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
- Conditions
- C50 Cancer de mama
- Registration Number
- PER-019-23
- Lead Sponsor
- F. HOFFMANN-LA ROCHE LTD.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- In enrollment
- Sex
- All
- Target Recruitment
- 12
Potential participants are eligible to be included in the study only if all of the following criteria apply:
? Signed Informed Consent Form
? Age = 18 years at the time of signing Informed Consent Form
? Metastatic or locally advanced unresectable, histologically documented TNBC (absence of HER2-over-expression, ER, and PgR expression by local assessment)
o HER2 negativity (it is recommended that labs follow American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP)
HER2 testing guidelines, and interpret as follows) by local laboratory assessment:
? In situ hybridization non-amplified (ratio of HER2 to CEP17 = 2.0 or single probe average HER2 gene copy number < 4 signals/cell), or
? IHC 0
o HER2-low-status (it is recommended that labs follow ASCO-CAP HER2 testing guidelines, and interpret as follows) by local laboratory assessment:
? IHC 2 + and in situ hybridization non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell), or
? IHC 1 + (and not required, but if performed, in situ hybridization non-amplified [ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell])
o ER and PgR negativity are defined as < 1% of cells expressing hormonal receptors via IHC analysis, with testing to be performed locally
? Measurable disease per RECIST v1.1
? If metastatic disease (Stage IV), measurable disease outside of the bone
? Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that same lesion since radiation
? No prior systemic therapy for metastatic or locally advanced unresectable TNBC
o Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy. Participants should have recovered from the effects of radiation.
o Prior systemic therapy for early breast cancer (resectable and non-metastatic, in the neoadjuvant and/or adjuvant setting) is permitted. If prior systemic therapy was given for early TNBC, it must have included anthracycline and taxane.
o Prior systemic therapy for early breast cancer is permitted if treatment was completed = 12 months prior to initiation of study treatment (Cycle 1, Day 1).
o Prior anti-PD-1 or anti-PD-L1 therapeutic antibody exposure (e.g., atezolizumab or pembrolizumab) in the neoadjuvant and/or adjuvant setting is allowable if treatment was completed = 12 months prior to initiation of study treatment (Cycle 1, Day 1).
? Tumor PD-L1 expression as documented through central testing of a representative tumor tissue specimen.
o An FFPE tumor specimen in a paraffin block (preferred) or at least 20 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report. Tumor tissue must be obtained from a biopsy performed within the 3 months prior to consent. If no tumor tissue collected within the 3 months prior to consent is available, fresh tissue may be obtained or archival tissue may be used. Bone is not an acceptable source of tumor tissue.
o Tumor tissue should be of good quality based on total and viable tumor content and will be evaluated prospectively at a central laboratory for PD-L1 expression and must be determined to be positive, as determined using:
? the investigational VENTANA PD-L1 (SP142) Assay (positive: at least 1% of t
Potential participants are excluded from the study if any of the following criteria apply:
? Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 4 months after the final dose of RO7247669 or pembrolizumab, and 6 months after the final dose of nab-paclitaxel.
Female participants of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
? Poor venous access
? Glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 as calculated through use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
GFR should be assessed by calculation through use of the CKD-EPI equation:
CKD-EPI = 142 x (serum creatinine/A)B x 0.9938Age x (1.012 if female), where A and B are the following:
? Female serum creatinine = 0.7 mg/dL: A = 0.7 and B = -0.241
? Female serum creatinine > 0.7 mg/dL: A = 0.7 and B = -1.2
? Male serum creatinine = 0.9 mg/dL: A = 0.9 and B = -0.302
? Male serum creatinine > 0.9 mg/dL: A = 0.9 and B = -1.2
To allow for appropriate nab-paclitaxel dosing, individualized body surface area (BSA) adjusted GFR values should be used (multiply the standardized GFR by the individual’s BSA, calculated using an appropriate formula, and divide by 1.73).
? 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
o Asymptomatic participants with treated CNS lesions are eligible if all of the following criteria are met:
- Measurable disease, per RECIST v1.1, must be present outside the CNS.
- The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
- The participant has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
- The participant has no ongoing requirement for corticosteroids as therapy for CNS disease.
- If the participant is receiving anti-convulsant therapy, the dose is considered stable (per the investigator’s judgment).
- Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
- No evidence of significant vasogenic edema.
- There is no evidence of interim progression (per the investigator’s judgment) between completion of CNS-directed therapy and initiation of study treatment.
- Asymptomatic participants with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy and/or surgery, with no need to repeat the screening brain scan.
? History of leptomeningeal disease
? Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Participants with indwelling catheters (e.g., PleurX®) are allowed.
? Hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL, or corrected calcium > ULN) or hypercalcemia t
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method As determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first).<br> NAME OF THE RESULT: Progression-free survival (PFS)<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: From randomization to the first occurrence of disease progression
- Secondary Outcome Measures
Name Time Method