Advanced Solid Tumor, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Pancreas Cancer
Conditions
Keywords
claudin18.2
Brief summary
This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-2-307-MAB in patients with advanced cancer
Interventions
DRUGTORL-2-307-MAB
monoclonal antibody
Sponsors
Translational Research in Oncology
TORL Biotherapeutics, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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-2-307-MAB * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events and serious adverse events | up to 2 years | Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE Version 5.0 |
| Maximum Tolerated Dose (MTD) | 28 Days | Highest administered dose with \< 33% participants experiencing dose limiting toxicity (DLT) in the first 6 DLT evaluable participants |
| Recommended Phase 2 Dose (RP2D) | up to 2 years | Based on the maximum tolerated dose, cumulative safety, and pharmacokinetic data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response (TTR) | up to 2 years | Time from start of treatment to complete response or partial response |
| 1 Year Overall Survival (1YOS) | 1 year | Proportion of participants alive at 1 year from the start of treatment to death from any cause |
| 2 Year Overall Survival (2YOS) | 2 years | Proportion of participants alive at 2 years from the start of treatment to death from any cause |
| Number of anti-drug antibody (ADA) Positive Participants | up to 2 years | Immunogenicity will be measured by the number of participants that are ADA positive. |
| Maximum Serum Concentration of TORL-2-307-MAB (Cmax) | 21 days | PK assessment |
| Minimum Serum Concentration of TORL-2-307-MAB (Cmin) | 21 days | PK assessment |
| Maximum Serum Concentration of TORL-2-307-MAB at Steady State (Cmax,ss) | 63 days | PK assessment |
| Minimum Serum Concentration of TORL-2-307-MAB at Steady State (Cmin,ss) | 63 days | PK assessment |
| Objective Response Rate (ORR) | up to 2 years | Percentage of participants with best response of complete response (CR) or partial response (PR) according to RECIST 1.1 |
| Time of Minimum Serum Concentration of TORL-2-307-MAB (Tmin) | 21 days | PK Assessment |
| Time of Minimum Serum Concentration of TORL-2-307-MAB at Steady State (Tmin,ss) | 63 days | PK Assessment |
| Terminal Half-life (t1/2) of Serum TORL-2-307-MAB | 63 days | PK Assessment |
| Area under the Serum Concentration-Time curve from the time of dosing to the last measurable concentration (AUClast) for TORL-2-307-MAB | 21 days | PK Assessment |
| Area under the Serum Concentration-Time curve from the time of dosing extrapolated to time infinity (AUCinf) for TORL-2-307-MAB | 63 days | PK Assessment |
| Apparent volume of distribution during the terminal phase (Vz) of TORL-2-307-MAB | 63 days | PK Assessment |
| Clearance (CL) of TORL-2-307-MAB | 63 days | PK Assessment |
| Accumulation ratio (Rac) of TORL-2-307-MAB | 63 days | PK Assessment |
| Time of Maximum Serum Concentration of TORL-2-307-MAB (Tmax) | 21 days | PK assessment |
| Duration of Response (DOR) | up to 2 years | Time from CR or PR to objective disease progression or death to any cause |
| Progression Free Survival (PFS) | up to 2 years | PFS is defined as the time from the start of the treatment until objective disease progression or death from any cause |
Countries
South Korea, United States
Outcome results
None listed