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

NCT ID: NCT02570308

Last Updated: 2023-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2022-10-17

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.

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.

Conditions

Uveal Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation

Dose escalation cohorts of the intra-patient escalation regimen.

Group Type: EXPERIMENTAL

IMCgp100

Intervention Type: DRUG

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

Dose expansion

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

Group Type: EXPERIMENTAL

IMCgp100

Intervention Type: DRUG

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

Interventions

IMCgp100

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

Intervention Type: DRUG

Other Intervention Names

Tebentafusp; Kimmtrak

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immunocore Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University California, San Diego Moores Cancer Center

La Jolla, California, United States

The Angeles Clinic and Research Institute - W LA Office

Los Angeles, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of Colorado Denver Anschutz Medical Campus

Aurora, Colorado, United States

Georgetown University - Lombardi Comprehensive Cancer Center

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

University of Miami Hospital Clinics/Sylvester Comprehensive Cancer Center

Miami, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

Washington University, School of Medicine

St Louis, Missouri, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Columbia University Medical Center - The New York Presbyterian Hospital

New York, New York, United States

Memorial Sloan Kettering Hospital

New York, New York, United States

Dean A. Mcgee Eye Institute

Oklahoma City, Oklahoma, United States

Providence Portland Medical Center

Portland, Oregon, United States

Thomas Jefferson University Medical Oncology Clinic

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor Scott & White Health

Temple, Texas, United States

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, , Germany

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital General Universitario de Valencia

Valencia, , Spain

The Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, Merseyside, United Kingdom

Mount Vernon Cancer Centre

Northwood, Middlesex, United Kingdom

Countries

United States; Canada; Germany; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36229663 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IMCgp100-102

Identifier Type: -

Identifier Source: org_study_id