Clinical Trial 19485

Cancer Type:
Interventions:IMCgp100

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Zeynep Eroglu

Overview

Study 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

Summary

This research study is investigating a drug (that is called IMCgp100) in participants with advanced uveal melanoma. This research study will test the study drug to assess the safety and tolerability of IMCgp100 and to see if IMCgp100 can make tumors stop growing (or shrink). Participants will receive a lower dose on the first two weeks and in the third week and beyond, participants will receive a higher dose of the study drug. The research study will look at how people's bodies respond to the study drug and what happens to the study drug as it moves through people's bodies.

Objective

Phase II Dose Expansion: The primary objective is to estimate the objective response rate by independent central review based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in patients with advanced UM who are treated with the RP2D of IMCgp100 in the RP2D-IE

Inclusion Criteria

  • Male or female patients 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 patients, or patients 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
  • Life expectancy of >3 months as estimated by the investigator
  • Human leukocyte antigen (HLA)-A2 positive
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening
  • Must have disease (measurable or non-measurable acceptable) according to Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1 criteria
  • Patients in Phase 2 expansion cohort A will have experienced disease progression with 1 systemic treatment containing a checkpoint inhibitor. Any prior liver directed therapy is acceptable.
  • Patients in Phase 2 expansion cohort B will have experienced disease progression with 1 or 2 prior lines of therapy, including up to 1 prior line of liver-directed therapy.

  • Exclusion Criteria

  • Symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids within the prior 3 weeks to Study Day 1. Asymptomatic and adequately treated CNS metastases are not exclusionary.
  • History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies
  • Any out-of-range laboratory values
  • Clinically significant cardiac disease or impaired cardiac function
  • Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy before Screening.
  • Known history of HIV infection. Testing for HIV status is not necessary unless clinically indicated.
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated or the patient has a history of HBV or HCV infection.
  • 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. Additional details may apply.
  • A medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results
  • Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic or immunotherapy agents that can present with major delayed toxicity (e.g., anti-CTLA-4), 4 weeks is indicated as washout period
  • 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
  • Chronic systemic corticosteroid use (i.e., prednisone > 10 mg QD or the equivalent); treatment for well-controlled and asymptomatic adrenal insufficiency is permitted, but replacement dosing is limited to prednisone ≤ 10 mg QD or the equivalent, and patients must have no history of adrenal crisis. Local steroid therapies (e.g., otic, ophthalmic, intra-articular or inhaled medications) are acceptable
  • Major surgery within 2 weeks of the first dose of study drug
  • Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass
  • Use of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GMCSF, M-CSF) ≤ 2 weeks prior to start of study drug. Must have completed therapy at least 2 weeks before screening period begins with any hematopoietic colony-stimulating growth factors. An erythroid stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and patient is not red blood cell transfusion dependent.
  • Pregnant, or likely to become pregnant
  • Adrenal insufficiency or patients currently requiring chronic, systemic corticosteroid therapy at any dose for longer than 2 weeks. Local steroid therapies (e g., otic, ophthalmic, intraarticular, or inhaled medications) are acceptable.
  • May not have been included in any prior IMCgp100 trial, regardless of treatment cohort.