experiencing ≥Grade 3 Severity in Physical Examination Results (Skin Pigmentation)
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	66	18
Number [number of participants]	0 0%	0 0%

12. Secondary Outcome

Title	Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part)
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Efficacy population: only evaluable participants (those having both a baseline and post treatment sample).

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	54	15
Number [participants]	5 7.6%	1 5.6%

13. Secondary Outcome

Title	Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts)
Description	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.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Efficacy population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	66	18
Number [participants]	2 3%	1 5.6%

14. Secondary Outcome

Title	Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation)
Description	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
Time Frame	Day 1, Cycle 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetics (PK) Population: all participants who receive at least 1 dose of IMCgp100 and have at least 1 measurable PK concentration with the relevant date, time and dosing data for this sample.

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	42
15 ng/kg by-weight dose	305.50 (583.47)
45 ng/kg by-weight dose	271.33 (21.49)
135 ng/kg by-weight dose	371.79 (57.25)
270 ng/kg by-weight dose	856.35 (41.01)
405 ng/kg by-weight dose	2345.25 (35.74)
600 ng/kg by-weight dose	6188.54 (41.21)
900 ng/kg by-weight dose	8868.83 (27.92)

15. Secondary Outcome

Title	Estimated Cmax of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
Description	The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time Frame	Day 1, Cycle 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	4
Geometric Mean (Geometric Coefficient of Variation) [picograms/milliliter]	8868.83 (27.92)

16. Secondary Outcome

Title	Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
Description	The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: mcg = micrograms
Time Frame	Day 1, Cycle 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	21
20 mcg	3239.82 (20.97)
40 mcg	8316.43 (45.10)
50 mcg	8740.99 (38.01)

17. Secondary Outcome

Title	Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation)
Description	The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time Frame	Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	10
Day 1	7311 (1770)
Day 8	5726 (3605)
Day 15	6182 (1456)
Day 22	6490 (2488)
Day 29	6245 (3047)
Day 36	6396 (3474)
Day 43	6014 (1125)
Day 50	7136 (2744)

18. Secondary Outcome

Title	Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation)
Description	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.
Time Frame	Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	7
Day 1	3299 (660)
Day 8	5056 (1175)
Day 15	7981 (2278)
Day 22	6682 (1395)
Day 29	4710 (3621)
Day 36	7100 (1535)
Day 43	7240 (1906)
Day 50	6658 (1211)

19. Secondary Outcome

Title	Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation)
Description	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.
Time Frame	Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	3
Day 1	8847 (3811)
Day 8	5340 (311)
Day 15	8373 (2682)
Day 22	7445 (983)
Day 29	3288 (4614)
Day 36	8073 (1337)
Day 43	6735 (672)
Day 50	7130 (4483)

20. Secondary Outcome

Title	Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation)
Description	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.
Time Frame	Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	11
Day 1	9327 (3802)
Day 8	6414 (3653)
Day 15	7236 (3304)
Day 22	7620 (2710)
Day 29	8186 (3178)
Day 36	8425 (4594)
Day 43	6905 (4097)
Day 50	9018 (5001)

21. Secondary Outcome

Title	Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation)
Description	The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time Frame	Cycle 1: Day 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Daily Dosing Regimen
Arm/Group Description	Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Measure Participants	18
10 mcg	997.83 (38.01)
20 mcg	3599.18 (15.42)
30 mcg	3599.18 (15.42)
40 mcg	6157.90 (29.52)
50 mcg	8111.79 (27.80)

22. Secondary Outcome

Title	Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation)
Description	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.
Time Frame	Day 1, Cycle 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	42
15 ng/kg	5666.63 (434.62)
45 ng/kg	2965.10 (49.17)
135 ng/kg	2904.91 (96.95)
270 ng/kg	10649.19 (40.82)
405 ng/kg	33332.31 (43.57)
600 ng/kg	63507.24 (43.97)
900 ng/kg	97724.58 (29.49)

23. Secondary Outcome

Title	AUC of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
Description	The AUC, measured in h*pg/ml, is a method of measurement of the total exposure of a drug in blood.
Time Frame	Day 1, Cycle 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	4
Geometric Mean (Geometric Coefficient of Variation) [hours * picograms/milliliter]	97724.58 (29.49)

24. Secondary Outcome

Title	AUC of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
Description	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.
Time Frame	Day 1, Cycle 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	10
20 mcg	3239.82 (20.97)
40 mcg	59333.15 (21.44)

25. Secondary Outcome

Title	AUC of IMCgp100 of 50 mcg Flat Dose (Dose Escalation and Dose Expansion Parts)
Description	The AUC (measured in h*pg/ml) is a method of measurement of the total exposure of a drug in blood.
Time Frame	Day 1, Cycle 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	IMCgp100 Weekly Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Measure Participants	11
Geometric Mean (Geometric Coefficient of Variation) [hours * picograms/milliliter]	73134.57 (55.88)

