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

Summary

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.

Conditions

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

Interventions

DRUG

Giredestrant

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

DRUG

Abemaciclib

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

DRUG

Ipatasertib

400 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression

DRUG

Inavolisib

9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression

DRUG

Ribociclib

600 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression

DRUG

Everolimus

10 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression

DRUG

Samuraciclib

360 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression

DRUG

PH FDC SC

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.

DRUG

Palbociclib

125 mg orally once a day on Days 1-21 during each 28-day cycle until unacceptable toxicity or disease progression

DRUG

Atezolizumab

840 mg by intravenous (IV) infusion on Days 1 and 15 each 28-day cycle.

Sponsors & Collaborators

• Hoffmann-La Roche

  lead INDUSTRY

Principal Investigators

• Clinical Trials · Hoffmann-La Roche

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-22

Primary Completion

2029-05-30

Completion

2029-05-30

FDA Drug

Yes

Countries

• United States
• Australia
• Israel
• South Korea
• Spain

Study Locations