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A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02570308
Recruitment Status : Active, not recruiting
First Posted : October 7, 2015
Results First Posted : September 1, 2021
Last Update Posted : March 21, 2022
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd

Brief Summary:
IMCgp100-102 is a Phase I/II study of the weekly intra-patient escalation dose regimen with IMCgp100 as a single agent in participants with metastatic uveal melanoma (mUM). According to this regimen, all participants in the trial received 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation commenced at the third weekly dose at C1D15. The Phase I testing of the intra-patient escalation dosing regimen is designed to achieve a higher exposure and maximal plasma concentration of IMCgp100 after doses at Cycle 1 Day 15 (C1D15) and thereafter.

Condition or disease Intervention/treatment Phase
Uveal Melanoma Drug: IMCgp100 Phase 1 Phase 2

Detailed Description:

This is a Phase I/II clinical study of IMCgp100 in participants with advanced uveal melanoma.

This is a Phase I/II study of IMCgp100 administered on a weekly basis with an intra-patient escalation dosing regimen. The intra-patient escalation occurred at the third weekly dose on Cycle 1 Day 15 (C1D15). According to this regimen, all participants in the trial received 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW), and then a dose escalation commenced at the third weekly dose at C1D15 with the goal to achieve a long-term dosing regimen at a dose higher than that identified for the weekly dosing regimen (RP2D-QW). The dose escalation identified the intra-patient escalation regimen (RP2D-IE).

The Phase I portion of the study was a standard 3+3 dose escalation design.The recommended Phase II dose of the intra-patient escalation dose regimen (RP2D-IE) was identified and expansion cohorts in metastatic uveal melanoma was accrued based on prior therapy.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 146 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Using the Intra-patient Escalation Dosing Regimen in Patients With Advanced Uveal Melanoma
Study Start Date : February 2016
Actual Primary Completion Date : June 30, 2020
Estimated Study Completion Date : March 20, 2024


Arm Intervention/treatment
Experimental: Dose escalation
Dose escalation cohorts of the intra-patient escalation regimen.
Drug: IMCgp100
Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3
Other Names:
  • Tebentafusp
  • Kimmtrak

Experimental: Dose expansion
Dose expansion cohort with the recommended phase 2 dose of the intra-patient dose escalation regimen.
Drug: IMCgp100
Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3
Other Names:
  • Tebentafusp
  • Kimmtrak




Primary Outcome Measures :
  1. Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1 [ Time Frame: Up to 49 months ]
    Number of participants with a dose limiting toxicity, defined as an adverse event (AE) or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment and meets any of the pre-specified criteria.

  2. Objective Response Rate in Phase 2 [ Time Frame: Up to 38 months ]
    Objective response rate (ORR) is defined as the percentage of participants with measurable disease with at least 1 visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an independent central review (ICR). The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.


Secondary Outcome Measures :
  1. Objective Response Rate in Phase 1 [ Time Frame: Up to 49 months ]
    ORR is defined as the percentage of participants with measurable disease with at least 1 visit response of CR or PR that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an investigator. The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.

  2. Progression-free Survival [ Time Frame: Up to 49 months ]
    Progression-free survival is defined as the time in months from first dose of study drug until the date of disease progression or death (by any cause in the absence of disease progression) as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.

  3. Disease Control Rate [ Time Frame: 24 weeks ]
    Disease control rate (DCR) is defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD) recorded at least 24 weeks (± 1 week) after commencement of study drug and prior to any progressive disease (PD) event, as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.

  4. Duration of Response [ Time Frame: Up to 49 months ]
    Duration of response (DOR) is defined as the time in months from the date of first documented objective response (CR or PR) until the date of documented disease progression or death by any cause in the absence of disease progression as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.

  5. Time to Response [ Time Frame: Up to 49 months ]
    Time to response (TTR) is defined as the time in months from the date of first dose of study drug until the date of first documented objective response as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.