Adverse Events

Time Frame	Up to Day 80 (follow up)
Adverse Event Reporting Description	Adverse events were recorded from the time informed consent was obtained to 30 days after the final dose or 30 days after withdrawal from treatment. The safety population was comprised of the 84 participants who enrolled in the study and included all participants who received at least one dose of IMCgp100.
Arm/Group Title	IMCgp100 Weekly Dosing Regimen		IMCgp100 Daily Dosing Regimen
Arm/Group Description	Weekly intravenous (IV) infusions of IMCgp100 at the weekly maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) over treatment cycles of eight weeks each.		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 RP2D.
All Cause Mortality
	IMCgp100 Weekly Dosing Regimen		IMCgp100 Daily Dosing Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/66 (12.1%)		8/18 (44.4%)
Serious Adverse Events
	IMCgp100 Weekly Dosing Regimen		IMCgp100 Daily Dosing Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/66 (36.4%)		5/18 (27.8%)
Blood and lymphatic system disorders
ANAEMIA	1/66 (1.5%)	1	0/18 (0%)	0
Cardiac disorders
ATRIAL FIBRILLATION	0/66 (0%)	0	1/18 (5.6%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	1/66 (1.5%)	1	0/18 (0%)	0
ASCITES	1/66 (1.5%)	1	0/18 (0%)	0
INTESTINAL OBSTRUCTION	0/66 (0%)	0	1/18 (5.6%)	1
INTRA-ABDOMINAL HAEMORRHAGE	1/66 (1.5%)	1	0/18 (0%)	0
General disorders
ADVERSE DRUG REACTION	2/66 (3%)	2	0/18 (0%)	0
DISEASE PROGRESSION	2/66 (3%)	2	1/18 (5.6%)	1
MALAISE	1/66 (1.5%)	1	0/18 (0%)	0
PYREXIA	1/66 (1.5%)	1	0/18 (0%)	0
Immune system disorders
CYTOKINE RELEASE SYNDROME	1/66 (1.5%)	1	0/18 (0%)	0
Infections and infestations
BILIARY TRACT INFECTION	1/66 (1.5%)	2	0/18 (0%)	0
CONJUNCTIVITIS	1/66 (1.5%)	1	0/18 (0%)	0
GASTRIC INFECTION	1/66 (1.5%)	1	0/18 (0%)	0
LOWER RESPIRATORY TRACT INFECTION	1/66 (1.5%)	1	0/18 (0%)	0
WOUND INFECTION	0/66 (0%)	0	1/18 (5.6%)	1
Injury, poisoning and procedural complications
INFUSION RELATED REACTION	1/66 (1.5%)	1	0/18 (0%)	0
OVERDOSE	1/66 (1.5%)	1	0/18 (0%)	0
Investigations
LABORATORY TEST ABNORMAL	1/66 (1.5%)	1	0/18 (0%)	0
LIVER FUNCTION TEST INCREASED	2/66 (3%)	3	0/18 (0%)	0
Metabolism and nutrition disorders
DECREASED APPETITE	1/66 (1.5%)	1	0/18 (0%)	0
HYPOCALCAEMIA	1/66 (1.5%)	1	0/18 (0%)	0
HYPOPHOSPHATAEMIA	1/66 (1.5%)	1	0/18 (0%)	0
Musculoskeletal and connective tissue disorders
BACK PAIN	2/66 (3%)	2	0/18 (0%)	0
BONE PAIN	1/66 (1.5%)	1	0/18 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR HAEMORRHAGE	1/66 (1.5%)	1	0/18 (0%)	0
Nervous system disorders
APHASIA	1/66 (1.5%)	1	0/18 (0%)	0
SPINAL CORD COMPRESSION	1/66 (1.5%)	1	0/18 (0%)	0
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME	1/66 (1.5%)	1	0/18 (0%)	0
Skin and subcutaneous tissue disorders
RASH	1/66 (1.5%)	2	0/18 (0%)	0
Vascular disorders
