First in Human Study of TORL-4-500 in Participants With Advanced Cancer

Study Overview
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Brief Summary
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This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-4-500 in patients with advanced cancer

Official Title
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A Phase 1, First in Human, Dose-Escalation Study of TORL-4-500 in Participants With Advanced Cancer

Conditions
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Advanced Solid Tumor, Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: TORL-4-500


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced solid tumor Measurable disease, per RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Adequate organ function Exclusion Criteria: Has not recovered [recovery is defined as NCI CTCAE, version 5.0, grade ≤1] from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements Received prior chemotherapeutic, investigational, or other therapies for the treatment of cancer within 14 days with small molecule and within 28 days with biologic before the first dose of TORL-4-500 Progressive or symptomatic brain metastases Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection History of significant cardiac disease History of myelodysplastic syndrome (MDS) or AML History of another cancer within 3 years before Day 1 of study treatment, with the exception of basal or squamous cell carcinoma of the skin that has been definitively treated. A history of other malignancies with a low risk of recurrence, including appropriately treated ductal carcinoma in situ (DCIS) of the breast and prostate cancer with a Gleason score less than or equal to 6, are also not excluded If female, is pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy Dose Dose Finding - Part 1<br>TORL-4-500 iv once every 3 weeks | Drug: TORL-4-500<br>* antibody drug conjugate<br>|
| Experimental: Expansion as Monotherapy - Part 2<br>TORL-4-500 iv once every 3 weeks | Drug: TORL-4-500<br>* antibody drug conjugate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events and serious adverse events | Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE Version 5.0 | up to 2 years | 
| Maximum Tolerated Dose (MTD) | Highest administered dose with < 33% participants experiencing dose limiting toxicity (DLT) in the first 6 DLT evaluable participants | 28 Days | 
| Recommended Phase 2 Dose (RP2D) | Based on the maximum tolerated dose, cumulative safety, and pharmacokinetic data | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Percentage of participants with best response of complete response (CR) or partial response (PR) according to RECIST 1.1 | up to 2 years | 
| Duration of Response (DOR) | Time from CR or PR to objective disease progression or death to any cause | up to 2 years | 
| Progression Free Survival (PFS) | PFS is defined as the time from the start of the treatment until objective disease progression or death from any cause | up to 2 years | 
| Time to Response (TTR) | Time from start of treatment to complete response or partial response | up to 2 years | 
| 1 Year Overall Survival (1YOS) | Proportion of participants alive at 1 year from the start of treatment to death from any cause | 1 year | 
| 2 Year Overall Survival (2YOS) | Proportion of participants alive at 2 years from the start of treatment to death from any cause | 2 years | 
| Number of anti-drug antibody (ADA) Positive Participants | Immunogenicity will be measured by the number of participants that are ADA positive. | up to 2 years | 
| Maximum Serum Concentration of TORL-4-500 (Cmax) | PK assessment | 21 days | 
| Minimum Serum Concentration of TORL-4-500 (Cmin) | PK assessment | 21 days | 
| Maximum Serum Concentration of TORL-4-500 at Steady State (Cmax,ss) | PK assessment | 63 days | 
| Minimum Serum Concentration of TORL-4-500 at Steady State (Cmin,ss) | PK assessment | 63 days | 
| Time of Maximum Serum Concentration of TORL-4-500 (Tmax) | PK assessment | 21 days | 
| Time of Minimum Serum Concentration of TORL-4-500 (Tmin) | PK Assessment | 21 days | 
| Time of Minimum Serum Concentration of TORL-4-500 at Steady State (Tmin,ss) | PK Assessment | 63 days | 
| Terminal Half-life (t1/2) of Serum TORL-4-500-ADC | PK Assessment | 63 days | 
| Area under the Serum Concentration-Time curve from the time of dosing to the last measurable concentration (AUClast) for TORL-1-23 | PK Assessment | 21 days | 
| Area under the Serum Concentration-Time curve from the time of dosing extrapolated to time infinity (AUCinf) for TORL-1-23 | PK Assessment | 63 days | 
| Apparent volume of distribution during the terminal phase (Vz) of TORL-4-500 | PK Assessment | 63 days | 
| Clearance (CL) of TORL-4-500 | PK Assessment | 63 days | 
| Accumulation ratio (Rac) of TORL-4-500 | PK Assessment | 63 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADC