Primary Objective: This study will evaluate the efficacy, safety, and pharmacokinetics of RO7247669 plus nab-paclitaxel compared with pembrolizumab plus nab-paclitaxel in patients with previously untreated, locally advanced, unresectable or…
ID
Source
Brief title
Condition
- Other condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Health condition
TNBC
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PFS, defined as the time from randomization to the first occurrence of disease
progression, as determined by the investigator according to RECIST v1.1, or
death from any cause (whichever occurs first).
Secondary outcome
• ORR, defined as the proportion of participants with a CR or a PR on two
consecutive occasions >= 4 weeks apart, as determined by the investigator
according to RECIST v1.1
• DOR, defined as the time from the first occurrence of a confirmed objective
response to the first occurrence of disease progression, as determined by the
investigator according to RECIST v1.1, or death from any cause, whichever
occurs first
• OS, defined as the time from randomization to death from any cause
• PFS rate at 12 months, defined as the proportion of participants who have not
experienced disease progression or death from any cause at 12 months after
randomization, as determined by the investigator, according to RECIST v1.1
• OS rate at 12 months, defined as the proportion of participants who have not
experienced death from any cause at 12 months after randomization
• Incidence and severity of adverse events, with severity determined according
to NCI CTCAE v5.0
• Change from baseline in targeted clinical laboratory test results
• Change from baseline in targeted vital signs
• PK profiles and parameters derived for RO7247669 including but not limited
to, when appropriate and when data allow, the parameters listed below:
- Maximum concentration
- Time of maximum concentration
- Clearance
- Volume of distribution at steady state
- Area under the concentration-time curve
- Half*life
• Incidence and titer of RO7247669 ADA during the study relative to the
prevalence of ADA at baseline and impact of ADAs on exposure, activity and
safety
Background summary
Breast cancer is the most frequently diagnosed cancer among women, and the
leading cause of cancer-related deaths in women worldwide.
TNBC is characterized immunohistologically by the lack of expression of
hormonal estrogen receptor (ER) and progesterone receptor (PgR), and lack of
overexpression and/or amplification of the human epidermal growth factor
receptor 2 (HER2)/neuraminidase (NEU) gene . Patients with metastatic TNBC have
relatively poorer outcomes (shorter duration of progression-free survival [PFS]
and overall survival [OS]) compared with patients with other breast cancer
subtypes.
The treatment approach for this disease in the first-line (1L) setting is
chemotherapy, in combination with an anti-programmed death-1 (PD-1)/PD-L1
inhibitor for patients with PD-L1*positive TNBC.
Despite the advances lately, OS in the 1L metastatic setting remains modest at
less than 3 years. Therefore, there remains an urgency to improve upon
chemotherapy in combination with PD*1/PD*L1*targeting agents in 1L PD-L1
positive advanced TNBC. Combinations targeting novel immune checkpoints are
attractive because they aim to take advantage of distinct mechanisms that could
improve the success of immunotherapy in TNBC and potentially expand the
proportion of patients whose tumors respond to immunotherapy
Study objective
Primary Objective: This study will evaluate the efficacy, safety, and
pharmacokinetics of RO7247669 plus nab-paclitaxel compared with pembrolizumab
plus nab-paclitaxel in patients with previously untreated, locally advanced,
unresectable or metastatic PD-L1-positive TNBC.
Secondary objective:
- To evaluate the efficacy of RO7247669 plus nab-paclitaxel compared with
pembrolizumab plus nab-paclitaxel in the FAS
- To evaluate the efficacy of RO7247669 plus nab-paclitaxel compared with
pembrolizumab plus nab-paclitaxel in SP263-positive analysis set and
22C3-positive analysis set and SP142-positive analysis set
- To evaluate the safety of RO7247669 plus nab-paclitaxel compared with
pembrolizumab plus nab-paclitaxel in the SAS
- To characterize the RO7247669 PK profile
- To evaluate the immunogenicity to RO7247669
The exploratory objectives are described in protocol section 3
Study design
This is a Phase II, randomized, double-blind, global, multicenter study
designed to evaluate the efficacy, safety, and pharmacokinetics of RO7247669 in
combination with nab-paclitaxel compared with pembrolizumab plus nab-paclitaxel
in patients with previously untreated, locally advanced, unresectable or
metastatic (Stage IV) PD*L1-positive TNBC.
Intervention
RO7247669 plus nab-paclitaxel compared with pembrolizumab plus nab-paclitaxel
Study burden and risks
The general burden for the patient consists of (a.o.) the withdrawal of blood
samples, possible collection of tumor sample,
administration of investigational products which may lead to various adverse
events. These are described in the Investigators'
Brochure of RO7247669 and Pembrolizumab and Nab-Paclitaxel.
Beneluxlaan 2A
Woerden 3446AA
NL
Beneluxlaan 2A
Woerden 3446AA
NL
Listed location countries
Age
Inclusion criteria
• 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)
• 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
• 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 (see
Appendix 9)
More inclusion criteria are stated in protocol section 5.1
Exclusion criteria
• 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.
• 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
• 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%)
• Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases
More exclusion criteria are stated in the protocol section 5.2
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2022-502457-34-00 |
| CCMO | NL84956.000.23 |