HYPOTENSION	4/66 (6.1%)	5	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	IMCgp100 Weekly Dosing Regimen		IMCgp100 Daily Dosing Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/66 (100%)		18/18 (100%)
Blood and lymphatic system disorders
ANAEMIA	4/66 (6.1%)	4	5/18 (27.8%)	5
LEUKOCYTOSIS	3/66 (4.5%)	3	1/18 (5.6%)	1
LYMPHOPENIA	13/66 (19.7%)	13	1/18 (5.6%)	1
THROMBOCYTOPENIA	2/66 (3%)	2	4/18 (22.2%)	4
Cardiac disorders
SINUS TACHYCARDIA	5/66 (7.6%)	5	1/18 (5.6%)	1
TACHYCARDIA	7/66 (10.6%)	7	4/18 (22.2%)	4
Eye disorders
ERYTHEMA OF EYELID	0/66 (0%)	0	1/18 (5.6%)	1
EYE IRRITATION	0/66 (0%)	0	1/18 (5.6%)	1
EYE PAIN	2/66 (3%)	2	1/18 (5.6%)	1
EYELID OEDEMA	0/66 (0%)	0	1/18 (5.6%)	1
OCULAR HYPERAEMIA	2/66 (3%)	2	1/18 (5.6%)	1
PERIORBITAL OEDEMA	30/66 (45.5%)	30	11/18 (61.1%)	11
Gastrointestinal disorders
ABDOMINAL PAIN	9/66 (13.6%)	9	2/18 (11.1%)	2
ABDOMINAL PAIN UPPER	5/66 (7.6%)	5	1/18 (5.6%)	1
CONSTIPATION	14/66 (21.2%)	14	3/18 (16.7%)	3
DIARRHOEA	10/66 (15.2%)	10	5/18 (27.8%)	5
DYSPEPSIA	4/66 (6.1%)	4	1/18 (5.6%)	1
NAUSEA	34/66 (51.5%)	34	10/18 (55.6%)	10
TOOTHACHE	0/66 (0%)	0	1/18 (5.6%)	1
VOMITING	24/66 (36.4%)	24	10/18 (55.6%)	10
General disorders
ASTHENIA	1/66 (1.5%)	1	1/18 (5.6%)	1
AXILLARY PAIN	2/66 (3%)	2	1/18 (5.6%)	1
CHEST PAIN	7/66 (10.6%)	7	0/18 (0%)	0
CHILLS	17/66 (25.8%)	17	9/18 (50%)	9
FACE OEDEMA	13/66 (19.7%)	13	3/18 (16.7%)	3
FATIGUE	35/66 (53%)	35	10/18 (55.6%)	10
INFLUENZA LIKE ILLNESS	13/66 (19.7%)	13	5/18 (27.8%)	5
MALAISE	2/66 (3%)	2	1/18 (5.6%)	1
OEDEMA	4/66 (6.1%)	4	1/18 (5.6%)	1
OEDEMA PERIPHERAL	10/66 (15.2%)	10	8/18 (44.4%)	8
PAIN	2/66 (3%)	2	2/18 (11.1%)	2
PERIPHERAL SWELLING	6/66 (9.1%)	6	2/18 (11.1%)	2
PYREXIA	34/66 (51.5%)	34	13/18 (72.2%)	13
Immune system disorders
HYPERSENSITIVITY	1/66 (1.5%)	1	1/18 (5.6%)	1
Infections and infestations
ANGULAR CHEILITIS	4/66 (6.1%)	4	0/18 (0%)	0
CATHETER SITE INFECTION	0/66 (0%)	0	1/18 (5.6%)	1
CONJUNCTIVITIS	5/66 (7.6%)	5	0/18 (0%)	0
LOWER RESPIRATORY TRACT INFECTION	3/66 (4.5%)	3	2/18 (11.1%)	2
NASOPHARYNGITIS	2/66 (3%)	2	1/18 (5.6%)	1
PNEUMONIA	0/66 (0%)	0	1/18 (5.6%)	1
RASH PUSTULAR	0/66 (0%)	0	1/18 (5.6%)	1
RHINITIS	6/66 (9.1%)	6	0/18 (0%)	0
UPPER RESPIRATORY TRACT INFECTION	4/66 (6.1%)	4	1/18 (5.6%)	1
URINARY TRACT INFECTION	4/66 (6.1%)	4	1/18 (5.6%)	1
Injury, poisoning and procedural complications
CONTUSION	2/66 (3%)	2	1/18 (5.6%)	1
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED	3/66 (4.5%)	3	2/18 (11.1%)	2
BLOOD BILIRUBIN INCREASED	1/66 (1.5%)	1	1/18 (5.6%)	1
BLOOD CREATININE INCREASED	1/66 (1.5%)	1	1/18 (5.6%)	1
TRANSAMINASES INCREASED	1/66 (1.5%)	1	3/18 (16.7%)	3
WEIGHT DECREASED	1/66 (1.5%)	1	2/18 (11.1%)	2
Metabolism and nutrition disorders
DECREASED APPETITE	9/66 (13.6%)	9	0/18 (0%)	0
DEHYDRATION	4/66 (6.1%)	4	0/18 (0%)	0
HYPERGLYCAEMIA	1/66 (1.5%)	1	1/18 (5.6%)	1
HYPOALBUMINAEMIA	3/66 (4.5%)	3	2/18 (11.1%)	2
HYPOCALCAEMIA	2/66 (3%)	2	1/18 (5.6%)	1
