Safety and Efficacy of IMC-C103C as Monotherapy and in Combination With Atezolizumab
- Conditions
- Select Advanced Solid Tumors
- Interventions
- Registration Number
- NCT03973333
- Lead Sponsor
- Immunocore Ltd
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- 75
- HLA-A*02:01 positive
- MAGE-A4 positive tumor
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) [ECOG PS] 0 or 1
- Selected advanced solid tumors
- Relapsed from, refractory to, or intolerant of standard therapy
- Measurable disease per RECIST v1.1 (expansion)
- If applicable, must agree to use highly effective contraception
- Symptomatic or untreated central nervous system metastasis
- Inadequate washout from prior anticancer therapy
- Significant ongoing toxicity from prior anticancer treatment
- Impaired baseline organ function as evaluated by out-of-range laboratory values
- Clinically significant cardiac disease
- Active infection requiring systemic antibiotic therapy
- Known history of human immunodeficiency virus (HIV)
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Ongoing treatment with systemic steroids or other immunosuppressive therapies
- Significant secondary malignancy
- Pregnancy or lactation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description IMC-C103C - Monotherapy IV dose escalation IMC-C103C n= approximately 50 patients to establish the MTD/expansion dose IMC-C103C and atezolizumab dose escalation IMC-C103C n=approximately 12 patients to establish the MTD/expansion dose IMC-C103C - expansion IMC-C103C 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 IMC-C103C monotherapy SC dose escalation IMC-C103C Patients will be enrolled n=9-12 to establish the MTD/expansion dose IMC-C103C and atezolizumab dose escalation Atezolizumab n=approximately 12 patients to establish the MTD/expansion dose
- Primary Outcome Measures
Name Time Method 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 from first dose to 30 days after the last dose Abnormalities will be classified according to NCI CTCAE v5.0
Phase 1: changes in vital signs from first dose to 30 days after the last dose Abnormalities will be classified according to NCI CTCAE v5.0
Phase 1: changes in electrocardiogram parameters from first dose to 30 days after the last dose QT intervals corrected for heart rate using Fridericia's (cube root) correction (QTcF) interval absolute values and changes from baseline will be summarized
Phase 1: dose interruptions, reductions, and discontinuations from first dose through last dose (anticipated for up to 12-24 months) Phase 2: Best overall response (BOR) from first dose to approximately 2 years
- Secondary Outcome Measures
Name Time Method Progression-free survival from first dose to approximately 2 years 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 Phase 2: incidence and severity of adverse events (AE) 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) Changes in lymphocyte counts over time from first dose to approx 4 weeks Phase 2: changes in laboratory parameters from first dose to 30 days after the last dose Abnormalities will be classified according to NCI CTCAE v5.0
Phase 2: changes in vital signs from first dose to 30 days after the last dose Abnormalities will be classified according to NCI CTCAE v5.0
Phase 2: changes in electrocardiogram parameters from first dose to 30 days after the last dose QTcF interval absolute values and changes from baseline will be summarized
Phase 1: Best overall response from first dose to approximately 2 years Duration of response from first dose to approximately 2 years Overall survival 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) 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
Trial Locations
- Locations (18)
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
The University of Chicago Medicine & Biological Sciences
🇺🇸Chicago, Illinois, United States
Oklahoma University Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
University of California Davis Comprehenvise Cancer Center
🇺🇸Sacramento, California, United States
UPMC Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Sarah Cannon Research Institute at Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Clinica Universidad Navarra
🇪🇸Pamplona, Spain
The Clatterbridge Hospital Cancer Center
🇬🇧Bebington, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Hospital Universitario La Paz - PPDS
🇪🇸Madrid, Spain
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Scotland, United Kingdom