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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Select Advanced Solid Tumors

Intervention / Treatment
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* Drug: IMCnyeso


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HLA-A*0201 positive NY-ESO-1 and/or LAGE-1A positive tumor ECOG PS 0 or 1 Selected advanced solid tumors Relapsed from, refractory to, or intolerant of standard therapy If applicable, must agree to use highly effective contraception Exclusion Criteria: Symptomatic or untreated central nervous system metastasis Inadequate washout from prior anticancer therapy Significant ongoing toxicity from prior anticancer treatment Impaired baseline organ function as evaluated by out-of-range laboratory values Clinically significant cardiac disease Active infection requiring systemic antibiotic therapy Known history of human immunodeficiency virus (HIV) Active hepatitis B virus (HBV) or hepatitis C virus (HCV) Ongoing treatment with systemic steroids or other immunosuppressive therapies Significant secondary malignancy Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Dose Escalation<br>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<br>* Weekly IV infusions of IMCnyeso<br>|
| Experimental: Phase 2: Dose Expansion<br>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<br>* Weekly IV infusions of IMCnyeso<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IMCnyeso, Immunotherapy