HYPOKALAEMIA	1/66 (1.5%)	1	1/18 (5.6%)	1
HYPOMAGNESAEMIA	2/66 (3%)	2	2/18 (11.1%)	2
HYPONATRAEMIA	2/66 (3%)	2	1/18 (5.6%)	1
HYPOPHOSPHATAEMIA	5/66 (7.6%)	5	3/18 (16.7%)	3
HYPOPROTEINAEMIA	0/66 (0%)	0	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	7/66 (10.6%)	7	3/18 (16.7%)	3
BACK PAIN	14/66 (21.2%)	14	2/18 (11.1%)	2
GROIN PAIN	2/66 (3%)	2	1/18 (5.6%)	1
MUSCULOSKELETAL PAIN	3/66 (4.5%)	3	1/18 (5.6%)	1
MYALGIA	6/66 (9.1%)	6	1/18 (5.6%)	1
NECK PAIN	3/66 (4.5%)	3	2/18 (11.1%)	2
PAIN IN EXTREMITY	9/66 (13.6%)	9	1/18 (5.6%)	1
Nervous system disorders
DIZZINESS	4/66 (6.1%)	4	0/18 (0%)	0
HEADACHE	16/66 (24.2%)	16	6/18 (33.3%)	6
LETHARGY	5/66 (7.6%)	5	0/18 (0%)	0
PARAESTHESIA	10/66 (15.2%)	10	1/18 (5.6%)	1
SPEECH DISORDER	0/66 (0%)	0	1/18 (5.6%)	1
SYNCOPE	0/66 (0%)	0	1/18 (5.6%)	1
Psychiatric disorders
HALLUCINATION	0/66 (0%)	0	1/18 (5.6%)	1
INSOMNIA	4/66 (6.1%)	4	0/18 (0%)	0
Renal and urinary disorders
HYDRONEPHROSIS	0/66 (0%)	0	1/18 (5.6%)	1
POLLAKIURIA	1/66 (1.5%)	1	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	16/66 (24.2%)	16	2/18 (11.1%)	2
DYSPNOEA	6/66 (9.1%)	6	2/18 (11.1%)	2
HICCUPS	0/66 (0%)	0	1/18 (5.6%)	1
HYPOXIA	3/66 (4.5%)	3	1/18 (5.6%)	1
OROPHARYNGEAL PAIN	4/66 (6.1%)	4	1/18 (5.6%)	1
PRODUCTIVE COUGH	1/66 (1.5%)	1	1/18 (5.6%)	1
RALES	4/66 (6.1%)	4	0/18 (0%)	0
WHEEZING	2/66 (3%)	2	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
BLISTER	2/66 (3%)	2	2/18 (11.1%)	2
BLOOD BLISTER	2/66 (3%)	2	1/18 (5.6%)	1
COLD SWEAT	1/66 (1.5%)	1	1/18 (5.6%)	1
DRY SKIN	18/66 (27.3%)	18	5/18 (27.8%)	5
ERYTHEMA	17/66 (25.8%)	17	2/18 (11.1%)	2
GENERALISED ERYTHEMA	0/66 (0%)	0	1/18 (5.6%)	1
HAIR COLOUR CHANGES	7/66 (10.6%)	7	1/18 (5.6%)	1
ONYCHOCLASIS	0/66 (0%)	0	1/18 (5.6%)	1
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	2/66 (3%)	2	1/18 (5.6%)	1
PRURITUS	43/66 (65.2%)	43	16/18 (88.9%)	16
RASH	47/66 (71.2%)	47	10/18 (55.6%)	10
RASH ERYTHEMATOUS	9/66 (13.6%)	9	5/18 (27.8%)	5
RASH GENERALISED	1/66 (1.5%)	1	1/18 (5.6%)	1
RASH MACULO-PAPULAR	17/66 (25.8%)	17	6/18 (33.3%)	6
RASH PRURITIC	2/66 (3%)	2	1/18 (5.6%)	1
SKIN EXFOLIATION	19/66 (28.8%)	19	5/18 (27.8%)	5
VITILIGO	9/66 (13.6%)	9	1/18 (5.6%)	1
Vascular disorders
FLUSHING	11/66 (16.7%)	11	1/18 (5.6%)	1
HAEMORRHAGE	0/66 (0%)	0	1/18 (5.6%)	1
HYPERTENSION	7/66 (10.6%)	7	1/18 (5.6%)	1
HYPOTENSION	20/66 (30.3%)	20	7/18 (38.9%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Publication/presentation (manuscript, abstract or poster) to a journal/scientific meeting is sent to sponsor for review at least 1 month before submission who may delay submission by up to 90 days if it reasonably believes that publication of results may compromise its intellectual property rights or else insist that such data are removed. No single center/groups of centers may publish individually. Publication will not include confidential information without the permission of the sponsor.