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

• ClinicalTrials.gov Identifier: NCT05852691
• Recruitment Status: Recruiting
• First Posted: May 10, 2023
• Last Update Posted: May 21, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: May 2, 2023
• First Posted Date: May 10, 2023
• Last Update Posted Date: May 21, 2024
• Actual Study Start Date: July 18, 2023
• Estimated Primary Completion Date: December 1, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 7, 2023): Progression-Free Survival (PFS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 24 months) ]
• Original Primary Outcome Measures (submitted: May 2, 2023): Progression-Free Survival (PFS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 30 months) ]

Current Secondary Outcome Measures (submitted: December 7, 2023)

• Objective Response Rate (ORR) [ Time Frame: Two consecutive occasions at least 4 weeks apart (up to approximately 24 months) ]
• Duration of Response (DOR) [ Time Frame: 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) [ Time Frame: From randomization to death from any cause (up to approximately 24 months) ]
• PFS rate at 12 months [ Time Frame: 12 months after randomization ]
• OS rate at 12 months [ Time Frame: 12 months after randomization ]
• Serum Concentration of Tobemstomig [ Time Frame: Up to approximately 24 months ]
• Incidence of Anti-Drug Antibodies (ADAs) to Tobemstomig [ Time Frame: Up to approximately 24 months ]

Original Secondary Outcome Measures (submitted: May 2, 2023)

• Objective Response Rate (ORR) [ Time Frame: Two consecutive occasions at least 4 weeks apart (up to approximately 30 months) ]
• Duration of Response (DOR) [ Time Frame: 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 30 months) ]
• Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to approximately 30 months) ]
• PFS rate at 12 months [ Time Frame: 12 months after randomization ]
• OS rate at 12 months [ Time Frame: 12 months after randomization ]
• Serum Concentration of RO7247669 [ Time Frame: Up to approximately 30 months ]
• Incidence of Anti-Drug Antibodies (ADAs) to RO7249669 [ Time Frame: Up to approximately 30 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Breast Cancer

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.
  Other Name: RO7247669
• Drug: Pembrolizumab
  Participants will receive IV pembrolizumab Q3W 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.

Study Arms

• 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.
  Interventions:

  • Drug: Tobemstomig
  • Drug: Nab-Paclitaxel
• 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.
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Nab-Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 2, 2023): 160
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 27, 2026
• Estimated Primary Completion Date: December 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Argentina, Australia, Brazil, Czechia, Denmark, Germany, Hungary, Israel, Italy, Korea, Republic of, Mexico, Peru, Poland, South Africa, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT05852691
• Other Study ID Numbers: CO44194
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2024