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

Phase 1

Terminated

• Conditions: Select Advanced Solid Tumors
• Interventions: Drug: IMCnyeso

• Registration Number: NCT03515551
• Lead Sponsor: Immunocore Ltd

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).

Study Timeline

• Study First Submitted: 2018-04-05
• Study First Submitted QC: 2018-05-02
• Study First Posted: 2018-05-03
• Study Start: 2018-06-15
• Primary Completion: 2021-05-10
• Study Completion: 2021-05-10
• Results First Submitted: 2021-12-08
• Status Verified: 2022-03
• Results First Submitted QC: 2022-03-09
• Last Update Submitted: 2022-03-09
• Results First Posted: 2022-03-11
• Last Update Posted: 2022-03-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 29

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 2: Dose Expansion	IMCnyeso	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.
Phase 1: Dose Escalation	IMCnyeso	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.

Primary Outcome Measures

Name	Time	Method
Phase 1: Number of Participants With Dose-limiting Toxicities	Up to 35 months	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
Phase 1: Number of Participants With Adverse Events	Up to 35 months	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.
Phase 2: Best Overall Response (BOR)	Up to 35 months	Best overall response per RECIST v.1.1
Phase 1: Number of Participants With No Dose Interruptions or Reductions	Up to 35 months	Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions

Secondary Outcome Measures

Name	Time	Method
Phase 2: Number of Participants With No Dose Interruptions or Reductions	Up to 35 months	Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions
Number of Participants With Anti-IMCnyeso Antibody Formation	Up to 35 months	Number of participants with positive treatment-boosted or treatment-induced anti-IMCnyeso antibody titers
Phase 1: Number of Participants With Best Overall Response (BOR)	Up to 35 months	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.
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
Phase 2: Number of Participants With Adverse Events	Up to 35 months	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.
Phase 1 and Phase 2: Progression-free Survival	Up to 35 months	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.
Phase 1 and Phase 2: Duration of Response	Up to 35 months	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.
Phase 1 and Phase 2: Overall Survival	Up to 35 months	Overall Survival is defined as the time (in months) from the date of randomization to the date of death due to any cause.
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

Trial Locations

Locations (12)

Washington University School of Medicine in St. Louis; 🇺🇸 Saint Louis, Missouri, United States

University of Iowa Hospital and Clinics; 🇺🇸 Iowa City, Iowa, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

UPMC - Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Tennessee Oncology NASH - SCRI; 🇺🇸 Nashville, Tennessee, United States

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Royal Marsden Hospital; 🇬🇧 Sutton, United Kingdom

Sarah Cannon Research Institute UK; 🇬🇧 London, United Kingdom

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

The Christie Hospital; 🇬🇧 Manchester, United Kingdom