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

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ClinicalTrials.gov Identifier: NCT03515551
Recruitment Status : Recruiting
First Posted : May 3, 2018
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd

Brief Summary:
IMCnyeso is a new biological therapy designed for the treatment of cancers which express NY-ESO-1 and/or LAGE-1A. This is a first-in-human trial designed to evaluate the safety and efficacy of IMCnyeso in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for NY-ESO-1 and/or LAGE-A1.

Condition or disease Intervention/treatment Phase
Melanoma Advanced NSCLC Urothelial Carcinoma Synovial Sarcoma Drug: IMCnyeso Phase 1 Phase 2

Detailed Description:
This is a multi-center, open label, dose finding Phase 1/2 study of single agent IMCnyeso administered in patients with NY-ESO-1 and/or LAGE-A1 positive tumors. The study consists of 2 Arms. In the first Arm (the dose escalation phase), IMCnyeso will be evaluated in 4 diseases (advanced non-small cell cancer (NSCLC), melanoma, urothelial carcinoma, and synovial sarcoma). The primary objective of this Arm is to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of IMCnyeso. The second Arm is an expansion phase in which the dose determined in Arm 1 will be tested in 3 diseases (advanced NSCLC, urothelial carcinoma and synovial sarcoma) to further evaluate the safety and assess the anti-tumor activity of IMCnyeso

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 1, 2018
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: IMCnyeso dose Escalation Phase (Arm 1)
Phase (Arm 1) n=up to 33 Melanoma, NSCLC, urothelial carcinoma and synovial sarcoma patients to establish the MTD/RP2D
Drug: IMCnyeso
Weekly IV infusions of IMCnyeso. The dose administered in each cohort will be determined following a review of the safety, PK and efficacy data and the dose will be guided by the Bayesian Logistic Regression Model, in order to determine the RP2D.

Experimental: IMCnyeso expansion phase (Arm 2)
Patients will be enrolled into 1 of 3 cohorts depending on disease type (NSCLC, urothelial carcinoma or synovial sarcoma) n=30 and treated at the RP2D of IMCnyso to determine the efficacy in these indications
Drug: IMCnyeso
Weekly IV infusions of IMCnyeso at the MTD or RP2D determined in Arm 1




Primary Outcome Measures :
  1. Recommended phase 2 dose (RP2D) [ Time Frame: From day 1 to day 28 of treatment ]
  2. Number of patients with treatment emergent AEs [ Time Frame: Safety will be assessed from informed consent through 90 days after end of treatment ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) defined as the proportion of patients achieving an objective response (RECIST v1.1 and modified irRECIST) (Arm 2 only) [ Time Frame: Up to 2 years ]
  2. Disease control rate (DCR) defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1 and modified irRECIST). (Part 2 only) [ Time Frame: Up to 2 years ]
  3. Pharmacokinetics [ Time Frame: 2 weeks (AUC will be assessed weekly for 2 weeks) ]
    Area under the plasma concentration-time curve (AUC)

  4. Pharmacokinetics [ Time Frame: Up to 2 years ]
    The maximum observed plasma drug concentration after single dose administration (Cmax)

  5. Pharmacokinetics [ Time Frame: Up to 2 years ]
    The time to reach maximum plasma concentration (Tmax)

  6. Pharmacokinetics [ Time Frame: 2 weeks (t1/2 will be assessed after the first two doses of IMCnyeso, an average of 2 weeks) ]
    The elimination half-life (t1/2)

  7. Pharmacokinetics [ Time Frame: up to 2 years ]
    The incidence of anti-IMCnyeso antibody formation



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients age ≥ 18 years of age at the time of informed consent
  2. HLA-A*0201 positive, confirmed by central laboratory
  3. NY-ESO-1 and/or LAGE-1A positive tumor confirmed by the central laboratory
  4. Arm 1: Patients must be refractory to or intolerant to all existing therapies known to provide clinical benefit for their condition.
  5. Arm 2: Subjects will have received the following previous therapies:

    1. NSCLC — PD-1/PD-L1 inhibitor
    2. Patients with NSCLC and an EGFR or ALK genomic tumor aberration must have disease progression after treatment with Health Authority-approved agents for these aberrations
    3. Urothelial cancer — PD-1/PD-L1 inhibitor
    4. Synovial sarcoma — at least one prior chemotherapy regimen
  6. Arm 1 only: Histologically confirmed diagnosis of advanced NSCLC, melanoma, urothelial carcinoma, or synovial sarcoma
  7. Arm 2 only: Histologically confirmed diagnosis of advanced NSCLC, urothelial carcinoma, or synovial sarcoma
  8. Arm 2 only: Disease amenable to biopsy
  9. Arm 2 only: Measurable disease to RECIST v.1.1 criteria

Exclusion Criteria:

Impaired baseline organ function as evaluated by out-of-range laboratory values 2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies 3. Clinically significant cardiac disease or impaired cardiac function 4. Presence of symptomatic or untreated central nervous system (CNS) metastases 5. Active infection requiring systemic antibiotic therapy 6. Known history of human immunodeficiency virus infection (HIV) 7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 8. Malignant disease, other than that being treated in this study 9. Patients receiving systemic steroid therapy or any other systemic immunosuppressive medication. Local steroid therapies are acceptable 10. Systemic anti-cancer therapy within 2 weeks of the first dose of study drug.

11. Major surgery within 2 weeks of the first dose of study drug 12. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field 13. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) ≤ 2 weeks prior to start of study drug 14. Pregnant, likely to become pregnant, or lactating women


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03515551


Contacts
Contact: Rachael Easton, MD, PhD 484-434-5261 rachael.easton@immunocore.com
Contact: Julia Hamlin +44 (0) 7921 468416 Julia.Hamlin@immunocore.com

Locations
United States, Pennsylvania
Thomas Jefferson University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Takami Sato, MD    215-955-8874      
Principal Investigator: Takami Sato, MD         
Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Hassane Zarour, MD    412-623-6121      
Principal Investigator: Hassane Zarour, MD         
United Kingdom
Royal Marsden Recruiting
Sutton, United Kingdom
Contact: Juanita Lopez, MD         
Contact    (0)2086613539      
Principal Investigator: Juanita Lopez, MD         
Sponsors and Collaborators
Immunocore Ltd

Responsible Party: Immunocore Ltd
ClinicalTrials.gov Identifier: NCT03515551     History of Changes
Other Study ID Numbers: IMCnyeso-101
First Posted: May 3, 2018    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Immunocore Ltd:
Melanoma
Lung Cancer
Bladder Cancer
Sarcoma
IMCnyeso
Immunotherapy

Additional relevant MeSH terms:
Melanoma
Sarcoma
Carcinoma, Transitional Cell
Sarcoma, Synovial
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Connective and Soft Tissue
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Connective Tissue