Ignite Creation Date:
2024-05-06 @ 5:50 PM
Last Modification Date:
2024-10-26 @ 2:37 PM
Study NCT ID:
NCT05455619
Status:
RECRUITING
Last Update Posted:
2024-05-22
First Post:
2022-06-22
Brief Title:
Evexomostat Plus PI3K or AKT Inhibitor and Fulvestrant in Women With a PI3K Alteration and HRHer2- Breast Cancer
Sponsor:
SynDevRx Inc
Organization:
SynDevRx Inc
Study Overview
Official Title:
Study to Assess the Safety and Efficacy of Evexomostat SDX-7320 in Combination With A PI3K or Akt Inhibitor Plus Fulvestrant in Patients With HR HER2- Metastatic Breast Cancer With PI3K Pathway Alterations
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Amelia-1
Brief Summary:
This is a Phase 1b2 open-label parallel-arms pilot study in post-menopausal women with hormone receptor positive HR HER2- advanced or metastatic breast cancer with an alteration in the PI3K pathway including a mutation of the PIK3CA gene PTEN loss or AKT1 mutation designed to determine the safety of evexomostat SDX-7320 plus standard of care treatment alpelisib BYL-719 or capivasertib and fulvestrant each combined the triplet therapy to measure the severity and number of hyperglycemic events and to assess clinical anti-tumor benefit of the triplet therapy
The purpose of this study is
to characterize the safety of the triplet drug combination consisting of either alpelisib or capivasertib per the treating oncologists choice and fulvestrant plus evexomostat
to test whether evexomostat when given in combination with either alpelisib or capivasertib and fulvestrant will reduce the number and severity of hyperglycemic events andor reduce the number or dose of anti-diabetic medications needed to control the hyperglycemia for metabolically normal patients and those deemed at risk for capivasertib and alpelisib-induced hyperglycemia insulin resistance as measured by HOMA-IR baseline elevated HbA1c or well-controlled type 2 diabetes and
to assess preliminary anti-tumor efficacy for each combination and changes in key biomarkers and quality of life in this patient population
The purpose of this study is
to characterize the safety of the triplet drug combination consisting of either alpelisib or capivasertib per the treating oncologists choice and fulvestrant plus evexomostat
to test whether evexomostat when given in combination with either alpelisib or capivasertib and fulvestrant will reduce the number and severity of hyperglycemic events andor reduce the number or dose of anti-diabetic medications needed to control the hyperglycemia for metabolically normal patients and those deemed at risk for capivasertib and alpelisib-induced hyperglycemia insulin resistance as measured by HOMA-IR baseline elevated HbA1c or well-controlled type 2 diabetes and
to assess preliminary anti-tumor efficacy for each combination and changes in key biomarkers and quality of life in this patient population
Detailed Description:
Phosphoinositide 3-kinase PI3K pathway alterations frequently occur in breast cancer conferring growth advantages to cancer cells via increased catalytic activity of various related proteins such as protein kinase B AKT or via the loss of function of the negative regulator phosphatase and tensin homolog PTEN He 2021 Of these alterations the PIK3CA gene is most frequently mutated leading to disease aggressiveness and patient mortality Currently approved treatments targeting this pathway include alpelisib a small molecule that inhibits the activity of the PIK3CA gene product PI3Kα and capivasertib a small molecule that targets the AKT protein Both molecules have demonstrated similar clinical benefit in cancer patients with genetic alterations that activate the PI3KAkt mammalian target of rapamycin mTOR pathway André 2019 Turner 2023 However hyperglycemia a toxicity associated with PI3K andor Akt inhibition leads to hyperinsulinemia re-activating the pathway and thereby limiting each drugs clinical efficacy Management of hyperglycemia is important to ensure patients receive optimal anti-tumor therapy Rugo 2020 Restoring insulin sensitivity and reducing levels of insulin have been suggested as ways to blunt the hyperglycemia associated with drugs that inhibit this pathway and have been reported to improve their efficacy Hopkins 2018 Crouthamel 2009
The purpose of this study is
to characterize the safety of the triplet drug combination consisting of either alpelisib or capivasertib per the treating oncologists choice and fulvestrant plus evexomostat
to test whether evexomostat when given in combination with either alpelisib or capivasertib and fulvestrant will reduce the number and severity of hyperglycemic events andor reduce the number or dose of anti-diabetic medications needed to control the hyperglycemia for metabolically normal patients and those deemed at risk for capivasertib and alpelisib-induced hyperglycemia insulin resistance as measured by HOMA-IR baseline elevated HbA1c or well-controlled type 2 diabetes and
to assess preliminary anti-tumor efficacy for each combination and changes in key biomarkers and quality of life in this patient population
This is a Phase 1b2 open-label parallel-arms pilot study in post-menopausal women with hormone receptor positive HR HER2- advanced or metastatic breast cancer with an alteration in the PI3K pathway including a mutation of the PIK3CA gene PTEN loss or AKT1 mutation designed to determine the safety of evexomostat SDX-7320 plus standard of care treatment alpelisib BYL-719 or capivasertib and fulvestrant each combined the triplet therapy to measure the severity and number of hyperglycemic events and to assess clinical anti-tumor benefit of the triplet therapy
The study will consist of a 14-day pre-treatment phase of evexomostat plus fulvestrant starting on C1D1 before adding either alpelisib or capivasertib on C1D15 The Triple Therapy treatment schedule is summarized in the following table Tumor assessments will be conducted as a function of when the triplet therapy starts
