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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tobemstomig; Drug: Nab-Paclitaxel; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: CO44194 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABD
    • Recruiting
    • Fundacion CENIT para la Investigacion en Neurociencias
  • Buenos Aires, Argentina, C1431FWN
    • Recruiting
    • Cemic; Oncologia Clinica
  • Caba, Argentina, C1426AGE
    • Recruiting
    • Centro Oncologico Korben
  • La Rioja, Argentina, F5300COE
    • Recruiting
    • Centro Oncologico Riojano Integral (CORI)
  • Rosario, Argentina, S2000DSV
    • Recruiting
    • Sanatorio Parque de Rosario
  • Rosario, Argentina, S2002KDS
    • Recruiting
    • Hospital Provincial del Centenario
• Australia
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Recruiting
      • ICON Cancer Care Adelaide
  • Victoria
    • St Albans, Victoria, Australia
      • Active, not recruiting
      • Sunshine Hospital; Oncology Research
  • Western Australia
    • Bull Creek, Western Australia, Australia, 6149
      • Recruiting
      • Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
• Brazil
  • GO
    • Goiania, GO, Brazil, 74605-070
      • Recruiting
      • Hospital Araujo Jorge; Departamento de Ginecologia E Mama
  • PE
    • Recife, PE, Brazil, 50040-000
      • Recruiting
      • Hospital do Cancer de Pernambuco - HCP
  • RO
    • Porto Velho, RO, Brazil, 76834-899
      • Recruiting
      • Hospital de Amor Amazônia
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Recruiting
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, RS, Brazil, 90040-373
      • Recruiting
      • Hospital Nossa Senhora da Conceição
  • SP
    • Barretos, SP, Brazil, 14784-400
      • Recruiting
      • Hospital de Cancer de Barretos
    • Sao Paulo, SP, Brazil, 01317-001
      • Recruiting
      • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
• Czechia
  • Novy Jicin, Czechia, 741 01
    • Recruiting
    • Nemocnice AGEL Novy Jicin a.s.; Oddeleni radioterapie a onkologie
  • Olomouc, Czechia, 779 00
    • Recruiting
    • Fakultni nemocnice Olomouc; Onkologicka klinika
  • Praha 4 - Krc, Czechia, 140 59
    • Recruiting
    • Fakultni Thomayerova nemocnice; Onkologicka klinika 1. LF UK a FTN
  • Praha 5, Czechia, 150 06
    • Recruiting
    • Fakultni nemocnice v Motole; Onkologicka klinika 2. LF UK a FN Motol
• Germany
  • Freiburg, Germany, 79110
    • Recruiting
    • Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
  • Hannover, Germany, 30625
    • Withdrawn
    • Medizinische Hochschule Zentrum Frauenheilkunde Abt.Gynäkologische Onkologie
  • Koblenz, Germany, 56068
    • Recruiting
    • InVO - Institut für Versorgungsforschung in der Onkologie GbR
  • Langen, Germany, 63225
    • Recruiting
    • Dres. Andreas Köhler und Roswitha Fuchs
• Israel
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah University Hospital - Ein Kerem; Oncology
  • Ramat Gan, Israel, 5262100
    • Recruiting
    • Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Sourasky / Ichilov Hospital; Dept. of Oncology
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06273
    • Active, not recruiting
    • Gangnam Severance Hospital, Yonsei University Health System
• Mexico
  • Mexico CITY (federal District)
    • Cdmx, Mexico CITY (federal District), Mexico, 03100
      • Recruiting
      • Health Pharma Professional Research
    • Ciudad de México, Mexico CITY (federal District), Mexico, 03100
      • Active, not recruiting
      • OncoMed; Supportive Care
  • Oaxaca
    • Oaxaca de Juárez, Oaxaca, Mexico, 68020
      • Recruiting
      • Centro de Investigacion Clinica de Oaxaca
• Peru
  • Lima, Peru, Lima 34
    • Recruiting
    • Instituto Nacional de Enfermedades Neoplasicas
• Poland
  • Bydgoszcz, Poland, 85-796
    • Recruiting
    • Centrum Onkologii im. Prof. Franciszka ?ukaszczyka; Ambulatorium Chemioterapii
  • Kielce, Poland, 25-734
    • Recruiting
    • ?wi?tokrzyskie Centrum Onkologii; Dzia? Chemioterapii
• South Africa
  • Johannesburg, South Africa, 2196
    • Recruiting
    • Medical Oncology Centre of Rosebank; Oncology
  • Port Elizabeth, South Africa, 6045
    • Recruiting
    • Cancercare
• Spain
  • Malaga, Spain, 29010
    • Recruiting
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
  • LA Coruña
    • Santiago de Compostela, LA Coruña, Spain, 15706
      • Recruiting
      • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Universitario Virgen de La Arrixaca; Servicio De Oncologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Complejo Hospitalario de Navarra; Servicio de Oncologia
• Taiwan
  • Taipei, Taiwan, 00112
    • Recruiting
    • VETERANS GENERAL HOSPITAL; Department of General Surgery
  • Taipei, Taiwan, 100
    • Active, not recruiting
    • National Taiwan Uni Hospital; Dept of Oncology
  • Taipei City, Taiwan, 11259
    • Recruiting
    • Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
  • Taoyuan City, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hosipital at Linkou
• United States
  • California
    • Los Alamitos, California, United States, 90720
      • Recruiting
      • Cancer Blood and Specialty Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Recruiting
      • Mercy Medical Center
    • Frederick, Maryland, United States, 21701
      • Recruiting
      • Frederick Health Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health Presbyterain Medical Center
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Novant Health Forsyth Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Recruiting
      • Providence Oncology and Hematology Care Clinic - Westside
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Cancer Inst.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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.	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.; Other Names: RO7247669; Drug: 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.
Active Comparator: Arm B; 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.	Drug: 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.; Drug: Pembrolizumab; Participants will receive IV pembrolizumab Q3W until disease progression or until up to 24 months after the first treatment, whichever is sooner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
PFS rate at 12 months	12 months after randomization
OS rate at 12 months	12 months after randomization
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)
Serum Concentration of Tobemstomig	Up to approximately 24 months
Incidence of Anti-Drug Antibodies (ADAs) to Tobemstomig	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): February 27, 2026

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Paclitaxel; Pembrolizumab
• Other Study ID Numbers: CO44194

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No