This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents with or without cancer immune checkpoint therapy with atezolizumab in participant with recurrent and/or persistent endometrial cancer. The main protocol provides a platform for genomic screening with homogeneous basic eligibility criteria in order to direct study participants into biomarker-matched study cohorts consisting of testing targeted agents.
This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents with or without cancer immune checkpoint therapy with atezolizumab in participants with recurrent and/or persistent endometrial cancer. This biomarker-driven study provides a platform whereby participants with persistent/recurrent endometrial cancer will be placed into study cohorts evaluating targeted agents selected on the basis of the tumor's specific genomic profile. Prospective participants with persistent and/or recurrent endometrial cancer will be prescreened within 60 days of treatment assignment to have a tumor tissue sample submitted for next-generation sequencing (NGS) using FoundationOne® companion diagnostic (CDx) testing prior to entering screening. If a participant has FoundationOne® CDx testing within five years of enrollment, the previous tumor tissue may be re-analyzed for use in the study. Non-FMI NGS testing may be submitted if approved. Depending on the cohort assignment per the tumor's biomarker profile, participants will be assigned to the AFT-50A Protocol (atezolizumab+targeted agent) or the AFT-50B Protocol (non-atezolizumab targeted agents). The current study cohorts are as follows: AFT-50A Cohorts * Atezolizumab + Bevacizumab doublet - Closed to Accrual * Atezolizumab + Ipatasertib doublet - Closed to Accrual * Atezolizumab + Talazoparib doublet * Atezolizumab + Trastuzumab emtansine (TDM-1) doublet - Closed to Accrual * Atezolizumab + Tiragolumab doublet - Closed to Accrual AFT-50B Cohorts * Inavolisib + Letrozole doublet * Giredestrant + Abemaciclib doublet It is anticipated that approximately 20 participants will be enrolled in each study cohort in AFT-50A and 24 participants in each study cohort in AFT-50B, unless otherwise specified for a given cohort due to statistical considerations. Each study cohort will open/close independently of other study cohorts. Once a study cohort reaches the prespecified number of participants, it will be closed to further enrollment, unless an expansion phase is planned. The study is structured to allow for additional cohorts to be added as the study progresses. These additional study cohorts may be proposed by investigators, but requires approval by the Steering Committee in order to be added to the protocol.
Study Type
Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
Bevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.
Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
Investigator-assessed overall response rate (ORR) of each biomarker cohort
AFT-50A Protocol: Overall response rate for each biomarker cohort is defined as the proportion of participants achieving a complete (CR) or partial (PR) response on two consecutive occasions at least 4 weeks apart, as determined by the investigator from AFT50A Protocol: Tumor assessments per RECIST v1.1.
Time frame: 48 Months
The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 6 months
AFT-50B Protocol: Progression free survival rate at 6 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1
Time frame: 6 Months
Relative proportion of participants in each biomarker cohort who remain progression-free for at least 6 months compared to that from historical control studies
AFT-50A Protocol: PFS rate at 6 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1
Time frame: 6 Months per cohort
Investigator assessed disease-control rate of each biomarker cohort
AFT-50A Protocol: Disease-control rate is defined as the proportion of participants achieving either stable disease, complete response, or partial response.
Time frame: 48 Months
Duration of response for participants in each biomarker cohort who achieve a complete or partial response.
AFT-50A Protocol: Duration of response is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
Quality Management and Compliance
CONTACT
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INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
148
Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.
Trastuzumab emtansine be given to participants intravenously at a dosage of 3.6 mg per participant kilogram, on day 1 of each 21-day cycle.
Tiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.
Atezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.
Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.
Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.
Giredestrant will be given orally at a dosage of 30 mg once daily for each day of the 28-day cycle.
Giredestrant will be given orally at a dosage of 150 mg twice daily for each day of the 28-day cycle.
City of Hope Comprehensive Cancer Center
Duarte, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
ACTIVE_NOT_RECRUITINGMedstar Georgetown Cancer Institute
Washington D.C., District of Columbia, United States
ACTIVE_NOT_RECRUITINGMount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States
ACTIVE_NOT_RECRUITINGUniversity of Chicago
Chicago, Illinois, United States
ACTIVE_NOT_RECRUITINGUniversity of Kansas Cancer Center
Westwood, Kansas, United States
ACTIVE_NOT_RECRUITINGMaine Medical Center
Scarborough, Maine, United States
ACTIVE_NOT_RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
ACTIVE_NOT_RECRUITINGUniversity of Minnesota
Minneapolis, Minnesota, United States
ACTIVE_NOT_RECRUITINGWashington University School of Medicine Siteman Cancer Center
St Louis, Missouri, United States
WITHDRAWN...and 11 more locations
Time frame: 48 Months
Overall survival (OS) rates of participants in each biomarker cohort after 24 months
AFT-50A Protocol: 24-month overall survival rate is defined as the proportion of participants who have not experienced death from any cause at 24 months.
Time frame: 24 Months per cohort
Investigator assessed disease-control rate of each biomarker cohort
AFT-50B Protocol: Disease control rate is defined as the proportion of participants achieving either stable disease, complete response, or partial response at any time.
Time frame: 48 Months
Duration of response for participants in each biomarker cohort who achieve a confirmed response (complete or partial)
AFT-50B Protocol: Duration of response is defined as the time from the first occurrence of a documented objective response (complete or partial) to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Time frame: 48 Months
Overall survival rates of participants in each biomarker cohort
AFT-50B Protocol: 24-month overall survival rate is defined as the proportion of participants who have not experienced death from any cause at 24 months.
Time frame: 24 Months