RO7247669 Combined With Nab-Paclitaxel in Triple-Negative Breast Cancer

What is the Purpose of this Study?

This study focuses on individuals who have a type of breast cancer called triple-negative breast cancer (and who are not surgical candidates) or whose cancer is metastatic (spread to other parts of the body) and have not received prior therapy for metastatic disease. The study will evaluate an experimental drug called RO7247669 used in combination with nab-paclitaxel (a common type of chemotherapy used to treat breast cancer). Researchers will compare the effects of RO7247669 versus another drug, pembrolizumab (in combination with nab-paclitaxel). Participants will receive either RO7247669 in combination with nab paclitaxel or pembrolizumab in combination with nab-paclitaxel. By blocking specific proteins in cells, RO7247669 may help the immune system stop or reverse the growth of tumors. Pembrolizumab is approved by the U.S. Food and Drug Administration (FDA) for various types of cancer, but its use in this study is considered investigational.

Eligibility

* 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

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

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Where can I participate?

Cedars-Sinai Cancer at Beverly Hills (THO) : Nikki Kem-Bernard
Cedars-Sinai Cancer at Hunt Cancer Center - TMPNCC (CSMC Affiliate)
Cedars-Sinai Cancer at SOCC : Nikki Kem-Bernard

More about this Clinical Trial

What is the full name of this clinical trial?

CO44194: A Phase II, Multicenter, Randomized, Double-Blind Study of 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

Study Details

Disease Type/Condition

Breast

Principal Investigator

Yuan, Yuan

Co-Investigators

Andrew Horodner, David Chan, Dorothy Park, Hugo Hool, Jin Sun Bitar, Maryliza El-Masry, Philomena McAndrew, Swati Sikaria, Syed Jilani, Thomas Lowe, Vanessa Dickey

Age Group

Adult

Phase

IRB Number

STUDY00002826

ClinicalTrials.gov ID

NCT05852691

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Nikki Kem-Bernard

Nikki.Bernard@cshs.org