Cancer, HLA-A*02:01-positive
Conditions
Brief summary
This phase 1/2 first-in-human study is designed to test the safety and efficacy of IMC-R117C (PIWIL1 × CD3 ImmTAC® Bispecific Protein) as a single agent and in combination with other therapies in HLA-A\*02:01-positive participants with selected advanced PIWIL1-Positive cancers.
Interventions
DRUGIMC-R117C
IV infusion
DRUGChemotherapy drug
IV infusion
DRUGKinase inhibitor
oral
DRUGAntiangiogenic Agent
IV infusion
IV infusion
Sponsors
Immunocore Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study will include sequential assignment for non-randomized and randomized arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 * HLA-A\*02:01-positive * Histologically confirmed advanced colorectal, esophageal, gastric, or ovarian carcinoma * Archived or fresh tumor tissue sample that must be confirmed as adequate * Evaluable/Measurable disease per RECIST 1.1 * Previously received applicable standard treatments * Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control
Exclusion criteria
* Symptomatic or untreated central nervous system metastasis * Recent bowel obstruction * Ongoing ascites or effusion requiring recent drainages * Significant ongoing toxicity from prior anticancer treatment * Out-of-range laboratory values * Clinically significant lung, heart, or autoimmune disease * Ongoing requirement for immunosuppressive treatment * Significant secondary malignancy * Hypersensitivity to study drug or excipients * Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Escalation: Percentage of participants with ≥1 dose-limiting toxicity (DLT) | Up to ~24 months |
| Dose Escalation: Percentage of participants with ≥1 adverse event (AE) | Up to ~24 months |
| Dose Escalation: Percentage of participants with ≥1 serious adverse event (SAE) | Up to ~24 months |
| Dose Escalation: Percentage of participants with significant changes in electrocardiogram (ECG) recordings | Up to ~24 months |
| Dose Escalation: Percentage of participants with significant changes in vital signs | Up to ~24 months |
| Dose Escalation: Percentage of participants with significant changes in laboratory results | Up to ~24 months |
| Dose Escalation: Percentage of participants with a dose interruption, reduction, or discontinuation | Up to ~24 months |
| Expansion: Best Overall Response (BOR) as Determined by RECIST v1.1 | Up to ~24 months |
Secondary
| Measure | Time frame |
|---|---|
| Dose Escalation: Best Overall Response (BOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination | Up to ~36 months |
| Dose Escalation: Duration of Response (DOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination | Up to ~36 months |
| Dose Escalation: Progression-free survival (PFS) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination | Up to ~36 months |
| Dose Escalation: Overall Survival (OS) with IMC-R117C Monotherapy and in Combination | Up to ~36 months |
| Expansion: Duration of Response (DOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy | Up to ~36 months |
| Expansion: Progression-free survival (PFS) as Determined by RECIST v1.1 with IMC-R117C Monotherapy | Up to ~36 months |
| Expansion: Overall Survival (OS) with IMC-R117C Monotherapy | Up to ~36 months |
| Expansion: Percentage of participants with ≥1 Adverse Events (AE) | Up to ~24 months |
| Expansion: Percentage of participants with ≥1 Serious Adverse Events (SAE) | Up to ~24 months |
| Expansion: Percentage of participants with significant changes in electrocardiogram (ECG) recordings | Up to ~24 months |
| Expansion: Percentage of participants with significant changes in vital signs | Up to ~24 months |
| Expansion: Percentage of participants with significant changes in laboratory findings | Up to ~24 months |
| Expansion: Percentage of participants with dose interruptions, reductions, or discontinuation | Up to ~24 months |
| All Study: Plasma Concentration of IMC-R117C | Up to ~36 months |
| All Study: Incidence of anti-IMC-R117C Antibody Formation | Up to ~36 months |
| All Study: Incidence of tumor expression and localization of PIWIL1 | Up to ~36 months |
Countries
Australia, Belgium, Germany, Italy, Netherlands, Spain
Contacts
CONTACTImmunocore Medical Information
CONTACTImmunocore Medical Information EU
Outcome results
None listed