Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as LV, SGN-LIV1A
ladiratuzumab vedotin · 2 trials · 4 indications
An adverse event (AE) was any untoward medical occurrence in a study participant administered a medicinal product and which did not necessarily have a causal relationship with the study treatment. SAEs was defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect and other medically significant events. TEAEs were defined as newly occurring (not present at baseline) or worsened after first dose of investigational product within 30 days after last dose date or within 90 days for SAE. AEs included SAEs and all non-SAEs.
An AE was any untoward medical occurrence in a study participant administered a medicinal product and which did not necessarily have a causal relationship with the study treatment. SAEs was defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect and other medically significant events. AEs included SAEs and all non-SAEs. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. AEs were defined as treatment emergent if they were newly occurring or worsened following study treatment. Relatedness to study drug was assessed by the investigator.
An AE was any untoward medical occurrence in a study participant administered a medicinal product and which did not necessarily have a causal relationship with the study treatment. AEs severities were graded using the NCI CTCAE v4.03; where Grade 1= mild AE, Grade 2= moderate AE, Grade 3= severe AE, and Grade 4= life-threatening consequences; urgent intervention indicated, Grade 5= indicated death related to AE.
In this outcome measure, number of participants with maximum post-baseline laboratory toxicity grade in any hematology parameter are reported. As per NCI-CTCAE v4.03: Grade 1= mild, Grade 2= moderate, Grade 3= severe, and Grade 4= life-threatening consequences; urgent intervention indicated; Grade 0 = within normal limits. Baseline was defined as most recent non-missing lab result before first dose. Hematology parameters evaluated: hemoglobin, leukocytes, lymphocytes, neutrophils and platelets.
In this outcome measure, number of participants with maximum post-baseline laboratory toxicity grade in any serum chemistry parameters are reported. As per NCI-CTCAE v4.03: Grade 1= mild, Grade 2= moderate, Grade 3= severe, and Grade 4= life-threatening consequences; urgent intervention indicated; Grade 0 = within normal limits. Baseline was defined as most recent non-missing lab result before first dose. Serum chemistry parameters evaluated: alanine aminotransferase, albumin, alkaline phosphatase, amylase, aspartate aminotransferase, bilirubin, calcium corrected for albumin, calcium- ionized, creatinine, gamma glutamyl transferase, glucose, lipase, phosphate, potassium, sodium and urate. In this outcome measure, only those grades as rows are reported which had at least one participant for at least 1 reporting group.
DLT : hematologic and/or non-hematologic AE specified in protocol that is considered related to SGN-LIV or the combination and cannot be attributed to pembrolizumab alone including: any clinically significant, non-hematologic AE\>= Grade 3 according to NCI CTCAE v4.03, Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia associated with clinically significant bleeding that required medical intervention, Grade 4 anemia unrelated to underlying disease, discontinuation during Cycle 1 due to treatment-related toxicity/ inability to receive all 3 doses of SGN-LIV (Days 1, 8, and 15) as participant not met dosing criteria (Part C only)prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity and Grade 5 event (death).
ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Kaplan Meier method was used for analysis.
An AE is any untoward medical occurrence in a patient or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
To be summarized using descriptive statistics.
| Arm | Type | Description |
|---|---|---|
| LV + pembrolizumab | EXPERIMENTAL | LV + pembrolizumab |
| LV Dose Escalation | EXPERIMENTAL | - |
| LV + Trastuzumab | EXPERIMENTAL | - |
| LV Monotherapy | EXPERIMENTAL | LV will be given at the recommended dose (at or below the monotherapy MTD determined in the LV dose escalation arm). |
| Name | Type | Description |
|---|---|---|
| ladiratuzumab vedotin | DRUG | Given into the vein (IV; intravenously) |
| Pembrolizumab | DRUG | IV infusion every 3 weeks |
| Trastuzumab | DRUG | Trastuzumab will be given by IV every 3 weeks at a dose of 6 mg/kg (the first dose will be 8 mg/kg) |
Inclusion Criteria: * Metastatic or locally-advanced, histologically documented TNBC (absence of HER2, ER, and PR expression) * Part D only: Tumor tissue PD-L1 Combined Positive Score \<10 expression. * Have not previously received cytotoxic therapy for the treatment of unresectable locally-adva...
Ladiratuzumab vedotin is an investigational antibody-drug conjugate being studied in breast cancer, including HER2 positive breast neoplasms and triple negative breast neoplasms. It has been evaluated in Phase 1 clinical trials in patients with locally advanced or metastatic disease. It is not an approved therapy.
Ladiratuzumab vedotin targets SLC39A6, also known as LIV-1, a protein expressed on breast cancer cells. The antibody portion binds this target, and the conjugated payload acts on tubulin subunits including TUBB4B, TUBB1, TUBA3C, TUBA4A and TUBB3, disrupting microtubules in targeted cells.
Ladiratuzumab vedotin is being developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. The agent was originally studied under the designation SGN-LIV1A before Pfizer's involvement in its development.
Ladiratuzumab vedotin is in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA for any indication. The Phase 1 studies evaluating it have been completed.
Ladiratuzumab vedotin has been studied in two completed Phase 1 trials. NCT03310957 evaluated it plus pembrolizumab in locally advanced or metastatic triple negative breast cancer across the United States, Germany, South Korea and Spain. NCT01969643 was a safety study in breast cancer patients, including HER2 positive, hormone receptor positive and triple negative disease.
Yes, ladiratuzumab vedotin is also known as SGN-LIV1A. The two names refer to the same antibody-drug conjugate, and clinical trial records for SGN-LIV1A describe the same agent now called ladiratuzumab vedotin.