C5741001

Seagen Inc.

21823 30th Drive S.E., Bothell, United States, 98021

Seagen Inc., Chief Medical Officer, 1 8554732436, medinfo@seagen.com

Seagen Inc., Chief Medical Officer, 1 8554732436, medinfo@seagen.com

No

No

No

Final

25 Mar 2025

No

Yes

30 Sep 2024

No

(i) To evaluate the safety and tolerability of the combination of ladiratuzumab vedotin (LV; SGN-LIV1A) and pembrolizumab in participants with locally-advanced or metastatic triple-negative breast cancer (LA/M TNBC) (ii)To identify the recommended dose and schedule of LV in combination with pembrolizumab in participants with LA/M TNBC (iii) To evaluate the confirmed objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 of the combination of LV and pembrolizumab in participants with LA/M TNBC.

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials participants were followed.

15 Mar 2018

Yes

Yes

Germany: 12

Korea, Republic of: 8

Spain: 45

United States: 120

185

57

0

0

0

0

0

0

141

44

0

Overall study (overall period)

Not applicable

Open-label study, no blinding was done.

Yes

Pembrolizumab

Solution for infusion

Infusion

200 mg was administered on Day 1 of each 21-day cycle as a 30-minute infusion.

SGN-LIV

Ladiratuzumab Vedotin, LV

Powder for solution for injection

Infusion

2.0 mg/kg was administered on Day 1 of every 21-day cycle by IV infusion given over approximately 30 minutes.

Pembrolizumab

Solution for infusion

Infusion

200 mg was administered on Day 1 of each 21-day cycle as a 30-minute infusion.

SGN-LIV

Ladiratuzumab Vedotin, LV

Powder for solution for injection

Infusion

2.5 mg/kg was administered on Day 1 of every 21-day cycle by IV infusion given over approximately 30 minutes.

Pembrolizumab

Solution for infusion

Infusion

200 mg was administered on Day 1, 8 and 15 of each 21-day cycle as a 30-minute infusion.

SGN-LIV

Ladiratuzumab Vedotin, LV

Powder for solution for injection

Infusion

1.0 mg/kg was administered on Day 1, 8 and 15 of every 21-day cycle by IV infusion given over approximately 30 minutes.

Pembrolizumab

Solution for infusion

Infusion

200 mg was administered on Day 1, 8 and 15 of each 21-day cycle as a 30-minute infusion.

SGN-LIV

Ladiratuzumab Vedotin, LV

Powder for solution for injection

Infusion

1.0 mg/kg was administered on Day 1, 8 and 15 of every 21-day cycle by IV infusion given over approximately 30 minutes.

Pembrolizumab

Solution for infusion

Infusion

200 mg was administered on Day 1, 8 of each 21-day cycle as a 30-minute infusion.

SGN-LIV

Ladiratuzumab Vedotin, LV

Powder for solution for injection

Infusion

1.5 mg/kg was administered on Day 1, 8 of every 21-day cycle by IV infusion given over approximately 30 minutes.

Part A, B: SGN-LIV 2.0 mg/kg (Q3WK) + Pembrolizumab

Part A, B: SGN-LIV 2.5 mg/kg (Q3WK) + Pembrolizumab

Part C: SGN-LIV 1.0 mg/kg (Q1WK) + Pembrolizumab

Part C: SGN-LIV 1.25 mg/kg (Q1WK) + Pembrolizumab

Part D: SGN-LIV 1.5 mg/kg (2Q3WK) + Pembrolizumab

Part A, B: SGN-LIV 2.0 mg/kg (Q3WK) + Pembrolizumab

Part A, B: SGN-LIV 2.5 mg/kg (Q3WK) + Pembrolizumab

Part C: SGN-LIV 1.0 mg/kg (Q1WK) + Pembrolizumab

Part C: SGN-LIV 1.25 mg/kg (Q1WK) + Pembrolizumab

Part D: SGN-LIV 1.5 mg/kg (2Q3WK) + Pembrolizumab

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. SAE 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. Safety analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab.

Primary

From start of study treatment up to 30 days after last dose for AEs and up to 90 days post last dose for SAEs (maximum exposure to any study intervention was 27 months; follow-up for AEs=maximum up to 28 months; follow-up for SAEs=maximum up to 30 months)

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. SAE 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. Relatedness to study drug was assessed by the investigator. Safety analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab.

