A Study of Tobemstomig + Nab-Paclitaxel Compared With Pembrolizumab + Nab-Paclitaxel in Participants With Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase II, Multicenter, Randomized, Double-Blind Study of Tobemstomig/RO7247669 Combined With Nab-Paclitaxel Compared With Pembrolizumab Combined With Nab-Paclitaxel in Participants With Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05852691
• Other study ID #: CO44194
• Status: Recruiting
• Phase: Phase 2
• Start date: July 18, 2023
• Est. completion date: February 27, 2026

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: CO44194 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of a novel immunotherapy candidate, tobemstomig, in combination with nab-paclitaxel, for patients with previously untreated, locally advanced, unresectable or metastatic (Stage IV) programmed death-ligand 1 (PD-L1)-positive triple-negative breast cancer (TNBC).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: February 27, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Metastatic or locally advanced unresectable, histologically documented triple-negative breast cancer (TNBC) (absence of HER2-over-expression, ER, and PgR expression by local assessment)

• HER2-low-status

• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

• If metastatic disease (Stage IV), measurable disease outside of the bone

• No prior systemic therapy for metastatic or locally advanced unresectable TNBC

• Tumor PD-L1 expression as documented through central testing of a representative tumor tissue specimen

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Adequate hematologic and end-organ function

• Negative HIV test at screening, with the following exception: individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count = 200/uL, and have an undetectable viral load

• Negative hepatitis B surface antigen (HBsAg) test at screening

• Positive hepatitis B surface antibody (HBsAb) test at screening, or a negative HBsAb at screening accompanied by either of the following: negative hepatitis B core antibody (HBcAb); positive HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL

• Negative hepatitis C virus (HCV) antibody test at screening, or a positive HCV antibody test followed by a negative HCV RNA test at screening

• Adequate cardiovascular function

Exclusion Criteria:

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 4 months after the final dose of tobemstomig or pembrolizumab, and 6 months after the final dose of nab-paclitaxel

• Poor venous access

• History of malignancy within 5 years prior to consent, except for the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer

• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases

• History of leptomeningeal disease

• Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)

• Hypercalcemia or hypercalcemia that is symptomatic

• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis (granulomatosis with polyangiitis), Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis

• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted

• Active tuberculosis (TB)

• Significant cardiovascular/cerebrovascular disease within 3 months prior to consent

• History or presence of an abnormal ECG that is deemed clinically significant

• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome

• Major surgical procedure within 4 weeks prior to initiation of study treatment

• Treatment with therapeutic oral or IV antimicrobials (anti-bacterial, anti-fungal, antiviral, anti-parasitic) within 1 week prior to initiation of study treatment

• Prior allogeneic stem cell or solid organ transplantation

• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications

• Treatment with a live, attenuated vaccine within 28 days prior to initiation of study treatment

• Treatment with investigational therapy within 28 days prior to initiation of study treatment

• Prior treatment with CD137 agonists or anti-CTLA therapeutic antibodies or an anti-LAG3 agent

• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment

• Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including, but not limited to, prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents) within 2 weeks prior to initiation of study treatment

• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the tobemstomig or pembrolizumab formulation

• Known allergy or hypersensitivity to any component of the to nab-paclitaxel formulation

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Tobemstomig
Participants will receive intravenous (IV) tobemstomig every 3 weeks (Q3W) until disease progression or until up to 24 months after the first treatment, whichever is sooner.
• Pembrolizumab
Participants will receive IV pembrolizumab Q3W until disease progression or until up to 24 months after the first treatment, whichever is sooner.
• Nab-Paclitaxel
Participants will receive IV nab-paclitaxel weekly for 3 weeks, followed by 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner.

