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

Select Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03515551
• Other study ID #: IMCnyeso-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 15, 2018
• Est. completion date: May 10, 2021

Study information

• Verified date: March 2022
• Source: Immunocore Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: May 10, 2021
• Est. primary completion date: May 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Select Advanced Solid Tumors

Intervention

Drug:
• IMCnyeso
Weekly IV infusions of IMCnyeso

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United Kingdom	Sarah Cannon Research Institute UK	London
United Kingdom	The Christie Hospital	Manchester
United Kingdom	Royal Marsden Hospital	Sutton
United States	University of Colorado Hospital	Aurora	Colorado
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Tennessee Oncology NASH - SCRI	Nashville	Tennessee
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	Washington University School of Medicine in St. Louis	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Immunocore Ltd

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Phase 2: Best Overall Response (BOR)	Best overall response per RECIST v.1.1	Up to 35 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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