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.
Recurrent or persistent endometrial carcinoma which has progressed or recurred after at least 1, but no more than 2, prior lines of therapy. Prior hormonal therapies (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit. Chemotherapy given in conjunction with radiotherapy as a radiosensitizer will be counted as a systemic therapeutic regimen.
Measurable disease per RECIST 1.1
Availability of a representative tumor specimen that is suitable for determination of biomarker status via central testing (F1CDx) OR If a patient has a prior F1CDx report from 1 September 2019 or later, those NGS results can be used to determine biomarker status as long as the tumor tissue used in the report was obtained within 5 years prior to prescreening and appropriate signed consent is obtained from the patient.
Life expectancy > 12 weeks
Endometrial tumors with the following histologies: squamous carcinomas, sarcomas
Other invasive malignancies within the last 5 years, except for non-melanoma skin cancer with no evidence of disease within the past 5 years AND localized breast cancer with previous adjuvant chemotherapy treatment for breast cancer completed > 5 years ago
Synchronous primary invasive ovarian or cervical cancer
Have an active or history of autoimmune disease or immune deficiency
Parallel
Atezolizumab - 28 Day Cycle
DrugAtezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
Bevacizumab
DrugBevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.
Ipatasertib
DrugIpatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
Talazoparib
DrugTalazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.
Trastuzumab emtansine
DrugTrastuzumab 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
DrugTiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.
Atezolizumab - 21 Day Cycle
DrugAtezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.
Inavolisib
DrugInavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.
Letrozole
DrugLetrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.
Giredestrant
DrugGiredestrant will be given orally at a dosage of 30 mg once daily for each day of the 28-day cycle.
Abemaciclib
DrugGiredestrant will be given orally at a dosage of 150 mg twice daily for each day of the 28-day cycle.
7
Treatment groupsSee each treatment group below.
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.
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
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
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.
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.
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.
Safety of each biomarker cohort: adverse events
AFT-50A Protocol: The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), as well as summaries of changes in clinically relevant laboratory test results, changes in vital signs, and study treatment exposures for each biomarker cohort
The safety of each biomarker cohort: Adverse Events
AFT-50B Protocol: The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). Summaries of changes in clinically relevant laboratory test results, changes in vital signs, and study treatment exposures for each biomarker cohort
Assess exploratory biomarkers in tumor tissue and peripheral blood, and their association with other molecular characteristics, disease status and/or participant response to study treatment
AFT-50A and AFT-50B Protocols: Association of exploratory biomarkers with clinical outcomes, including but not limited to molecular analysis of tumor tissue and peripheral blood, as well as cytokine/chemokine and cellular analysis of peripheral blood.
Click on the lead sponsor to view all of their trials.
Alliance Foundation Trials, LLC.
Lead sponsor
Genentech, Inc.
Collaborator
Foundation Medicine
Collaborator
Pfizer
Collaborator
Eli Lilly and Company
Collaborator