Primary

From start of study treatment up to 30 days after last dose for AEs and up to 90 days post last dose for SAEs (maximum exposure to any study intervention was 27 months; follow-up for AEs=maximum up to 28 months; follow-up for SAEs=maximum up to 30 months)

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. Hematology parameters evaluated: hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Safety analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab.

Primary

From start of study treatment up to 30 days after last dose (maximum exposure to any study intervention was 27 months; follow-up = maximum up to 28 months)

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 severity 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. Safety analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab.

Primary

From start of study treatment up to 30 days after last dose for AEs (maximum exposure to any study intervention was 27 months)

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. 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. Safety analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab.

Primary

From start of study treatment up to 30 days after last dose (maximum exposure to any study intervention was 27 months; follow-up = maximum up to 28 months)

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). DLT-evaluable (DE) analysis = all treated participants in Part A who either(1) experienced a DLT or(2) received at least 75% of intended SGN-LIV1A and pembrolizumab doses and were followed for the full DLT evaluation period.

Primary

Cycle 1 (up to 21 days)

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. All treated analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab. Kaplan Meier method was used for 95% confidence interval.

Primary

From start of study treatment up to date of confirmed CR or PR (maximum up to 30 months)

DCR was defined as percentage of participants with CR, PR, or stable disease (SD) per 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. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression, taking as reference the smallest sum diameters while on study. Progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (this includes baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. Appearance of one or more new lesions. All treated analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab. Clopper-Pearson method was used for 95% confidence interval.

Secondary

From start of study treatment up to date of CR or PR or SD (maximum up to 30 months)

DOR = time from first documentation of objective response (subsequently confirmed) per investigator to first documentation of disease progression, or death due to any cause, whichever came first. CR: disappearance of all target lesions. Any pathological lymph nodes (reduction in short axis to <10 mm). PR: >=30% decrease in sum of diameters of target lesions, taking reference baseline sum diameters. Progression: at least a 20% increase in sum of diameters of target lesions, reference smallest sum on study (includes baseline sum if that is smallest on study). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 0.5 cm. Appearance of one or more new lesions. Kaplan-Meier method used for DOR evaluation. All treated analysis set evaluated. DOR was calculated for participants who achieved confirmed CR or PR. Here, “99999” and “-99999” suggests lower and upper limit of 95%CI could not be estimated due to insufficient participants with events.

Secondary

From the date of first CR or PR until the date of the first documentation of progression or death, or censoring date, whichever came first (maximum up to 30 months)

OS was defined as the time from start of study treatment to date of death due to any cause. In the absence of confirmation of death, OS was censored at the last date the participant was known to be alive. Kaplan-Meier method was used for OS evaluation. All treated analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab. Here, “99999” and “-99999” suggests that median and upper and/or lower limit of 95%CI could not be estimated due to insufficient participants with events.

Secondary

From start of study treatment until the date of death, or censoring date, whichever came first (maximum up to 30 months)

PFS was defined as the time from start of study treatment to first documentation of disease progression based upon the disease assessment per RECISTv1.1 or clinical progression, or to death due to any cause, whichever came first. Progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions. Kaplan-Meier method was used for PFS evaluation. All treated analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab. Here, ‘’99999’’ suggests that upper limit of 95%CI could not be estimated due to insufficient participants with events.

Secondary

From start of study treatment until the date of the first documentation of progression or death, or censoring date, whichever came first (maximum up to 30 months)

From start of study treatment up to 30 days and up to 90 days post last dose for AEs and SAEs respectively (maximum exposure to any study treatment = 27 months; follow-up: AEs = maximum up to 28 months; All-cause mortality, SAEs = maximum up to 30 months)

Same event may appear as both SAE and non-SAE but are distinct events. An event may be categorized as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE.

v27.1

Part C: SGN-LIV 1.0 mg/kg (Q1WK) + Pembrolizumab

Part C: SGN-LIV 1.25 mg/kg (Q1WK) + Pembrolizumab

Part D: SGN-LIV 1.5 mg/kg (2Q3WK) + Pembrolizumab

Part B: SGN-LIV 2.5 mg/kg (Q3WK) + Pembrolizumab

Part A: SGN-LIV 2.5 mg/kg (Q3WK) + Pembrolizumab

Part B: SGN-LIV 2.0 mg/kg (Q3WK) + Pembrolizumab

Part A: SGN-LIV 2.0 mg/kg (Q3WK) + Pembrolizumab