NCT07423117 - A Study of ITC-6146RO in Patients With Advanced or Metastatic Cancer Who Have Failed Standard Therapy | Crick | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Phase 1a (Dose Escalation) Incidence of Adverse Events (AEs)

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, (%)

Time frame: Through study completion (Up to 2 years)

Phase 1b (Dose Expansion) Incidence of AEs

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, %

Time frame: Through study completion (Up to 2 years)

Secondary Outcomes

Phase 1a (Dose Escalation) Maximum Tolerated Dose (MTD) or Optimal Biological Dose (OBD) of ITC-6146RO

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).

Time frame: Through study completion (Up to 2 years)

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

Plasma AUClast following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Single-Dose Administration of ITC-6146RO

Plasma AUCinf following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Maximum Observed Plasma Concentration (Cmax) After Single-Dose Administration of ITC-6146RO

Plasma Cmax following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Terminal Elimination Half-life (t1/2) After Single-Dose Administration of ITC-6146RO

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.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Time to Maximum Observed Plasma Concentration (Tmax) After Single-Dose Administration of ITC-6146RO

Plasma Tmax following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Apparent Clearance (CL) After Single-Dose Administration of ITC-6146RO

Plasma apparent clearance (CL) following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Apparent Volume of Distribution (Vz) After Single-Dose Administration of ITC-6146RO

Plasma apparent volume of distribution (Vz) following a single dose of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

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

Plasma AUClast following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Maximum Observed Plasma Concentration at Steady State (Cmax,ss) After Multiple-Dose Administration of ITC-6146RO

Plasma Cmax,ss (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Trough Plasma Concentration at Steady State (Ctrough,ss) After Multiple-Dose Administration of ITC-6146RO

Plasma Ctrough,ss (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Average Plasma Concentration Over the Dosing Interval at Steady State (Cav,τ) After Multiple-Dose Administration of ITC-6146RO

Plasma Cav,τ (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Terminal Elimination Half-life at Steady State (t1/2,ss) After Multiple-Dose Administration of ITC-6146RO

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.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) After Multiple-Dose Administration of ITC-6146RO

Plasma Tmax,ss (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Apparent Clearance at Steady State (CLss) After Multiple-Dose Administration of ITC-6146RO

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.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Apparent Volume of Distribution at Steady State (Vss) After Multiple-Dose Administration of ITC-6146RO

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.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Accumulation Ratio After Multiple-Dose Administration of ITC-6146RO

Accumulation ratio (as applicable) following multiple-dose administration of ITC-6146RO will be calculated from plasma concentration-time data and summarized descriptively.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Peak-to-Trough Fluctuation (PTF) After Multiple-Dose Administration of ITC-6146RO

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.

Time frame: Through study completion (Up to 2 years)

Phase 1a (Dose Escalation) Incidence of Anti-Drug Antibodies (ADAs) to ITC-6146RO

Percentage of participants with detectable ADAs to ITC-6146RO (ADA-positive) based on a validated immunoassay.

Time frame: Through study completion (Up to 2 years)

Phase 1b (Dose Expansion) Population Pharmacokinetic (PopPK) Parameters of ITC-6146RO

PopPK parameters (e.g.,clearance and volume of distribution) will be estimated using PopPK modeling based on measured ITC-6146RO concentrations.

Time frame: Through study completion (Up to 2 years)

Phase 1b (Dose Expansion) Incidence of Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) to ITC-6146RO

Percentage of participants with detectable ADAs, including NAbs, to ITC-6146RO, as determined by validated immunoassay and neutralization assays (as applicable).

Time frame: Through study completion (Up to 2 years)

Phase 1a/b (Dose Escalation, Dose Expansion) Objective Response Rate (ORR) by Investigator per RECIST v1.1

ORR will be assessed by the investigator per RECIST v1.1

Time frame: Through study completion (Up to 2 years)

Phase 1a/b (Dose Escalation, Dose Expansion) Duration of Response (DoR) by Investigator per RECIST v1.1

DoR will be assessed by the investigator per RECIST v1.1

Time frame: Through study completion (Up to 2 years)

Phase 1a/b (Dose Escalation, Dose Expansion) Time to Response (TTR) by Investigator per RECIST v1.1

TTR will be assessed by the investigator per RECIST v1.1

Time frame: Through study completion (Up to 2 years)

Phase 1a/b (Dose Escalation, Dose Expansion) Progression-Free Survival (PFS) by Investigator per RECIST v1.1

PFS will be assessed by the investigator per RECIST v1.1

Time frame: Through study completion (Up to 2 years)

NCT07423117 - A Study of ITC-6146RO in Patients With Advanced or Metastatic Cancer Who Have Failed Standard Therapy | Crick | Crick