Clinical Trials /

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

NCT03515551

Description:

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.

Related Conditions:
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Synovial Sarcoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: IMCnyeso-101
  • NCT ID: NCT03515551

Conditions

  • Melanoma
  • Advanced NSCLC
  • Urothelial Carcinoma
  • Synovial Sarcoma

Interventions

DrugSynonymsArms
IMCnyesoIMCnyeso dose Escalation Phase (Arm 1)
IMCnyesoIMCnyeso expansion phase (Arm 2)

Purpose

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.

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
    

Trial Arms

NameTypeDescriptionInterventions
IMCnyeso dose Escalation Phase (Arm 1)ExperimentalPhase (Arm 1) n=up to 33 Melanoma, NSCLC, urothelial carcinoma and synovial sarcoma patients to establish the MTD/RP2D
  • IMCnyeso
IMCnyeso expansion phase (Arm 2)ExperimentalPatients 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
  • IMCnyeso

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended phase 2 dose (RP2D)
Time Frame:From day 1 to day 28 of treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Pharmacokinetics
Time Frame:2 weeks (AUC will be assessed weekly for 2 weeks)
Safety Issue:
Description:Area under the plasma concentration-time curve (AUC)
Measure:Pharmacokinetics
Time Frame:Up to 2 years
Safety Issue:
Description:The maximum observed plasma drug concentration after single dose administration (Cmax)
Measure:Pharmacokinetics
Time Frame:Up to 2 years
Safety Issue:
Description:The time to reach maximum plasma concentration (Tmax)
Measure:Pharmacokinetics
Time Frame:2 weeks (t1/2 will be assessed after the first two doses of IMCnyeso, an average of 2 weeks)
Safety Issue:
Description:The elimination half-life (t1/2)
Measure:Pharmacokinetics
Time Frame:up to 2 years
Safety Issue:
Description:The incidence of anti-IMCnyeso antibody formation

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Immunocore Ltd

Trial Keywords

  • Melanoma
  • Lung Cancer
  • Bladder Cancer
  • Sarcoma
  • IMCnyeso
  • Immunotherapy

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