Clinical trial NCT03515551: Safety and Efficacy of IMCnyeso in Advanced NY-ESO-1 and/or LAGE-1A Positive Cancers
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Select Advanced Solid Tumors
Keywords: IMCnyeso
Immunotherapy
Lead sponsor: Immunocore Ltd
Sponsor class: INDUSTRY
First posted: 2018-05-03
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Number of Participants With Dose-limiting Toxicities
timeFrame: Up to 35 months
measure: Phase 1: Number of Participants With Adverse Events
timeFrame: Up to 35 months
measure: Phase 1: Number of Participants With No Dose Interruptions or Reductions
timeFrame: Up to 35 months
measure: Phase 2: Best Overall Response (BOR)
timeFrame: Up to 35 months
Secondary outcomes:
measure: Phase 2: Number of Participants With Adverse Events
timeFrame: Up to 35 months
measure: Phase 2: Number of Participants With No Dose Interruptions or Reductions
timeFrame: Up to 35 months
measure: Phase 1: Number of Participants With Best Overall Response (BOR)
timeFrame: Up to 35 months
measure: Phase 1 and Phase 2: Progression-free Survival
timeFrame: Up to 35 months
measure: Phase 1 and Phase 2: Duration of Response
timeFrame: Up to 35 months
measure: Phase 1 and Phase 2: Overall Survival
timeFrame: Up to 35 months
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last)
timeFrame: Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15
measure: Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax)
timeFrame: Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15
measure: Time to Reach Maximum Plasma Concentration (Tmax)
timeFrame: Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15
measure: Number of Participants With Anti-IMCnyeso Antibody Formation
timeFrame: Up to 35 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC - Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology NASH - SCRI
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Immunocore Ltd
name: Study Director
role: STUDY_DIRECTOR
References: