Select Advanced Solid Tumors
Conditions
Keywords
ImmTAC, IMC-C103C, MAGE-A4, immunotherapy
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.
Interventions
DRUGIMC-C103C
Weekly IV infusions
DRUGAtezolizumab
IV infusions every 3 weeks
Sponsors
Immunocore Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Sequential from arm monotherapy IV dose escalation is opened first; then monotherapy SC dose escalation, monotherapy expansion and combination dose escalation may run
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 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 | — |
| 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) | — |
| 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 | — |
Countries
Spain, United Kingdom, United States
Outcome results
None listed