Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype (HARMONIA)

• ClinicalTrials.gov Identifier: NCT05207709
• Recruitment Status: Recruiting
• First Posted: January 26, 2022
• Last Update Posted: June 23, 2023
• Sponsor: SOLTI Breast Cancer Research Group
• Collaborators: Novartis; Alliance Foundation Trials, LLC.
• Information provided by (Responsible Party): SOLTI Breast Cancer Research Group

Tracking Information

• First Submitted Date: January 4, 2022
• First Posted Date: January 26, 2022
• Last Update Posted Date: June 23, 2023
• Actual Study Start Date: March 28, 2022
• Estimated Primary Completion Date: March 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 12, 2022)

Progression-free survival [ Time Frame: From date of randomization until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled ]

using RECIST 1.1 criteria, as assessed by local radiologists/investigators

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 12, 2022)

• Progression-free survival 2 [ Time Frame: From randomization until documented progression to second line of therapy, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled ]
  defined as the time from randomization to first documented progression on next-line therapy or death, whichever occurs first
• Overall Survival [ Time Frame: until patient death, assessed up to approximately 62 months after the first patient enrolled ]
  the proportion of exitus patients
• Overall response and clinical benefit [ Time Frame: until disease progression or 24 weeks from treatment start. ]
  defined as percentage of patients with CR, PR per RECIST 1.1 or SD lasting 24 weeks or longer, as defined by RECIST 1.1.
• Time to response and duration of response [ Time Frame: time from treatment start to response and time from response to disease progression, assessed up to approximately 62 months after the first patient enrolled ]
  defined per RECIST 1.1
• Adverse events (safety) [ Time Frame: from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled ]
  Occurrence /severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype
• Official Title: A Phase III, Multicenter, Open-label Study of Ribociclib vs. Palbociclib in Patients With Advanced Hormone Receptor-positive/HER2-negative/HER2-Enriched Breast Cancer - HARMONIA Trial

Brief Summary

HARMONIA is an international, multicenter, randomized, open-label and phase III study. The primary objective of this study is to demonstrate that the combination of ribociclib with endocrine therapy (letrozole or fulvestrant) is superior to palbociclib with endocrine therapy (letrozole or fulvestrant) in prolonging progression-free survival in patients with advanced HR+/HER2- and HER2-E breast cancer. The study will enroll approximately 456 patients with HER2-E disease from approximately 95 sites worldwide.

In addition, the HARMONIA trial will include an exploratory cohort of patients with HR+/HER2- and Basal-like disease treated with paclitaxel +/- Tislelizumab. This cohort does not have a predefined sample size and the objective is only exploratory, given the suggested lack of efficacy of the combinations of hormone therapy and CDK4/6 inhibitors in this subgroup of patients. Enrolment into the basal-like cohort will stop once the HER2-E disease cohort is fully enrolled.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Breast Cancer

Intervention

• Drug: Ribociclib + Letrozole OR Fulvestrant
  Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
• Drug: Palbociclib + Letrozole OR Fulvestrant
  Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
• Drug: Paclitaxel +/- Tislelizumab
  Patients in this arm could receive as the first line of therapy

Study Arms

• Experimental: Ribociclib + Endocrine Therapy
  Ribociclib + Fulvestrant or Letrozole
  Intervention: Drug: Ribociclib + Letrozole OR Fulvestrant
• Experimental: Palbociclib + Endocrine Therapy
  Palbociclib + Fulvestrant or Letrozole
  Intervention: Drug: Palbociclib + Letrozole OR Fulvestrant
• Experimental: Paclitaxel +/- Tislelizumab - Exploratory cohort
  Additional experimental Cohort that includes patients with Basal-Like intrinsic subtype.
  Intervention: Drug: Paclitaxel +/- Tislelizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 12, 2022): 456
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 1, 2027
• Estimated Primary Completion Date: March 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Main Inclusion Criteria:

• Histologically documented HR-positive and HER2-negative breast cancer by local testing
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
• Availability of FFPE tumor block for biomarker analysis, obtained during metastatic period.
• HER2-E or Basal-like subtype as per central PAM50 analysis.
• Measurable disease or non-measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end-organ function
• Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
• Women of childbearing potential must have confirmed negative serum pregnancy test within 7 days prior to randomization.
• Women of CBP must be willing to use highly effective methods of contraception.

• Patient must have a 6-lead or 12-lead ECG with ALL of the following parameters at screening:

  • QTcF interval (QT interval using Fridericia's correction) at screening < 450 msec.
  • Resting heart rate 50-90 beats per minute (determined from the ECG).

Main Exclusion Criteria:

• Prior therapy with any CDK4/6 inhibitors.
• Patient has received prior treatment with chemotherapy for advanced/metastatic breast cancer

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Juan M Ferrero-Cafiero, PharmD; 606819182; juan.ferrero@gruposolti.org

• Listed Location Countries: Portugal, Spain, United States

Administrative Information

• NCT Number: NCT05207709
• Other Study ID Numbers: SOLTI-2101; 2021-002027-38 ( EudraCT Number ); LEE011A2303R ( Other Identifier: Novartis ); AFT-58 ( Other Identifier: Alliance Foundation Trials, LLC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: SOLTI Breast Cancer Research Group
• Original Responsible Party: Same as current
• Current Study Sponsor: SOLTI Breast Cancer Research Group
• Original Study Sponsor: Same as current

Collaborators

• Novartis
• Alliance Foundation Trials, LLC.

Investigators

• Principal Investigator: Aleix Prat, MD; Hospital Clínic of Barcelona / SOLTI
• Principal Investigator: Lisa A Carey, MD; UNC Lineberger Comprehensive Cancer Center
• Principal Investigator: Dan G Stover, MD; Stefanie Spielman Comprehensive Breast Center
• Principal Investigator: Tomás Pascual, MD; Hospital Clínic of Barcelona / SOLTI cancer research group

• PRS Account: SOLTI Breast Cancer Research Group
• Verification Date: June 2023