Safety and Efficacy of IMCnyeso in Advanced NY-ESO-1 and/or LAGE-1A Positive Cancers

A Phase I/II Study of IMCnyeso, HLA- A*0201-Restricted, NY-ESO-1- and LAGE-1A-specific Soluble T Cell Receptor and Anti-CD3 Bispecific Molecule, in HLA-A*0201 Positive Patients With Advanced NY-ESO-1 and/or LAGE - 1A Positive Cancer

IMCnyeso is a bispecific fusion protein designed for the treatment of cancers that express NY-ESO-1 and/or LAGE-1A. This was a first-in-human trial designed to evaluate the safety and efficacy of IMCnyeso in HLA-A*02:01-positive adult participants whose cancer is positive for NY-ESO-1 and/or LAGE-A1.

Study Overview

• Status: Terminated
• Conditions: Select Advanced Solid Tumors
• Intervention / Treatment: Drug: IMCnyeso

Detailed Description

This was planned to be a multi-center, open label, dose finding Phase 1/2 study of single agent IMCnyeso administered in participants with NY-ESO-1 and/or LAGE-A1 positive tumors. The primary objective of the dose escalation phase (Phase 1) was to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of IMCnyeso in participants with advanced solid tumors. Preliminary efficacy was to be evaluated in Phase 2. The study was terminated early (prior to initiation of Phase 2) by the Sponsor as a strategic decision (not based on any safety signal).

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • Sutton, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine in St. Louis
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC - Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology NASH - SCRI
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HLA-A*0201 positive
2. NY-ESO-1 and/or LAGE-1A positive tumor
3. ECOG PS 0 or 1
4. Selected advanced solid tumors
5. Relapsed from, refractory to, or intolerant of standard therapy
6. If applicable, must agree to use highly effective contraception

Exclusion Criteria:

1. Symptomatic or untreated central nervous system metastasis
2. Inadequate washout from prior anticancer therapy
3. Significant ongoing toxicity from prior anticancer treatment
4. Impaired baseline organ function as evaluated by out-of-range laboratory values
5. Clinically significant cardiac disease
6. Active infection requiring systemic antibiotic therapy
7. Known history of human immunodeficiency virus (HIV)
8. Active hepatitis B virus (HBV) or hepatitis C virus (HCV)
9. Ongoing treatment with systemic steroids or other immunosuppressive therapies
10. Significant secondary malignancy
11. Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Phase 1: Dose Escalation; Four fixed-dose, dose escalation cohorts (Cohorts 1 to 4) and 3 intrapatient dose escalation cohorts (Cohorts 5 to 7) to establish the MTD/RP2D of IMCnyeso.	Drug: IMCnyeso; Weekly IV infusions of IMCnyeso
EXPERIMENTAL: Phase 2: Dose Expansion; Three planned cohorts treated at the RP2D to make a preliminary assessment of the anti-tumor activity of IMCnyeso. Phase 2 was not initiated and data were not collected.	Drug: IMCnyeso; Weekly IV infusions of IMCnyeso

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Number of Participants With Dose-limiting Toxicities	Dose-limiting toxicities were defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug that occurs within the evaluation period, from the first dose up until Day 28 after the first dose	Up to 35 months
Phase 1: Number of Participants With Adverse Events	Treatment-emergent adverse events are defined as any adverse event (AE) that started after the first dose of study drug up to 30 days after last dose of study drug, including abnormal laboratory values, vital signs, or electrocardiogram results. AE severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.	Up to 35 months
Phase 1: Number of Participants With No Dose Interruptions or Reductions	Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions	Up to 35 months
Phase 2: Best Overall Response (BOR)	Best overall response per RECIST v.1.1	Up to 35 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Number of Participants With Adverse Events	Treatment-emergent adverse events are defined as any adverse event (AE) that started after the first dose of study drug up to 30 days after last dose of study drug, including abnormal laboratory values, vital signs, or electrocardiogram results.	Up to 35 months
Phase 2: Number of Participants With No Dose Interruptions or Reductions	Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions	Up to 35 months
Phase 1: Number of Participants With Best Overall Response (BOR)	Number of participants with best overall response, including complete response, partial response, stable disease, and progressive disease, based on local Investigator assessment as defined in RECIST v.1.1.	Up to 35 months
Phase 1 and Phase 2: Progression-free Survival	Progression-free survival is defined as the time from first dose until the date of objective progression, or death from any cause, whichever occurs first.	Up to 35 months
Phase 1 and Phase 2: Duration of Response	Duration of response is defined as the time from the date of first documented objective response (CR or PR) until the date of documented disease progression or death.	Up to 35 months
Phase 1 and Phase 2: Overall Survival	Overall Survival is defined as the time (in months) from the date of randomization to the date of death due to any cause.	Up to 35 months
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last)		Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15
Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax)		Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15
Time to Reach Maximum Plasma Concentration (Tmax)		Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15
Number of Participants With Anti-IMCnyeso Antibody Formation	Number of participants with positive treatment-boosted or treatment-induced anti-IMCnyeso antibody titers	Up to 35 months

Collaborators and Investigators

• Sponsor: Immunocore Ltd
• Investigators: Study Director: Study Director, Immunocore Ltd

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 15, 2018
• Primary Completion (ACTUAL): May 10, 2021
• Study Completion (ACTUAL): May 10, 2021

Study Registration Dates

• First Submitted: April 5, 2018
• First Submitted That Met QC Criteria: May 2, 2018
• First Posted (ACTUAL): May 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 11, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Immunotherapy; IMCnyeso
• Other Study ID Numbers: IMCnyeso-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No