Clinical Trials /

Safety and Efficacy of IMC-C103C as Monotherapy and in Combination With Atezolizumab

NCT03973333

Description:

IMC-C103C is an immune mobilizing T cell receptor against cancer (ImmTAC ®) designed for the treatment of cancers positive for the tumor-associated antigen MAGE-A4. This is a first-in-human trial designed to evaluate the safety and efficacy of IMC-C103C in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for MAGE-A4.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of IMC-C103C as Monotherapy and in Combination With Atezolizumab
  • Official Title: A Phase 1/2 First-in-human Study of the Safety and Efficacy of IMC-C103C as Single Agent and in Combination With Atezolizumab in HLA-A*0201-positive Patients With Advanced MAGE-A4-positive Cancer

Clinical Trial IDs

  • ORG STUDY ID: IMC-C103C-101
  • NCT ID: NCT03973333

Conditions

  • NSCLC
  • Esophageal Cancer
  • Gastric Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
IMC-C103CIMC-C103C - Arm A1
AtezolizumabIMC-C103C and atezolizumab Arm A2

Purpose

IMC-C103C is an immune mobilizing T cell receptor against cancer (ImmTAC) designed for the treatment of cancers positive for the tumor-associated antigen MAGE-A4. This is a first-in-human trial designed to evaluate the safety and efficacy of IMC-C103C in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for MAGE-A4.

Detailed Description

      The IMC-C103C-101 Phase 1/2 study will be evaluated in patients with metastatic/unresectable
      tumors of interest which include NSCLC, esophageal carcinoma, gastric carcinoma, HNSCC, and
      urothelial carcinoma and will be conducted in two phases.

        1. A Phase 1 dose escalation study to identify the MTD/RP2D of IMC-C103C as monotherapy
           (Arm A1) and IMC-C103C in combination with atezolizumab (Arm A2)

        2. A Phase 2 dose expansion cohort study to further characterize the safety and
           tolerability of IMC-C103C monotherapy (Arm B1) or in combination with atezolizumab (Arm
           B2).
    

Trial Arms

NameTypeDescriptionInterventions
IMC-C103C - Arm A1Experimentaln= approximately 35 NSCLC, esophageal carcinoma, gastric carcinoma, HNSCC, and urothelial carcinoma patients to establish the MTD/RP2D
  • IMC-C103C
IMC-C103C and atezolizumab Arm A2Experimentaln=approximately 21 NSCLC, esophageal carcinoma, gastric carcinoma, HNSCC, and urothelial carcinoma patients to establish the MTD/RP2D
  • IMC-C103C
  • Atezolizumab
IMC-C103C - Arm B1ExperimentalPatients will be enrolled n=20 metastatic/unresectable tumors of interest which include NSCLC, esophageal carcinoma, gastric carcinoma, HNSCC, and urothelial carcinoma patients treated at the RP2D of IMC-C103C characterize the safety and tolerability of IMC-C103C
  • IMC-C103C
IMC-C103C and atezolizumab Arm B2ExperimentalPatients will be enrolled n=20 metastatic/unresectable tumors of interest which include NSCLC, esophageal carcinoma, gastric carcinoma, HNSCC, and urothelial carcinoma patients treated at the RP2D of IMC-C103C characterize the safety and tolerability of IMC-C103C in combination with atezolizumab
  • IMC-C103C
  • Atezolizumab

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. MAGE-A4 positive tumor confirmed by the central laboratory

          4. Histologically confirmed diagnosis of metastatic/unresectable NSCLC, esophageal,
             gastric, urothelial, and HNSCC cancers are eligible

          5. Prior Treatments:

               -  Arms A1 and A2 — patients must be relapsed from, refractory to, or intolerant to
                  all approved classes of therapy for their disease. There is no limit on the
                  number of prior therapies

               -  Arms B1 and B2 — patients must have experienced disease progression or drug
                  intolerance in the unresectable/metastatic setting following at least one line of
                  chemotherapy AND one line of immune therapy as designated by the standard of care
                  for a particular disease. There is no limit on the number of prior therapies.

               -  Special consideration: NSCLC patients with known mutations (ie, EGFR, ROS, ALK,
                  B-Raf proto-oncogene serine/threonine kinase [BRAF]) must have experienced
                  disease progression or drug intolerance following at least one line of small
                  molecule targeted therapy and following platinum-based chemotherapy.

          6. Disease amenable to pre-treatment biopsy if no archival tissue available

          7. Measurable disease to RECIST v.1.1 criteria

        Exclusion Criteria:

          1. Impaired baseline organ function as evaluated by out-of-range laboratory values

          2. History of severe hypersensitivity reactions (eg, anaphylaxis) to 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:day 1 to day 21
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Immunocore Ltd

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