Locations

Country	Name	City	State
Argentina	Cemic; Oncologia Clinica	Buenos Aires
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Centro Oncologico Korben	Caba
Argentina	Centro Oncologico Riojano Integral (CORI)	La Rioja
Argentina	Hospital Provincial del Centenario	Rosario
Argentina	Sanatorio Parque de Rosario	Rosario
Australia	Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit	Bull Creek	Western Australia
Australia	ICON Cancer Care Adelaide	Kurralta Park	South Australia
Australia	Sunshine Hospital; Oncology Research	St Albans	Victoria
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Hospital de Amor Amazônia	Porto Velho	RO
Brazil	Hospital do Cancer de Pernambuco - HCP	Recife	PE
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda	Sao Paulo	SP
Czechia	Nemocnice AGEL Novy Jicin a.s.; Oddeleni radioterapie a onkologie	Novy Jicin
Czechia	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc
Czechia	Fakultni Thomayerova nemocnice; Onkologicka klinika 1. LF UK a FTN	Praha 4 - Krc
Czechia	Fakultni nemocnice v Motole; Onkologicka klinika 2. LF UK a FN Motol	Praha 5
Denmark	Aalborg Universitetshospital; Onkologisk Afdeling	Aalborg
Denmark	Rigshospitalet; Onkologisk Klinik	København Ø
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
Denmark	Vejle Sygehus; Onkologisk Afdeling	Vejle
Germany	St. Johannes Hospital; Abt. für Hämatologie und Onkologie	Dortmund
Germany	Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum	Essen
Germany	Klinikum Esslingen; Klinik für Frauenheilkunde und Geburtshilfe	Esslingen
Germany	Praxis für Interdisziplinäre Onkologie und Hämatologie GbR	Freiburg
Germany	Medizinische Hochschule Zentrum Frauenheilkunde Abt.Gynäkologische Onkologie	Hannover
Germany	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg
Germany	InVO - Institut für Versorgungsforschung in der Onkologie GbR	Koblenz
Germany	Dres. Andreas Köhler und Roswitha Fuchs	Langen
Germany	Onkologische Schwerpunktpraxis Lübeck	Lübeck
Germany	Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde	Mainz
Germany	Gemeinschaftspraxis für Hämatologie und Onkologie	Münster
Germany	HELIOS Klinikum Schwerin; Frauenklinik	Schwerin
Germany	Universitätsklinikum Ulm Am Michelsberg; Frauenklinik	Ulm
Hungary	Somogy Varmegyei Kaposi Mor Oktato Korhaz; Onkologiai Osztaly	Kaposvár
Hungary	Bács-Kiskun Vármegyei Oktatókórház; Onkoradiológiai Központ	Kecskemét
Hungary	B-A-Z Vármegyei Központi Kórház és Egyetemi Oktatókórház; Klin. Onkológiai és Sugárterápiás Centrum	Miskolc
Israel	Hadassah University Hospital - Ein Kerem; Oncology	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Israel	Sourasky / Ichilov Hospital; Dept. of Oncology	Tel Aviv
Italy	RCCS - Centro di Riferimento; Oncologia Medica B	Aviano (PN)	Friuli-Venezia Giulia
Italy	Policlinico S.Orsola-Malpighi; Istituto Oncologia R. Addarii	Bologna	Emilia-Romagna
Italy	Ospedale S. Giuseppe; Oncologia	Empoli (FI)	Toscana
Italy	Ospedale Civile; Unita Operativa Di Oncologia Medica	Livorno	Toscana
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica	Milano	Lombardia
Italy	Ospedale San Raffaele; Medical Oncology	Milano	Lombardia
Italy	Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica	Ravenna	Emilia-Romagna
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	OncoMed; Supportive Care	Ciudad de México	Mexico CITY (federal District)
Mexico	Centro Médico Zambrano Hellion	Monterrey	Nuevo LEON
Mexico	Centro de Investigacion Clinica de Oaxaca	Oaxaca de Juárez	Oaxaca
Netherlands	Ziekenhuis Gelderse Vallei	EDE
Peru	Centro Medico Monte Carmelo	Arequipa
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Peru	Instituto Peruano de Oncología y Radioterapia	Lima
Peru	Oncosalud Sac; Oncología	Lima
Poland	Centrum Onkologii im. Prof. Franciszka ?ukaszczyka; Ambulatorium Chemioterapii	Bydgoszcz
Poland	Narodowy Instytut Onkologii Odzia? w Gliwicach; Centrum Diagnostyki i Leczenia Chorób Piersi	Gliwice
Poland	?wi?tokrzyskie Centrum Onkologii; Dzia? Chemioterapii	Kielce
Poland	Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii	Koszalin
Poland	Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii	Kraków
Poland	Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr	Warszawa
South Africa	Medical Oncology Centre of Rosebank; Oncology	Johannesburg
South Africa	Cancercare	Port Elizabeth
Spain	Hospital Universitario Virgen de La Arrixaca; Servicio De Oncologia	El Palmar	Murcia
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Complejo Hospitalario de Navarra; Servicio de Oncologia	Pamplona	Navarra
Spain	Hospital Quiron de Madrid; Servicio de Oncologia	Pozuelo de Alarcon	Madrid
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Taiwan	National Taiwan Uni Hospital; Dept of Oncology	Taipei
Taiwan	VETERANS GENERAL HOSPITAL; Department of General Surgery	Taipei
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology	Taipei City
Taiwan	Chang Gung Memorial Hosipital at Linkou	Taoyuan City
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Mercy Medical Center	Baltimore	Maryland
United States	Novant Health Presbyterain Medical Center	Charlotte	North Carolina
United States	Frederick Health Hospital	Frederick	Maryland
United States	University of Colorado Health Lone Tree Medical Center	Lone Tree	Colorado
United States	Cancer Blood and Specialty Clinic	Los Alamitos	California
United States	Lawrence J. Ellison Institute for Transformative Medicine	Los Angeles	California
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Providence Oncology and Hematology Care Clinic - Westside	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri
United States	UCSF Comprehensive Cancer Ctr	San Francisco	California
United States	Providence St Johns Health Center	Santa Monica	California
United States	Swedish Cancer Inst.	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Cedars Sinai Outpatient Cancer Center	West Hollywood	California
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Czechia,  Denmark,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Poland,  South Africa,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)		From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 24 months)
Secondary	Objective Response Rate (ORR)		Two consecutive occasions at least 4 weeks apart (up to approximately 24 months)
Secondary	Duration of Response (DOR)		From the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 24 months)
Secondary	Overall Survival (OS)		From randomization to death from any cause (up to approximately 24 months)
Secondary	PFS rate at 12 months		12 months after randomization
Secondary	OS rate at 12 months		12 months after randomization
Secondary	Serum Concentration of Tobemstomig		Up to approximately 24 months
Secondary	Incidence of Anti-Drug Antibodies (ADAs) to Tobemstomig		Up to approximately 24 months