Up to 52 patients for each combination arm may be enrolled starting with dose-escalation cohorts of up to 6 patients for each combination arm Once the maximum tolerated dose MTD of the triplet therapy has been defined for each combination additional patients will be enrolled until a total of up to 20 patients have completed at least two cycles of the triplet therapy at that dose and combination If warranted up to an additional 20 patients may be enrolled to further characterize the safety profile andor anti-tumor effect of each triplet therapy
The planned escalation scheme starts at an evexomostat dose of 36 mgm2 one dose below the monotherapy MTD of 49 mgm2 in combination with either alpelisib or capivasertib and fulvestrant given at the marketed doses Based on aggregate safety data from the first two cycles of the first 6 patients across each triplet combination and in the absence of 2 dose-limiting toxicities DLTs as defined herein the Safety Review Committee SRC in consultation with the Sponsor and the Investigators may increase the evexomostat dose for the next cohort to 49 mgm2 In the presence of 2 DLTs the SRC may decrease the evexomostat dose to 27 mgm2 and may adjust the dose of either alpelisib or capivasertib if warranted The dose of fulvestrant will not be adjusted If the evexomostat dose of 49 mgm2 is determined by the SRC not to be tolerable in combination with either alpelisib or capivasertib and fulvestrant then current and future patients for only their respective combination treatment will receive evexomostat at 36 mgm2
Patients will remain on study for up to 7 cycles to characterize the safety and tolerability of the triplet therapy as well as to capture initial efficacy data eg progression-free survival PFS following 6 months of the triplet therapy Patients will be allowed to continue on the triplet therapy if they are receiving clinical benefit including stable disease as determined by their treating oncologist
The purpose of this study is
to characterize the safety of the triplet drug combination consisting of either alpelisib or capivasertib per the treating oncologists choice and fulvestrant plus evexomostat
to test whether evexomostat when given in combination with either alpelisib or capivasertib and fulvestrant will reduce the number and severity of hyperglycemic events andor reduce the number or dose of anti-diabetic medications needed to control the hyperglycemia for metabolically normal patients and those deemed at risk for capivasertib and alpelisib-induced hyperglycemia insulin resistance as measured by HOMA-IR baseline elevated HbA1c or well-controlled type 2 diabetes and
to assess preliminary anti-tumor efficacy for each combination and changes in key biomarkers and quality of life in this patient population
This is a Phase 1b2 open-label parallel-arms pilot study in post-menopausal women with hormone receptor positive HR HER2- advanced or metastatic breast cancer with an alteration in the PI3K pathway including a mutation of the PIK3CA gene PTEN loss or AKT1 mutation designed to determine the safety of evexomostat SDX-7320 plus standard of care treatment alpelisib BYL-719 or capivasertib and fulvestrant each combined the triplet therapy to measure the severity and number of hyperglycemic events and to assess clinical anti-tumor benefit of the triplet therapy
The study will consist of a 14-day pre-treatment phase of evexomostat plus fulvestrant starting on C1D1 before adding either alpelisib or capivasertib on C1D15 The Triple Therapy treatment schedule is summarized in the following table Tumor assessments will be conducted as a function of when the triplet therapy starts
Up to 52 patients for each combination arm may be enrolled starting with dose-escalation cohorts of up to 6 patients for each combination arm Once the maximum tolerated dose MTD of the triplet therapy has been defined for each combination additional patients will be enrolled until a total of up to 20 patients have completed at least two cycles of the triplet therapy at that dose and combination If warranted up to an additional 20 patients may be enrolled to further characterize the safety profile andor anti-tumor effect of each triplet therapy
The planned escalation scheme starts at an evexomostat dose of 36 mgm2 one dose below the monotherapy MTD of 49 mgm2 in combination with either alpelisib or capivasertib and fulvestrant given at the marketed doses Based on aggregate safety data from the first two cycles of the first 6 patients across each triplet combination and in the absence of 2 dose-limiting toxicities DLTs as defined herein the Safety Review Committee SRC in consultation with the Sponsor and the Investigators may increase the evexomostat dose for the next cohort to 49 mgm2 In the presence of 2 DLTs the SRC may decrease the evexomostat dose to 27 mgm2 and may adjust the dose of either alpelisib or capivasertib if warranted The dose of fulvestrant will not be adjusted If the evexomostat dose of 49 mgm2 is determined by the SRC not to be tolerable in combination with either alpelisib or capivasertib and fulvestrant then current and future patients for only their respective combination treatment will receive evexomostat at 36 mgm2
Patients will remain on study for up to 7 cycles to characterize the safety and tolerability of the triplet therapy as well as to capture initial efficacy data eg progression-free survival PFS following 6 months of the triplet therapy Patients will be allowed to continue on the triplet therapy if they are receiving clinical benefit including stable disease as determined by their treating oncologist
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None