A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer

Conditions

• Inoperable, Locally Advanced or Metastatic, ER-positive Breast Cancer

Eligibility Criteria

Sex

FEMALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Giredestrant — DRUG
  30 milligrams (mg) orally once a day (during each 28-day cycle or 21-day cycle, depending on the regimen) until unacceptable toxicity or disease progression
• Abemaciclib — DRUG
  150 mg orally twice a day (during each 28-day cycle or 21-day cycle, depending on the regimen) until unacceptable toxicity or disease progression
• Ipatasertib — DRUG
  400 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression
• Inavolisib — DRUG
  9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
• Ribociclib — DRUG
  600 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression
• Everolimus — DRUG
  10 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
• Samuraciclib — DRUG
  360 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
• PH FDC SC — DRUG
  On Day 1 of Cycle 1 (1 cycle is 21 days), pertuzumab and trastuzumab fixed-dose combination for subcutaneous use (PH FDC SC) will be administered SC as a fixed dose formulation of 1200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase. On Day 1 of Cycles 2 and beyond, PH FDC SC will be administered SC once every 21 days as a fixed dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase.
• Palbociclib — DRUG
  125 mg orally once a day on Days 1-21 during each 28-day cycle until unacceptable toxicity or disease progression
• Atezolizumab — DRUG
  840 mg by intravenous (IV) infusion on Days 1 and 15 each 28-day cycle.

Study Details

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with breast cancer. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the patient population. Cohort 1 will focus on participants with inoperable, locally advanced or metastatic, estrogen receptor-positive (ER+), HER2-negative breast cancer who had disease progression during or following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; e.g., palbociclib, ribociclib, abemaciclib) in the first- or second-line setting. Cohort 2 will focus on inoperable, locally advanced or metastatic, ER+, HER2-positive breast cancer with previous progression to standard-of-care anti-HER2 therapies, of which one was a trastuzumab-and-taxane-based systemic therapy (including in the early setting if recurrence occurred within 6 months of finishing adjuvant therapy) and one was a HER2-targeting antibody-drug conjugate (ADC; e.g., ado-trastuzumab emtansine or trastuzumab-deruxtecan) or a HER2-targeting tyrosine kinase inhibitor (TKI; e.g., tucatinib, lapatinib, pyrotinib, or neratinib). Cohort 3 will focus on inoperable, locally advanced or metastatic, ER+, HER2-negative, PIK3CA-mutated breast cancer with resistance to adjuvant endocrine therapy.

Key Dates

Start date

Jun 22, 2021

Status verified

Jun 2026

Primary completion

May 30, 2029

Completion

May 30, 2029

Study Design

Enrollment

316 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Cohort 1: Giredestrant Monotherapy
• Experimental: Cohort 1: Giredestrant + Abemaciclib
• Experimental: Cohort 1: Giredestrant + Ipatasertib
• Experimental: Cohort 1: Giredestrant + Inavolisib
• Experimental: Cohort 1: Giredestrant + Ribociclib
• Experimental: Cohort 1: Giredestrant + Everolimus
• Experimental: Cohort 1: Giredestrant + Samuraciclib
• Experimental: Cohort 1: Giredestrant + Atezolizumab
• Experimental: Cohort 1: Giredestrant + Abemaciclib + Atezolizumab
• Experimental: Cohort 1: Giredestrant + Inavolisib (ESR1m enriched)
  ESR1m stands for estrogen receptor mutation.
• Active Comparator: Cohort 2: Giredestrant + PH FDC SC
• Experimental: Cohort 2: Giredestrant + PH FDC SC + Abemaciclib
• Experimental: Cohort 2: Giredestrant + PH FDC SC + Palbociclib
• Experimental: Cohort 3: Giredestrant + Inavolisib + Palbociclib
• Experimental: Cohort 3: Giredestrant + Inavolisib + Abemaciclib
• Experimental: Cohort 3: Giredestrant + Inavolisib + Ribociclib

Primary Outcome Measure

Percentage of Participants with Objective Response, Defined as a Complete or Partial Response, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) [ Time Frame: From Baseline until disease progression (up to 6 years) ]

Central Contacts

• Reference Study ID Number: CO42867 https://forpatients.roche.com/
  888-662-6728 (U.S. Only)
  [email protected]
• Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Locations (12)

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