Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer

Triple Negative Breast Neoplasms Clinical Trial

Official title:

Single Arm, Open Label Phase 1b/2 Study of SGN-LIV1A in Combination With Pembrolizumab for First-Line Treatment of Patients With Unresectable Locally-Advanced or Metastatic Triple-Negative Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03310957
• Other study ID #: SGNLVA-002
• Secondary ID: KEYNOTE 7212017-
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 27, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial studies ladiratuzumab vedotin (LV) with pembrolizumab in patients with triple-negative breast cancer. It will find out what side effects happen when participants get these two drugs. A side effect is anything the drugs do besides treating cancer. Pembrolizumab is a drug that can be used to treat triple-negative breast cancer. The trial will also find out if these drugs work to treat this type of cancer. Participants in this study have metastatic breast cancer. This means the cancer has spread to other parts of the body.

Description:

The primary goal of this study is to evaluate the combination of LV, which targets LIV-1- expressing tumor cells, with the checkpoint inhibitor pembrolizumab for patients with unresectable locally-advanced or metastatic triple-negative breast cancer. These two drugs act through distinct and possibly complementary modes of action.

This is a single-arm, open-label, multicenter trial. Patients given LV and pembrolizumab during dose escalation will be monitored for frequency of dose-limiting toxicities to determine a recommended doses for expansion cohorts. In addition to safety measures, objective response rate, progression-free survival, overall survival, and other efficacy outcomes will be assessed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 186
• Est. completion date: December 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-advanced breast cancer or metastatic breast cancer

• At least 6 months since prior treatment with curative intent and recurrence

• At least 1 tumor 10mm in diameter or greater OR lymph node of at least 15 mm in short axis

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Able to provide biopsy tissue for biomarker analysis

• Meet baseline laboratory data criteria

Exclusion Criteria:

• Prior immune-oncology therapy

• Pre-existing neuropathy of at least Grade 2

• History of carcinomatous meningitis or active central nervous system (CNS) metastases. Patients are eligible if CNS metastases are adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. Patients must be off corticosteroids.

• Received prior radiotherapy within 2 weeks of start of study treatment or have not adequately recovered from prior radiotherapy

• Active autoimmune disease requiring systemic treatment within the past 2 years

• History of interstitial lung disease

• Current pneumonitis or history of pneumonitis requiring steroids

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• ladiratuzumab vedotin
Given into the vein (IV; intravenously)
• Pembrolizumab
IV infusion every 3 weeks

Locations

Country	Name	City	State
Germany	Gynakologisches Zentrum Bonn Friedensplatz	Bonn	Other
Germany	Marien Hospital Bottrop	Bottrop	Other
Germany	Stadtisches Klinikum Dessau	Dessau	Other
Germany	Universitatsklinikum Erlangen	Erlangen	Other
Germany	Kliniken Essen-Mitte - Evang. Huyssens-Stiftung	Essen	Other
Germany	Klinikum Rechts der Isar der Technischen Universitaet Muenchen	Muenchen	Other
Germany	Klinikum der Universitat Munchen	Munchen	Other
Germany	Rotkreuzklinikum Munich	Munich	Other
Korea, Republic of	Pusan National University Hospital	Busan	Other
Korea, Republic of	CHA Bundang Medical Center	Seongnam	Other
Korea, Republic of	Korea Cancer Center Hospital	Seoul	Other
Korea, Republic of	Samsung Medical Center	Seoul	Other
Korea, Republic of	Seoul National University Hospital	Seoul	Other
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Other
Spain	Hospital del Mar	Barcelona	Other
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Other
Spain	Complejo Hospitalario de Jaen	Jaen	Other
Spain	L'Institut Catala d'Oncologia	L'Hospitalet de Llobregat	Other
Spain	Complejo Hospitalario Universitario La Coruna	La Coruna	Other
Spain	HM Centro Integral Oncologico Clara Campal	Madrid	Other
Spain	Hospital Ruber Internacional	Madrid	Other
Spain	Hospital Universitario 12 de Octubre	Madrid	Other
Spain	MD Anderson Cancer Center - Madrid	Madrid	Other
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcon	Other
United States	New Mexico Cancer Center	Albuquerque	New Mexico
United States	Piedmont Cancer Institute	Atlanta	Georgia
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Virginia	Charlottesville	Virginia
United States	Texas Oncology - Baylor Sammons Cancer Center	Dallas	Texas
United States	Summit Medical Group	Florham Park	New Jersey
United States	Ingalls Cancer Care / Ingalls Memorial Hospital	Harvey	Illinois
United States	Texas Oncology - Houston Memorial City	Houston	Texas
United States	Saint Luke's Cancer Institute LLC	Kansas City	Missouri
United States	Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	Cardinal Bernardin Cancer Center / Loyola University Medical Center	Maywood	Illinois
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida
United States	Allina Health Cancer Institute	Minneapolis	Minnesota
United States	Weill Cornell Medicine	New York	New York
United States	Helen F. Graham Cancer Center / Christiana Care Health Systems	Newark	Delaware
United States	The Whittingham Cancer Center / Norwalk Hospital	Norwalk	Connecticut
United States	Chao Family Comprehensive Cancer Center University of California Irvine	Orange	California
United States	University of California Irvine - Newport	Orange	California
United States	AdventHealth Cancer Institute	Orlando	Florida
United States	University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Texas Oncology - San Antonio Medical Center Northeast	San Antonio	Texas
United States	Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Germany,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed objective response rate	Confirmed ORR as determined by investigator according to RECIST v 1.1	Up to 18 weeks following last dose; approximately 1 year
Primary	Incidence of adverse events		Through 1 month following last dose; approximately 10 months
Primary	Incidence of laboratory abnormalities		Through 1 month following last dose; approximately 10 months
Primary	Incidence of dose-limiting toxicities		Through 1 month following last dose; approximately 10 months
Secondary	Duration of response	DOR as determined by investigator according to RECIST v 1.1	Up to 2.5 years following last dose
Secondary	Disease control rate	Proportion of patients with complete response (CR), partial response (PR), or stable disease (SD) as determined by investigator according to RECIST v 1.1	Up to 2.5 years following last dose
Secondary	Progression-free survival	PFS as determined by investigator according to RECIST v 1.1	Up to 2.5 years following last dose
Secondary	Overall survival	OS is defined as the time from start of study treatment to date of death due to any cause.	Up to 2.5 years following last dose