The SAPPHO Study: A Single-Arm, Phase II Study of Sequential Therapy With Curative Intent in de Novo HER2+ Metastatic Breast Cancer

Registration Number
NCT06439693
Lead Sponsor
Dana-Farber Cancer Institute
Brief Summary

The purpose of this study is to test the safety and effectiveness of a sequence of drugs (a Taxane plus Trastuzumab plus Pertuzumab followed by Trastuzumab Deruxtecan, followed by Tucatinib plus Ado-Trastuzumab Emtansine (T-DM1), followed by Trastuzumab plus Pertuzumab plus Tucatinib) in HER2+ Breast Cancer. The study will help investigators understand wheth...

Detailed Description

This is an open-label phase II single-arm study to test the efficacy of a regimen of human epidermal growth factor receptor 2 (HER2)-targeted study drugs in participants with HER2-Positive metastatic Breast Cancer (HER2+ MBC).
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Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
72
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
HER2+ Breast CancerNab-PaclitaxelParticipants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
HER2+ Breast CancerPhesgoParticipants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
HER2+ Breast CancerTrastuzumab Subcutaneous SubcutaneousParticipants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
HER2+ Breast CancerPaclitaxelParticipants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
HER2+ Breast CancerDocetaxelParticipants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
HER2+ Breast CancerT-DM1Participants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
HER2+ Breast CancerPertuzumabParticipants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
HER2+ Breast CancerTrastuzumab DeruxtecanParticipants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
HER2+ Breast CancerTrastuzumabParticipants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
HER2+ Breast CancerTucatinibParticipants will complete: * Screening visit with tumor biopsy and imaging. * Imaging on Day I of cycles for Parts A through D. * Part A: * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (or biosimilar) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab 1X daily * Predetermined dose of Taxane (Paclitaxel, Docetaxel, or Nab-Paclitaxel) * Part B: --Day 1 of 21 day cycle: Predetermined dose of trastuzumab deruxtecan 1X daily * Part C: * Day 1 of 21 day cycle: Predetermined dose of T-DM1 1X daily * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Part D: * Imaging every 9 weeks * Days 1 through 21 of 21 day cycle: Predetermined dose of Tucatinib 2X daily * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab (biosimilar or SC) 1X daily * Day 1 of 21 day cycle: Predetermined dose of Pertuzumab (or PHESGO) 1X daily * Follow Up: visits every 12 weeks with imaging every 9 weeks.
Primary Outcome Measures
NameTimeMethod
Disease Free Survival at 4 Years (DFS4)Up to 4 years

DFS4 is the probability estimate 4 years based on Kaplan-Meier Method. DFS is defined the time from registration to disease progression (including death from any cause) or resumption of anti-cancer therapy (not including endocrine therapy). Participants that are alive, progression free and off all anti-cancer therapy are censored at the date of their last di...

Secondary Outcome Measures
NameTimeMethod
Non-Completion reasons of each part of the sequential therapyUp to 54 months

Sequential therapy includes (A) taxane, trastuzumab, pertuzumab, (B) trastuzumab deruxtecan, (C) ado-trastuzumab emtansine, tucatinib, and (D) trastuzumab, pertuzumab, tucatinib. The reasons of non-completion will be tabulated.

Complete Rate of Each Treatment PartUp to 54 months

Sequential therapy includes (A) taxane, trastuzumab, pertuzumab, (B) trastuzumab deruxtecan, (C) ado-trastuzumab emtansine, tucatinib, and (D) trastuzumab, pertuzumab, tucatinib. The proportion of participants who complete each part of therapy will be tabulated as the complete rate.

DFS4 by Minimal Residual Disease (MRD) statusUp to 4 years

DFS4 is defined as primary outcome 1. Participants will be categorized by MRD status (detectable nv non-detectable).

Objective Response Rate (ORR)Up to 54 months

Objective response rate (ORR), defined as best overall response of either complete or partial response, will be assessed among participants who start protocol therapy and have measurable disease at screening. Radiographic response will be assessed using RECIST 1.1 criteria as defined in section 11.1. The objective response rate by RECIST 1.1 (CR + PR) will b...

Grade 3-5 Treatment-Related Toxicity RateUp to 54 months

The percentage of participants who experienced a maximum grade 3-5 treatment-related adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.

Median Overall Survival (OS)Up to 5 years

Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.

Trial Locations

Locations (1)

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

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