A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
This is an umbrella study evaluating the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer.
The study will be performed in two stages. During Stage 1, four cohorts will be enrolled in parallel in this study:
Cohort 1 will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line \[1L\] PD-L1+ cohort).
Cohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line \[2L\] CIT-naive cohort).
Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative disease with PIK3CA mutation who may or may not have had disease progression during or following previous lines of treatment for metastatic disease (HR+cohort).
Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+ /HER2-low cohort).
In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). In addition, participants in the 2L CIT-nave cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination (Stage 2), provided Stage 2 is open for enrollment.
The study will be performed in two stages. During Stage 1, four cohorts will be enrolled in parallel in this study:
Cohort 1 will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line \[1L\] PD-L1+ cohort).
Cohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line \[2L\] CIT-naive cohort).
Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative disease with PIK3CA mutation who may or may not have had disease progression during or following previous lines of treatment for metastatic disease (HR+cohort).
Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+ /HER2-low cohort).
In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). In addition, participants in the 2L CIT-nave cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination (Stage 2), provided Stage 2 is open for enrollment.
Breast,
Phase I
Phase I/II
Adults
Chemotherapy - cytotoxic,
Hormonal Therapy,
Mol. targeted/Immunotherapy/Biologics
Abemaciclib,
Atezolizumab,
Capecitabine,
Carboplatin,
Eribulin,
Fulvestrant,
Gemcitabine,
Inavolisib,
Ipatasertib,
Letrozole (Femara),
Nab-Paclitaxel,
Ribociclib,
SGN-LIV1A,
Sacituzumab govitecan,
Tocilizumab,
Trastuzumab Deruxtecan (T-DXd)
Kennedy, Laura
International
Vanderbilt University
09-01-2021
Eligibility
18 Years and older
ALL
false
Inclusion Criteria:
Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-nave cohort):
Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-nave cohort):
Age >/= 18 years at the time of signing Informed Consent Form
Age >/= 18 years at the time of signing Informed Consent Form
ECOG Performance Status of 0 or 1
ECOG Performance Status of 0 or 1
Able to comply with the study protocol, in the investigator's judgment
Able to comply with the study protocol, in the investigator's judgment
Metastatic or inoperable locally advanced breast cancer
Metastatic or inoperable locally advanced breast cancer
Measurable disease (at least one target lesion) according to RECIST v1.1
Measurable disease (at least one target lesion) according to RECIST v1.1
Life expectancy >/= 3 months, as determined by the investigator
Life expectancy >/= 3 months, as determined by the investigator
Tumor accessible for biopsy, unless archival tissue is available
Tumor accessible for biopsy, unless archival tissue is available
Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing
Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing
Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment
Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
Exclusion Criteria:
Exclusion Criteria for Stage 1
Exclusion Criteria for Stage 1
Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds
Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
Adverse events from prior anti-cancer therapy that have not resolved to Grade
Adverse events from prior anti-cancer therapy that have not resolved to Grade
Eligibility only for the control arm
Eligibility only for the control arm
Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-nave cohort)
Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-nave cohort)
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Uncontrolled tumor-related pain
Uncontrolled tumor-related pain
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
History of leptomeningeal disease
History of leptomeningeal disease
Active or history of autoimmune disease or immune deficiency
Active or history of autoimmune disease or immune deficiency
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.
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
Active tuberculosis
Severe infection within 4 weeks prior to initiation of study treatment
Severe infection within 4 weeks prior to initiation of study treatment
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Significant cardiovascular disease
Significant cardiovascular disease
Prior allogeneic stem cell or solid organ transplantation
Prior allogeneic stem cell or solid organ transplantation
History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-nave cohort):
Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-nave cohort):
Age >/= 18 years at the time of signing Informed Consent Form
Age >/= 18 years at the time of signing Informed Consent Form
ECOG Performance Status of 0 or 1
ECOG Performance Status of 0 or 1
Able to comply with the study protocol, in the investigator's judgment
Able to comply with the study protocol, in the investigator's judgment
Metastatic or inoperable locally advanced breast cancer
Metastatic or inoperable locally advanced breast cancer
Measurable disease (at least one target lesion) according to RECIST v1.1
Measurable disease (at least one target lesion) according to RECIST v1.1
Life expectancy >/= 3 months, as determined by the investigator
Life expectancy >/= 3 months, as determined by the investigator
Tumor accessible for biopsy, unless archival tissue is available
Tumor accessible for biopsy, unless archival tissue is available
Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing
Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing
Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment
Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
Exclusion Criteria:
Exclusion Criteria for Stage 1
Exclusion Criteria for Stage 1
Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds
Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
Adverse events from prior anti-cancer therapy that have not resolved to Grade
Adverse events from prior anti-cancer therapy that have not resolved to Grade
Eligibility only for the control arm
Eligibility only for the control arm
Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-nave cohort)
Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-nave cohort)
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Uncontrolled tumor-related pain
Uncontrolled tumor-related pain
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
History of leptomeningeal disease
History of leptomeningeal disease
Active or history of autoimmune disease or immune deficiency
Active or history of autoimmune disease or immune deficiency
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.
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
Active tuberculosis
Severe infection within 4 weeks prior to initiation of study treatment
Severe infection within 4 weeks prior to initiation of study treatment
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Significant cardiovascular disease
Significant cardiovascular disease
Prior allogeneic stem cell or solid organ transplantation
Prior allogeneic stem cell or solid organ transplantation
History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Pregnancy or breastfeeding, or intention of becoming pregnant during the study
