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

NCT02570308 | Completed Phase 1 Results FDA Drug

• 1 other identifier: IMCgp100-102
• Study Type: interventional
• Target: 146
• Locations: 5 countries
• Sites: 26

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.

Conditions

Uveal Melanoma

Keywords

Tebentafusp; IMCgp100; gp100; metastatic melanoma; ImmTAC; Immunotherapy; Bispecific T cell receptor fusion protein; Immune mobilizing monoclonal T cell receptor; against cancer; UM; mUM; Kimmtrak

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1

  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.

  Up to 49 months

• Objective Response Rate in Phase 2

  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.

  Up to 38 months

Secondary Outcomes (13)

• Objective Response Rate in Phase 1

  Up to 49 months

• Progression-free Survival

  Up to 49 months

• Disease Control Rate

  24 weeks

• Duration of Response

  Up to 49 months

• Time to Response

  Up to 49 months

Study Arms (2)

Dose escalation

EXPERIMENTAL

Dose escalation cohorts of the intra-patient escalation regimen.

Drug: IMCgp100

Dose expansion

EXPERIMENTAL

Dose expansion cohort with the recommended phase 2 dose of the intra-patient dose escalation regimen.

Drug: IMCgp100

Interventions

IMCgp100 DRUG

Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3

Also known as: Tebentafusp, Kimmtrak

Dose escalation; Dose expansion

Eligibility Criteria

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

You may qualify if:

• Male or female participants age ≥ 18 years of age at the time of informed consent.
• Ability to provide and understand written informed consent prior to any study procedures.
• Histologically or cytologically confirmed diagnosis of metastatic uveal melanoma (mUM).
• 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.
• Human leukocyte antigen (HLA)-A\*0201 positive.
• ECOG Performance Status of 0 or 1 at Screening.
• Phase 2 will include participants with previously treated uveal melanoma in the metastatic setting.

You may not qualify if:

• Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids.
• History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies.
• Participants with any out-of-range laboratory values.
• Clinically significant cardiac disease or impaired cardiac function.
• Active infection requiring systemic antibiotic therapy.
• Known history of HIV infection.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol.
• 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.
• Malignant disease, other than that being treated in this study.
• 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.
• 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.
• Pregnant, likely to become pregnant, or lactating women.

Sponsors & Collaborators

• Immunocore Ltd: lead

Study Sites (26)

University California, San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

The Angeles Clinic and Research Institute - W LA Office

Los Angeles, California, 90025, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of Colorado Denver Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Georgetown University - Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Miami Hospital Clinics/Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, 33612-9497, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Washington University, School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University Medical Center - The New York Presbyterian Hospital

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Hospital

New York, New York, 10065, United States

Location

Dean A. Mcgee Eye Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Thomas Jefferson University Medical Oncology Clinic

Philadelphia, Pennsylvania, 19107, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor Scott & White Health

Temple, Texas, 76508, United States

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G2M9, Canada

Location

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, 12200, Germany

Location

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

The Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, Merseyside, CH63 4JY, United Kingdom

Location

Mount Vernon Cancer Centre

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

Related Publications (1)

• Carvajal RD, Butler MO, Shoushtari AN, Hassel JC, Ikeguchi A, Hernandez-Aya L, Nathan P, Hamid O, Piulats JM, Rioth M, Johnson DB, Luke JJ, Espinosa E, Leyvraz S, Collins L, Goodall HM, Ranade K, Holland C, Abdullah SE, Sacco JJ, Sato T. Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial. Nat Med. 2022 Nov;28(11):2364-2373. doi: 10.1038/s41591-022-02015-7. Epub 2022 Oct 13.

  PMID: 36229663 DERIVED

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

tebentafusp

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Nicola McKelvie
• Organization: Immunocore, Ltd

nicola.mckelvie@immunocore.com

484-534-5261

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 6, 2015
• First Posted: October 7, 2015
• Study Start: February 29, 2016
• Primary Completion: March 20, 2020
• Study Completion: October 17, 2022
• Last Updated: March 21, 2023
• Results First Posted: September 1, 2021

Record last verified: 2023-02

Locations

ES (4); US (17); GB (2); DE (2); CA (1)