IMCgp100-401 Rollover Study

• Sponsor: Immunocore Ltd (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02889861
• Collaborator: (none)
• Enrollment: 3
• Locations: 3
• Arm: 1
• Actual Duration (Months): 27.3
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

IMCgp100-401 is a rollover study that is designed to provide continued access to IMCgp100 for eligible participants with advanced melanoma who have previously participated in an IMCgp100 study (parent study).

Condition or Disease	Intervention/Treatment	Phase
Malignant Melanoma	Drug: IMCgp100	Phase 2

Detailed Description

IMCgp100-401 is a rollover study that is designed to provide continued access to IMCgp100 for eligible participants with advanced melanoma who have previously participated in an IMCgp100 study (parent study). Parent studies that are eligible for participants to continue to receive IMCgp100 in this rollover study must have completed and satisfied its primary endpoints or have been terminated by the Sponsor for reasons other than safety.

Eligible participants will have tolerated IMCgp100 for a minimum of 4 weeks of dosing without significant toxicities that would preclude further dosing in the opinion of the principal investigator or Sponsor.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multi-center, Rollover Study in Patients With Advanced Melanoma After Completing an IMCgp100 Clinical Study
• Actual Study Start Date: Jan 11, 2017
• Actual Primary Completion Date: Apr 22, 2019
• Actual Study Completion Date: Apr 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen 1 IMCgp100 (77 kDa bi-specific protein) weekly dosing regimen (QW)	Drug: IMCgp100; Bispecific soluble human leukocyte antigen-A2 (HLA-A2) restricted gp100-specific TCR fused to anti-CD3

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Events: Number of Participants With Treatment-Emergent Adverse Events [Up to 2 years and 4 months]

   Incidence of adverse events was presented as the number of participants with treatment-emergent adverse events (TEAEs). TEAEs were defined as adverse events (AEs) that started or worsened in severity from the date of first dose of the rollover study (regardless of time) up until 90 days after the last dose of study drug of this rollover study. Participants with multiple events in the same category were counted only once in that category. Participants with events in more than 1 category were counted once in each of those categories. TEAEs indicated considered related to IMCgp100 were determined by the investigator to be possibly related or related to study drug.

Secondary Outcome Measures

1. Tolerability: Dose Interruptions by Participant - Number of Cycles [Up to 2 years and 4 months]

   Tolerability of study treatment was assessed by summarizing the number of treatment dose interruptions, characterized in part by number of cycles started and completed in the rollover study (22 days per cycle).

2. Tolerability: Dose Interruptions by Participant - Duration [Up to 2 years and 4 months]

   Tolerability of study treatment was assessed by summarizing the number of treatment dose interruptions, characterized in part by duration of interruption and treatment.

3. Tolerability: Dose Reductions by Participant - Actual Total Dose Received [Up to 2 years and 4 months]

   Tolerability of study treatment was assessed by summarizing actual total dose received in micrograms in the rollover study.

4. Tolerability: Dose Reductions by Participant - Dose Intensity [Up to 2 years and 4 months]

   Tolerability of study treatment was assessed by summarizing dose intensity, described as actual dose received/actual duration (micrograms per week) in the rollover study.

5. Tolerability: Dose Reductions by Participant - Relative Dose Intensity [Up to 2 years and 4 months]

   Tolerability of study treatment was assessed by summarizing the relative dose intensity, described as the ratio of dose intensity to planned dose/planned duration in the rollover study.

6. Overall Survival Status of All Participants Treated With IMCgp100: Number of Months [Up to 2 years and 4 months]

   This endpoint was used to estimate the overall survival (OS) in participants treated with IMCgp100. OS is defined as the time from the date of first dose of study drug in the parent study until death due to any cause. Any participant not known to have died at the time of analysis was right-censored based on the last recorded date on which the participant was known to be alive, i.e. the latest of (i) the "Date of death or Last contact" (for those participants still alive) on the End of Study electronic case report form page and (ii) "Date patient last known to be alive" on the Survival Follow Up eCRF page. Number of days was then converted to months.

7. Assessments of Anti-IMCgp100 Antibody Formation: Number of Participants With Anti-IMCgp100 Antibody Formation [Up to 2 years and 4 months]

   The concentration/AE - immunogenicity relationship was explored graphically, and tabulated to characterize a relationship between the changes from screening immunogenicity presence and serum concentration of IMCgp100.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Participant is currently participating in an Immunocore-sponsored study of IMCgp100 and is actively receiving IMCgp100. Participant must have fulfilled all required assessments in the parent study (unless the study is being terminated)

2. Participant is currently receiving clinical benefit from the treatment with IMCgp100, as determined by the principal investigator from the parent study

3. Participant has demonstrated compliance with the parent study requirements, as assessed by the principal investigator and participant is able to comply with the necessary visits and assessments as part of the rollover study

