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
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT05852691
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 83
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Tobemstomig Participants will receive tobemstomig every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner. Arm A Nab-Paclitaxel Participants will receive tobemstomig every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner. Arm B Pembrolizumab Participants will receive pembrolizumab every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner. Arm B Nab-Paclitaxel Participants will receive pembrolizumab every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Objective Response Rate (ORR) Two consecutive occasions at least 4 weeks apart (up to approximately 24 months) 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) Overall Survival (OS) From randomization to death from any cause (up to approximately 24 months)
Trial Locations
- Locations (38)
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Cancer Blood and Specialty Clinic
🇺🇸Los Alamitos, California, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Novant Health Presbyterain Medical Center
🇺🇸Charlotte, North Carolina, United States
Novant Health Forsyth Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Fundación CENIT para la Investigación en Neurociencias
🇦🇷Buenos Aires, Argentina
Sunshine Hospital
🇦🇺St Albans, Victoria, Australia
Hospital Araujo Jorge
🇧🇷Goiania, Goiás, Brazil
Hospital do Cancer de Pernambuco - HCP
🇧🇷Recife, Pernambuco, Brazil
Hospital de Cancer de Barretos
🇧🇷Barretos, São Paulo, Brazil
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
🇧🇷Sao Paulo, São Paulo, Brazil
Fakultni Thomayerova nemocnice
🇨🇿Praha 4 - Krc, Czechia
Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH
🇩🇪Essen, Germany
Dres. Andreas Köhler und Roswitha Fuchs
🇩🇪Langen, Germany
Universitätsklinikum Ulm Am Michelsberg
🇩🇪Ulm, Germany
Komarom-Eszergom Varmegyei Szent Borbala Korhaz
🇭🇺Tatabánya, Hungary
Hadassah University Hospital - Ein Kerem
🇮🇱Jerusaelm, Israel
Ospedale Provinciale Santa Maria Delle Croci
🇮🇹Ravenna, Emilia-Romagna, Italy
Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Seoul National University Hospital
🇰🇷Seoul, 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
Health Pharma Professional Research
🇲🇽Cdmx, Mexico CITY (federal District), Mexico
OncoMed
🇲🇽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, Mexico
Centro Medico Monte Carmelo
🇵🇪Arequipa, Peru
Oncosalud Sac
🇵🇪Lima, Peru
Instituto Nacional de Enfermedades Neoplasicas
🇵🇪Lima, Peru
Instituto Peruano de Oncología y Radioterapia
🇵🇪Lima, Peru
?wi?tokrzyskie Centrum Onkologii
🇵🇱Kielce, Poland
Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
🇵🇱Kraków, Poland
Medical Oncology Centre of Rosebank
🇿🇦Johannesburg, South Africa
Hospital Quiron de Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Universitario Virgen de La Arrixaca
🇪🇸El Palmar, Murcia, Spain
National Taiwan Uni Hospital
🇨🇳Taipei, Taiwan