Ignite Creation Date:
2024-05-06 @ 3:52 PM
Last Modification Date:
2024-10-26 @ 1:59 PM
Study NCT ID:
NCT04789096
Status:
RECRUITING
Last Update Posted:
2024-06-21
First Post:
2021-03-01
Brief Title:
Tucatinib Together With Pembrolizumab and Trastuzumab
Sponsor:
Breast Cancer Trials Australia and New Zealand
Organization:
Breast Cancer Trials Australia and New Zealand
Study Overview
Official Title:
A Phase II Two-arm Non-comparative Multicentre Study of Tucatinib ONT-380 Pembrolizumab and Trastuzumab in Patients With Pre-treated Advanced HER2-positive Breast Cancer
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:
TUGETHER
Brief Summary:
Women or men with HER2-positive metastatic breast cancer who have progressed on previous treatment will receive tucatinib in combination with pembrolizumab and trastuzumab PD-L1 positive
Detailed Description:
Despite significant advances in systemic treatment options advanced HER2-positive breast cancer post treatment with trastuzumab pertuzumab and T-DM1 still remains incurable with brain metastases remaining a major cause of patient morbidity and mortality
HER2-positive breast cancers have relatively high tumour infiltrating lymphocytes TILs that may be targeted with immune checkpoint blockade Studies in metastatic breast cancer with PD1 or PD-L1 inhibition have shown an overall survival OS benefit for those that are enriched for pre-existing immunity such as positive expression of PD-L1 protein or TILs present
One of the main areas of disease progression in HER2 positive disease is in the central nervous system CNS supporting the need to find an effective combination for patients with brain metastases
Tucatinib ONT-380 is a potent highly selective oral HER2 small molecule tyrosine kinase inhibitor TKI with demonstrated clinical benefit notable for its minimal inducement of EGFR-type toxicities when administered in combination-type studies including proven intra-cranial efficacy in studies of patients with brain metastases
The investigators hypothesise that the combination of tucatinib with trastuzumab and PD-1 inhibition will result in a similar ORR as that seen in HER2CLIMB along with comparable PFS and duration of response particularly through prevention and treatment of CNS metastases The potential advantage of adding PD-1 inhibition and omitting capecitabine in the PD-L1 positive group is to increase the durability of the response with hopefully less added toxicity for patients The investigators believe this regimen will result in comparable outcomes as those seen in HER2CLIMB with fewer adverse events Importantly the side effect profiles of all agents in our proposed combination are non-overlapping and this combination provides a unique opportunity for excellent tolerability and durable disease control in this patient group The study design initially included two treatment cohorts with the PD-L1 negativeunknown cohort being treated with the HER2CLIMB regimen with the addition of pembrolizumab MK-3475 under the hypothesis that the anti-tumour activity of this regimen will overcome the lower immunogenicity of this subgroup However Protocol Amendment 2 will omit capecitabine in the PD-L1 negativeunknown cohort due to a high frequency of liver test abnormalities within the first seven participants in this cohort
HER2-positive breast cancers have relatively high tumour infiltrating lymphocytes TILs that may be targeted with immune checkpoint blockade Studies in metastatic breast cancer with PD1 or PD-L1 inhibition have shown an overall survival OS benefit for those that are enriched for pre-existing immunity such as positive expression of PD-L1 protein or TILs present
One of the main areas of disease progression in HER2 positive disease is in the central nervous system CNS supporting the need to find an effective combination for patients with brain metastases
Tucatinib ONT-380 is a potent highly selective oral HER2 small molecule tyrosine kinase inhibitor TKI with demonstrated clinical benefit notable for its minimal inducement of EGFR-type toxicities when administered in combination-type studies including proven intra-cranial efficacy in studies of patients with brain metastases
The investigators hypothesise that the combination of tucatinib with trastuzumab and PD-1 inhibition will result in a similar ORR as that seen in HER2CLIMB along with comparable PFS and duration of response particularly through prevention and treatment of CNS metastases The potential advantage of adding PD-1 inhibition and omitting capecitabine in the PD-L1 positive group is to increase the durability of the response with hopefully less added toxicity for patients The investigators believe this regimen will result in comparable outcomes as those seen in HER2CLIMB with fewer adverse events Importantly the side effect profiles of all agents in our proposed combination are non-overlapping and this combination provides a unique opportunity for excellent tolerability and durable disease control in this patient group The study design initially included two treatment cohorts with the PD-L1 negativeunknown cohort being treated with the HER2CLIMB regimen with the addition of pembrolizumab MK-3475 under the hypothesis that the anti-tumour activity of this regimen will overcome the lower immunogenicity of this subgroup However Protocol Amendment 2 will omit capecitabine in the PD-L1 negativeunknown cohort due to a high frequency of liver test abnormalities within the first seven participants in this cohort
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?:
True
Is an FDA AA801 Violation?:
None