4. Written informed consent must be obtained prior to enrolling in the rollover study and receiving the study treatment. If consent cannot be expressed in writing, then the consent must be formally documented and witnessed, ideally via an independent trusted witness

Exclusion Criteria:

1. Participant has been permanently discontinued from any IMCgp100 study or from IMCgp100 treatment in the parent study due to unequivocal progressive disease, unacceptable toxicity, non-compliance to study procedures, withdrawal of consent, or any other reason

2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test

3. Women of child-bearing potential who are sexually active with a non-sterilized male partner, defined as all women physiologically capable of becoming pregnant, unless they are using 2 methods of highly effective contraception from Screening, and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician. Highly effective methods include barrier methods, intrauterine devices or hormonal methods. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Women of child-bearing potential must have a negative serum pregnancy test at Screening. Otherwise, female participants must be post-menopausal (no menstrual period for at least 12 months prior to Screening), or surgically sterile

4. Male participants who are not surgically sterile unless they are using a double barrier contraception method from enrollment through treatment and for 6 months following administration of the last dose of study drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Slone Kettering Cancer Center	New York	New York	United States	10065
2	Dept of Oncology & Haematology, Churchill Hospital	Oxford	Oxfordshire	United Kingdom	OX3 7LJ
3	Dept of Medical Oncology, Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 OYN

Sponsors and Collaborators

• Immunocore Ltd

Investigators

None specified.

Study Documents (Full-Text)

• Statistical Analysis Plan - May 9, 2019
• Study Protocol - Nov 7, 2016

More Information

Publications

None provided.

• Responsible Party: Immunocore Ltd
• ClinicalTrials.gov Identifier: NCT02889861
• Other Study ID Numbers: IMCgp100-401
• First Posted: Sep 7, 2016
• Last Update Posted: Jul 27, 2020
• Last Verified: Jul 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Immunocore Ltd: Uveal melanoma; Cutaneous melanoma
• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Recruitment Details	Eligible participants have tolerated IMCgp100 (77 kDa bi-specific protein) for a minimum of 4 weeks of dosing without significant toxicities that would preclude further dosing in the opinion of the principal investigator or Sponsor.
Pre-assignment Detail	Participants were eligible for enrollment in this study from parent studies that have completed and satisfied its primary endpoints or have been terminated by the Sponsor for reasons other than safety.

Arm/Group Title	Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)
Period Title: Overall Study
STARTED	3
COMPLETED	1
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW) IMCgp100: Bispecific soluble HLA-A2 restricted gp100-specific TCR fused to anti-CD3
Overall Participants	3
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 33.3%
>=65 years	2 66.7%
Sex: Female, Male (Count of Participants)
Female	1 33.3%
Male	2 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	3 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	3 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Incidence of Adverse Events: Number of Participants With Treatment-Emergent Adverse Events
Description	Incidence of adverse events was presented as the number of participants with treatment-emergent adverse events (TEAEs). TEAEs were defined as adverse events (AEs) that started or worsened in severity from the date of first dose of the rollover study (regardless of time) up until 90 days after the last dose of study drug of this rollover study. Participants with multiple events in the same category were counted only once in that category. Participants with events in more than 1 category were counted once in each of those categories. TEAEs indicated considered related to IMCgp100 were determined by the investigator to be possibly related or related to study drug.
Time Frame	Up to 2 years and 4 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAF) includes all participants who have received at least 1 full or partial dose of IMCgp100.

Arm/Group Title	Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)
Measure Participants	3
Any TEAE	2 66.7%
Any TEAE of CTCAE Grade ≥3	2 66.7%
Any TEAE related to IMCgp100 by Investigator	2 66.7%
Any TEAE of CTCAE Grade ≥3 and related to IMCgp100	1 33.3%
Any serious TEAE	0 0%
Any serious TEAE related to IMCgp100	0 0%
Any TEAE leading to death	0 0%
Any TEAE leading to discontinuation of study drug	0 0%

2. Secondary Outcome

Title	Tolerability: Dose Interruptions by Participant - Number of Cycles
Description	Tolerability of study treatment was assessed by summarizing the number of treatment dose interruptions, characterized in part by number of cycles started and completed in the rollover study (22 days per cycle).
Time Frame	Up to 2 years and 4 months

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Participant 4001001 Regimen 1	Participant 4002001 Regimen 1	Participant 4003001 Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)	MCgp100 weekly dosing regimen (QW)	MCgp100 weekly dosing regimen (QW)
Measure Participants	1	1	1
Number of cycles started (rollover)	2	26	18
Number of cycles completed (rollover)	1	25	17

3. Secondary Outcome

Title	Tolerability: Dose Interruptions by Participant - Duration
Description	Tolerability of study treatment was assessed by summarizing the number of treatment dose interruptions, characterized in part by duration of interruption and treatment.
Time Frame	Up to 2 years and 4 months

