Advanced Solid Tumor
Conditions
Brief summary
PMC2129G12 is an investigational intratumorally administered messenger RNA-lipid nanoparticle (mRNA-LNP) immunotherapy designed to enable localized, transient expression of a humanized EpCAM-targeted CD3-engaging bispecific antibody together with the immunostimulatory cytokines to kill tumors by recruited immune T cells.
Detailed description
This Phase 1/2a, open-label study is designed to evaluate the safety and tolerability of PMC2129G12 encoding humanized EpCAM-targeted CD3-engaging bispecific antibody together with the immunostimulatory cytokines administered by intratumoral injection in patients with EpCAM-positive advanced malignant solid tumors. Secondary and exploratory objectives include characterization of pharmacokinetics, pharmacodynamic immune effects, and preliminary antitumor activity. The study will provide critical information to support further clinical development of PMC2129G12 as a novel intratumoral immunotherapy for patients with advanced epithelial cancers.
Interventions
GENETICmRNA-LNP
intratumoral mRNA-LNP administration
Sponsors
IntraAb, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years * Histologically or cytologically confirmed advanced or metastatic solid tumor refractory to standard therapy * EpCAM expression ≥2+ intensity in ≥50% of tumor cells by central IHC * At least one measurable lesion per RECIST v1.1 (≥2 cm) that is anatomically accessible for intratumoral injection * ECOG performance status 0-1 * Life expectancy ≥3 months * Adequate hematologic, hepatic, renal, and coagulation function * Willingness to use effective contraception
Exclusion criteria
* Prior EpCAM- or CD3-targeted therapy * Active autoimmune disease requiring systemic therapy * Uncontrolled infection or significant cardiovascular disease * Active or symptomatic CNS metastases requiring immediate local therapy. Patients with treated, stable CNS metastases may be eligible. * Ongoing ≥Grade 2 toxicity from prior anticancer therapy * Known hypersensitivity to study drug components * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-emergent adverse events (TEAEs) assessed by CTCAE v5. | From first dose through Day 28 (±3 days) | The number of participants experiencing treatment-emergent adverse events following intratumoral administration of PMC2129G12, graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
| Number of participants with dose-limiting toxicities (DLTs) | From first dose through Day 28 (±3 days) | The number of participants experiencing dose-limiting toxicities during the DLT evaluation period following intratumoral administration of PMC2129G12. |
| Maximum tolerated dose (MTD) of PMC2129G12 | Up to approximately 28 days | Determination of the maximum tolerated dose (MTD) of PMC2129G12 administered by intratumoral injection based on the incidence of dose-limiting toxicities. |
Countries
United States
Contacts
CONTACTLijun Wu, MD
CONTACTLijun Lijun, MD
STUDY_CHAIRLijun Wu, MD
IntraAb, Inc.
Outcome results
None listed