  6. Overall Survival [ Time Frame: Up to 49 months ]
    Overall survival (OS) is defined as the time in months from the date of first dose of study drug until death due to any cause in general.

  7. Minor Response Rate [ Time Frame: Up to 49 months ]
    Rate of minor response (or better) is defined as the proportion of participants with a confirmed CR, PR, or minor response (MinR) as assessed by RECIST v1.1 by the investigator for Phase 1 or ICR for Phase 2, where MinR is a reduction from baseline in sum of diameters between 10%-29%. The sum of diameters is defined as per RECIST v1.1 as the sum of longest diameters or short axis of target lesions (mm).

  8. Number of Participants With Treatment Dose Interruptions or Reductions [ Time Frame: Up to 49 months ]
    Tolerability of study treatment was assessed by summarizing the number of participants with dose interruptions or reductions that occurred during the treatment period.

  9. Pharmacokinetic Parameter AUC [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) ]
    Area under the plasma concentration-time curve (AUC) in dose escalation cohorts

  10. Pharmacokinetic Parameter Cmax [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) ]
    The maximum observed plasma drug concentration after single dose administration in dose escalation cohorts

  11. Pharmacokinetic Parameter Tmax [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) ]
    The time to reach maximum plasma concentration in dose escalation cohorts

  12. Pharmacokinetic Parameter t1/2 [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) ]
    Elimination half-life in dose escalation cohorts

  13. Percentage of Participants With Anti-IMCgp100 Antibody Formation [ Time Frame: Up to 49 months ]
    Overall antidrug antibody (ADA) is presented as number of ADA-positive participants relative to total number of participants with evaluable ADA results in each cohort



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participants age ≥ 18 years of age at the time of informed consent.
  2. Ability to provide and understand written informed consent prior to any study procedures.
  3. Histologically or cytologically confirmed diagnosis of metastatic uveal melanoma (mUM).
  4. Surgically sterile participants or participants of child-bearing potential who agree to use highly effective methods of contraception during study dosing and for 6 months after last dose of study drug.
  5. Human leukocyte antigen (HLA)-A*0201 positive.
  6. ECOG Performance Status of 0 or 1 at Screening.
  7. Phase 2 will include participants with previously treated uveal melanoma in the metastatic setting.

Exclusion Criteria:

  1. Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids.
  2. History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies.
  3. Participants with any out-of-range laboratory values.
  4. Clinically significant cardiac disease or impaired cardiac function.
  5. Active infection requiring systemic antibiotic therapy.
  6. Known history of HIV infection.
  7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol.
  8. Participants receiving systemic treatment with systemic steroid therapy or any other immunosuppressive medication at any dose level that would interfere with the action of the study drugs in the opinion of the investigator.
  9. Malignant disease, other than that being treated in this study.
  10. Any medical condition that would, in the investigator's judgment, prevent participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results.
  11. Presence of NCI CTCAE ≥ grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ NCI CTCAE grade 3) due to prior cancer therapy.
  12. Pregnant, likely to become pregnant, or lactating women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02570308


Locations
Show Show 26 study locations
Sponsors and Collaborators
Immunocore Ltd
  Study Documents (Full-Text)

Documents provided by Immunocore Ltd:
Study Protocol  [PDF] November 26, 2018
Statistical Analysis Plan  [PDF] May 28, 2020

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Responsible Party: Immunocore Ltd
ClinicalTrials.gov Identifier: NCT02570308    
Other Study ID Numbers: IMCgp100-102
First Posted: October 7, 2015    Key Record Dates
Results First Posted: September 1, 2021
Last Update Posted: March 21, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Immunocore Ltd:
Tebentafusp
IMCgp100
gp100
metastatic melanoma
ImmTAC
Immunotherapy
Bispecific T cell receptor fusion protein
Immune mobilizing monoclonal T cell receptor
against cancer
UM
mUM
Kimmtrak
Additional relevant MeSH terms:
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Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases