Safety and Efficacy of T-DXd vs. CDK4/6i-based ET as First-line Therapy of HR-positive and HER2-low/Ultralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype
NCT Number: NCT06486883
Acronym: PONTIAC
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Advanced Breast Cancer|Advanced Breast Carcinoma|Hormone Receptor Positive Breast Carcinoma
Interventions: DRUG: Trastuzumab deruxtecan (T-DXd, DS-8201a)|DRUG: CDK4/6i plus ET
Sponsor: MedSIR
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 200
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12
Completion Date: 2028-01

Summary:
This trial studies a type of advanced breast cancer defined as hormone receptor HR-positive/HER2-negative and classified as non-luminal by gene expression profiling (PAM50). Patients will be treated with trastuzumab deruxtecan (T-DXd) or with physician's choice of CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET). The main purpose of the study is to analyze the efficacy of T-DXd in patients who have HR-positive and HER2-low/ultralow advanced breast cancer classified as non-luminal subtype.

Primary Outcome Measures: Progression-free survival (PFS), PFS, defined as the period from randomization date to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1. in HER2-low patients., Up to 25 months|Progression-free survival (PFS), PFS, defined as the period from randomization date to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1 in all patients., Up to 25 months
Secondary Outcome Measures: Overall survival (OS), OS, defined as the period from randomization date to death from any cause, as determined locally by the investigator (in all patients and HER2-low population)., Up to 25 months|Objective response rate (ORR), ORR, defined as the rate of patients with complete response (CR) or partial response (PR), as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population)., Up to 25 months|Clinical benefit rate (CBR), CBR, defined as the rate of patients with objective response (CR or PR), or stable disease for at least 24 weeks, as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population)., Up to 25 months|Duration of response (DoR), DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population)., Up to 25 months|Time to response (TTR), TTR, defined as the period from randomization date to the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR, as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population)., Up to 25 months|Time to treatment failure (TTF), TTF, defined as the time from randomization date to discontinuation of treatment for any reason, including progressive disease, treatment toxicity, patient choice, and death., Up to 25 months|Time to first subsequent chemotherapy (TFSC), TFSC, defined as the time from randomization date to the beginning of the first subsequent chemotherapy after discontinuation of the trial regimen., Up to 25 months|Progression free survival 2 (PFS2), PFS2, defined as the time from randomization to objective tumor progression on next-line treatment or death from any cause, in each treatment arm., Up to 25 months|Time to start of first subsequent therapy or death (TFST), TFST, defined as the time from randomization to the earliest date of anti-cancer therapy start date following study treatment discontinuation, or death., Up to 25 months|Best percentage of change in tumor burden, Best percentage of change from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, as determined locally by the investigator using RECIST v.1.1., Up to 25 months|Health-related quality-of-life (HRQoL), Changes in health-related quality-of-life (HRQoL) from baseline using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)., Up to 25 months|Health-related quality-of-life (HRQoL), Changes in health-related quality-of-life (HRQoL) from baseline using the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR42)., Up to 25 months|Health-related quality-of-life (HRQoL), Changes in health-related quality-of-life (HRQoL) from baseline using the EuroQol 5-level EQ-5D version (EQ-5D-5L) index., Up to 25 months|Incidence of Adverse Events, Serious Adverse Events and Suspected Unexpected Serious Adverse Reactions, Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Suspected Unexpected Serious Adverse Reactions (SUSARs) according to the National Cancer Institute (NCI) CTCAE Version 5.0 (v.5.0) (Safety and Tolerability), Up to 25 months