Metastatic Castration-resistant Prostate Cancer, Metastatic Solid Tumor, Non-small Cell Lung Cancer, Triple Negative Breast Cancer
Conditions
Brief summary
The study consists of Phase 1a (dose escalation) and Phase 1b (dose expansion). In Phase 1a, sequential cohorts of subjects will receive escalating doses of ITC-6146RO to determine maximum tolerated dose (MTD) and/or optimal biological dose (OBD). In Phase 1b, the recommended phase 2 dose (RP2D) chosen from Phase 1a will be evaluated to further investigate safety, tolerability, pharmacokinetic (PK) and anti-tumor efficacy of ITC-6146RO.
Interventions
DRUGITC-6146RO
ITC-6146RO will be administered as an intravenous (IV) infusion at protocol-specified dose levels and schedules in Phase 1a (dose escalation) and Phase 1b (dose expansion).
Sponsors
IntoCell, Inc
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult males and females aged ≥ 19 years (Korea) or ≥ 18 years (United States) 2. Patients must be individuals who have voluntarily agreed to participate in the study after receiving a detailed explanation and fully understanding the nature of the clinical trial, and who have provided written informed consent. 3. Pathological confirmation of malignancy and evidence of metastatic or surgically unresectable disease 4. Patients must have at least one evaluable or measurable lesion based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST version 1.1). However, for patients with prostate cancer, eligibility will be determined based on Prostate Cancer Working Group 3 (PCWG3) 5. Patients who have received standard therapies and have no remaining clinically available approved treatment options. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 7. Estimated life expectancy of ≥ 3 months
Exclusion criteria
1. Inability to comply with study and follow-up procedures 2. Patients with a prior history of anticancer therapy before the first dose 3. History of another active malignancy within the past 3 years 4. Patients with central nervous system metastases, leptomeningeal disease, or spinal cord compression. 5. Patients who are currently participating in a clinical trial or have participated in a clinical trial involving a medical device or investigational product within 28 days prior to the first administration of ITC-6146RO 6. Has prior treatment with duocarmycin-containing agents 7. Pregnancy, lactation, or breastfeeding 8. Known Human immunodeficiency virus (HIV), Hepatitis C virus (HCV) and Hepatitis B virus (HBV) infection with active disease exception of the following conditions. 9. Tuberculosis with active disease 10. Active infection necessitating systemic therapy 11. Prior allogenic bone marrow transplantation or solid organ transplantation 12. History of autoimmune disease, treatment with systemic immunosuppressive medications 13. Patients with clinically significant pulmonary disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a (Dose Escalation) Incidence of Adverse Events (AEs) | Through study completion (Up to 2 years) | Grade 3 and 4 AEs, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Dose-limiting toxicities (DLTs) and AEs leading to discontinuation of study treatment, Evaluation of all-grade cardiac, renal, and pulmonary AEs , n, (%) |
| Phase 1b (Dose Expansion) Incidence of AEs | Through study completion (Up to 2 years) | Grade 3 and 4 AEs, TEAEs, SAEs and AEs leading to discontinuation of study treatment, Evaluation of all-grade cardiac, renal, and pulmonary AEs, n, % |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a (Dose Escalation) Maximum Tolerated Dose (MTD) or Optimal Biological Dose (OBD) of ITC-6146RO | Through study completion (Up to 2 years) | MTD/OBD will be reported as the final selected dose level for further investigation from Phase 1a dose escalation. MTD is determined by DLTs observed during the prespecified DLT observation period, and OBD is determined by meeting prespecified biological activity criteria (as defined in the protocol). |
| Phase 1a (Dose Escalation) Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) After Single-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma AUClast following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Single-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma AUCinf following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Maximum Observed Plasma Concentration (Cmax) After Single-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma Cmax following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Terminal Elimination Half-life (t1/2) After Single-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma terminal elimination half-life (t1/2) following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Time to Maximum Observed Plasma Concentration (Tmax) After Single-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma Tmax following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Apparent Clearance (CL) After Single-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma apparent clearance (CL) following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Apparent Volume of Distribution (Vz) After Single-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma apparent volume of distribution (Vz) following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma AUClast following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Maximum Observed Plasma Concentration at Steady State (Cmax,ss) After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma Cmax,ss (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Trough Plasma Concentration at Steady State (Ctrough,ss) After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma Ctrough,ss (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Average Plasma Concentration Over the Dosing Interval at Steady State (Cav,τ) After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma Cav,τ (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Terminal Elimination Half-life at Steady State (t1/2,ss) After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma terminal elimination half-life at steady state (t1/2,ss) (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma Tmax,ss (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Apparent Clearance at Steady State (CLss) After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma apparent clearance at steady state (CLss) (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Apparent Volume of Distribution at Steady State (Vss) After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Plasma apparent volume of distribution at steady state (Vss) (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Accumulation Ratio After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Accumulation ratio (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Peak-to-Trough Fluctuation (PTF) After Multiple-Dose Administration of ITC-6146RO | Through study completion (Up to 2 years) | Peak-to-trough fluctuation (PTF) (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively. |
| Phase 1a (Dose Escalation) Incidence of Anti-Drug Antibodies (ADAs) to ITC-6146RO | Through study completion (Up to 2 years) | Percentage of participants with detectable ADAs to ITC-6146RO (ADA-positive) based on a validated immunoassay. |
| Phase 1b (Dose Expansion) Population Pharmacokinetic (PopPK) Parameters of ITC-6146RO | Through study completion (Up to 2 years) | PopPK parameters (e.g.,clearance and volume of distribution) will be estimated using PopPK modeling based on measured ITC-6146RO concentrations. |
| Phase 1b (Dose Expansion) Incidence of Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) to ITC-6146RO | Through study completion (Up to 2 years) | Percentage of participants with detectable ADAs, including NAbs, to ITC-6146RO, as determined by validated immunoassay and neutralization assays (as applicable). |
| Phase 1a/b (Dose Escalation, Dose Expansion) Objective Response Rate (ORR) by Investigator per RECIST v1.1 | Through study completion (Up to 2 years) | ORR will be assessed by the investigator per RECIST v1.1 |
| Phase 1a/b (Dose Escalation, Dose Expansion) Duration of Response (DoR) by Investigator per RECIST v1.1 | Through study completion (Up to 2 years) | DoR will be assessed by the investigator per RECIST v1.1 |
| Phase 1a/b (Dose Escalation, Dose Expansion) Time to Response (TTR) by Investigator per RECIST v1.1 | Through study completion (Up to 2 years) | TTR will be assessed by the investigator per RECIST v1.1 |
| Phase 1a/b (Dose Escalation, Dose Expansion) Progression-Free Survival (PFS) by Investigator per RECIST v1.1 | Through study completion (Up to 2 years) | PFS will be assessed by the investigator per RECIST v1.1 |
Outcome results
None listed