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

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

IMC-C103C is an immune mobilizing monoclonal 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.

Study Overview

• Status: Withdrawn
• Conditions: Select Advanced Solid Tumors
• Intervention / Treatment: Drug: IMC-C103C; Drug: IMC-C103C; Drug: Atezolizumab

Detailed Description

The IMC-C103C-101 Phase 1/2 study will be evaluated in patients with metastatic/unresectable tumors which include select Advanced Solid Tumors and will be conducted in two phases.

1. To identify the maximum tolerated dose (MTD) and/or expansion dose of IMC-C103C as a single agent administered intravenously (IV) and subcutaneously (SC) once weekly (Q1W) and administered Q1W in combination with once every 3 weeks (Q3W) atezolizumab.
2. To assess the preliminary anti-tumor activity of IMC-C103C in one or more selected indications, as a single agent administered Q1W.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz - PPDS
  • Madrid, Spain, 28027
    • Clinica Universidad Navarra
  • Pamplona, Spain, 31008
    • Clinica Universidad Navarra
• United Kingdom
  • Bebington, United Kingdom, CH634JY
    • The Clatterbridge Hospital Cancer Center
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 OYN
      • Beatson West of Scotland Cancer Centre
• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehenvise Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine & Biological Sciences
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Medical center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute at Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. HLA-A*02:01 positive
2. MAGE-A4 positive tumor
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) [ECOG PS] 0 or 1
4. Selected advanced solid tumors
5. Relapsed from, refractory to, or intolerant of standard therapy
6. Measurable disease per RECIST v1.1 (expansion)
7. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMC-C103C and atezolizumab dose escalation; n=approximately 12 patients to establish the MTD/expansion dose	Drug: IMC-C103C; Weekly IV infusions; Other Names: TECENTRIQ; Atezolizumab; Q3W; Drug: IMC-C103C; Weekly subcutaneous Injection; Drug: Atezolizumab; IV infusions every 3 weeks; Other Names: TECENTRIQ
Experimental: IMC-C103C - expansion; Patients will be enrolled n=9-24 per expansion cohort (up to 4 total): metastatic/unresectable tumors of interest patients treated at the expansion dose of IMC-C103C to assess preliminary anti-tumor efficacy	Drug: IMC-C103C; Weekly IV infusions; Other Names: TECENTRIQ; Atezolizumab; Q3W; Drug: IMC-C103C; Weekly subcutaneous Injection
Experimental: IMC-C103C monotherapy SC dose escalation; Patients will be enrolled n=9-12 to establish the MTD/expansion dose	Drug: IMC-C103C; Weekly IV infusions; Other Names: TECENTRIQ; Atezolizumab; Q3W; Drug: IMC-C103C; Weekly subcutaneous Injection
Experimental: IMC-C103C - Monotherapy IV dose escalation; n= approximately 50 patients to establish the MTD/expansion dose	Drug: IMC-C103C; Weekly IV infusions; Other Names: TECENTRIQ; Atezolizumab; Q3W; Drug: IMC-C103C; Weekly subcutaneous Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Best overall response (BOR)		from first dose to approximately 2 years
Phase 1: Incidence of dose-limiting toxicities (DLT)		From first dose to DLT period (28 days)
Phase 1: incidence and severity of adverse events (AE)		from first dose to 30 days after the last dose
Phase 1: changes in laboratory parameters	Abnormalities will be classified according to NCI CTCAE v5.0	from first dose to 30 days after the last dose
Phase 1: changes in vital signs	Abnormalities will be classified according to NCI CTCAE v5.0	from first dose to 30 days after the last dose
Phase 1: dose interruptions, reductions, and discontinuations		from first dose through last dose (anticipated for up to 12-24 months)
Phase 1: changes in electrocardiogram parameters	QT intervals corrected for heart rate using Fridericia's (cube root) correction (QTcF) interval absolute values and changes from baseline will be summarized	from first dose to 30 days after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		from first dose to approximately 2 years
Phase 2: incidence and severity of adverse events (AE)		from first dose to 30 days after the last dose
Phase 2: changes in laboratory parameters	Abnormalities will be classified according to NCI CTCAE v5.0	from first dose to 30 days after the last dose
Phase 2: changes in vital signs	Abnormalities will be classified according to NCI CTCAE v5.0	from first dose to 30 days after the last dose
Phase 2: changes in electrocardiogram parameters	QTcF interval absolute values and changes from baseline will be summarized	from first dose to 30 days after the last dose
Phase 2: dose interruptions, reductions, and discontinuations		from first dose through last dose (anticipated for up to 12-24 months)
Phase 1: Best overall response		from first dose to approximately 2 years
Progression-free survival		from first dose to approximately 2 years
Duration of response		from first dose to approximately 2 years
Pharmacokinetics Area under the plasma concentration-time curve (AUC)		from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks)
Pharmacokinetics The maximum observed plasma drug concentration after single dose administration (Cmax)		from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks)
Pharmacokinetics The time to reach maximum plasma concentration (Tmax)		from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks)
Pharmacokinetics The elimination half-life (t1/2)		from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks)
Immunogenicity the incidence of anti-drug antibody formation		from first dose to 14 days after the last dose
Changes in lymphocyte counts over time		from first dose to approx 4 weeks
Changes in serum cytokines over time		from first dose to approx.. 4wks
GCIG CA-125 response (ovarian carcinoma)		from first dose to approx.. 30 days after the last dose

Collaborators and Investigators

• Sponsor: Immunocore Ltd
• Investigators: Study Director: Mohammed Dar, MD, Immunocore Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): May 17, 2019
• Primary Completion (Estimated): September 25, 2023
• Study Completion (Estimated): September 25, 2023

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (Actual): June 4, 2019

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: ImmTAC, IMC-C103C, MAGE-A4, immunotherapy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: IMC-C103C-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No