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Participant 4001001 Regimen 1	Participant 4002001 Regimen 1	Participant 4003001 Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)	IMCgp100 weekly dosing regimen (QW)	IMCgp100 weekly dosing regimen (QW)
Measure Participants	1	1	1
Duration of IMCgp100 treatment on rollover study	43	728	505
Duration of interruption on rollover study	0	0	0
Duration of IMCgp100 treatment from parent study	423	1156	960

4. Secondary Outcome

Title	Tolerability: Dose Reductions by Participant - Actual Total Dose Received
Description	Tolerability of study treatment was assessed by summarizing actual total dose received in micrograms in the rollover study.
Time Frame	Up to 2 years and 4 months

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Participant 4001001 Regimen 1	Participant 4002001 Regimen 1	Participant 4003001 Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)	IMCgp100 weekly dosing regimen (QW)	IMCgp100 weekly dosing regimen (QW)
Measure Participants	1	1	1
Number [Micrograms]	350	5100	3500

5. Secondary Outcome

Title	Tolerability: Dose Reductions by Participant - Dose Intensity
Description	Tolerability of study treatment was assessed by summarizing dose intensity, described as actual dose received/actual duration (micrograms per week) in the rollover study.
Time Frame	Up to 2 years and 4 months

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Participant 4001001 Regimen 1	Participant 4002001 Regimen 1	Participant 4003001 Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)	IMCgp100 weekly dosing regimen (QW)	IMCgp100 weekly dosing regimen (QW)
Measure Participants	1	1	1
Number [Micrograms per week]	57.0	49.0	48.5

6. Secondary Outcome

Title	Tolerability: Dose Reductions by Participant - Relative Dose Intensity
Description	Tolerability of study treatment was assessed by summarizing the relative dose intensity, described as the ratio of dose intensity to planned dose/planned duration in the rollover study.
Time Frame	Up to 2 years and 4 months

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Participant 4001001 Regimen 1	Participant 4002001 Regimen 1	Participant 4003001 Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)	IMCgp100 weekly dosing regimen (QW)	IMCgp100 weekly dosing regimen (QW)
Measure Participants	1	1	1
Number [Percent]	100.0	100.0	100.0

7. Secondary Outcome

Title	Overall Survival Status of All Participants Treated With IMCgp100: Number of Months
Description	This endpoint was used to estimate the overall survival (OS) in participants treated with IMCgp100. OS is defined as the time from the date of first dose of study drug in the parent study until death due to any cause. Any participant not known to have died at the time of analysis was right-censored based on the last recorded date on which the participant was known to be alive, i.e. the latest of (i) the "Date of death or Last contact" (for those participants still alive) on the End of Study electronic case report form page and (ii) "Date patient last known to be alive" on the Survival Follow Up eCRF page. Number of days was then converted to months.
Time Frame	Up to 2 years and 4 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) comprises all participants assigned to treatment, who received at least 1 full or partial dose of IMCgp100.

Arm/Group Title	Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)
Measure Participants	3
Baseline to Death	27.0
Baseline to Study Terminated by Sponsor	41.0
Baseline to Alive	41.0

8. Secondary Outcome

Title	Assessments of Anti-IMCgp100 Antibody Formation: Number of Participants With Anti-IMCgp100 Antibody Formation
Description	The concentration/AE - immunogenicity relationship was explored graphically, and tabulated to characterize a relationship between the changes from screening immunogenicity presence and serum concentration of IMCgp100.
Time Frame	Up to 2 years and 4 months

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)
Measure Participants	3
Number [participants]	2 66.7%

Adverse Events

Time Frame	Up to 2 years and 4 months
Adverse Event Reporting Description	All participants who received any treatment with IMCgp100 were considered evaluable for safety. All AEs, regardless of study drug relationship, were collected through the 30-day Safety Follow up Period.
Arm/Group Title	Regimen 1
Arm/Group Description	IMCgp100 weekly dosing regimen (QW)
All Cause Mortality
	Regimen 1
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Serious Adverse Events
	Regimen 1
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	Regimen 1
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
Eye disorders
Blepharitis	1/3 (33.3%)	1
Gastrointestinal disorders
Constipation	1/3 (33.3%)	1
Gastrooesophageal reflux disease	1/3 (33.3%)	1
Vomiting	1/3 (33.3%)	2
General disorders
Chills	1/3 (33.3%)	1
Infections and infestations
Upper respiratory tract infection	1/3 (33.3%)	1
Investigations
ALT increased	1/3 (33.3%)	1
AST increased	1/3 (33.3%)	2
Lipase increased	1/3 (33.3%)	5
White blood cell count decreased	1/3 (33.3%)	2
Metabolism and nutrition disorders
Hypoalbuminaemia	1/3 (33.3%)	2
Hypomagnesaemia	1/3 (33.3%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	1/3 (33.3%)	2
Vascular disorders
Hypertension	1/3 (33.3%)	6

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.