Health Trials

A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy

ConditionBreast Cancer
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorHoffmann-La Roche

About this trial

This is a Phase III, multicenter, randomized, open-label, global study designed to evaluate the efficacy and safety of inavolisib plus fulvestrant compared with alpelisib plus fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) -negative, PIK3CA-mutated, locally advanced (LA) or metastatic breast cancer (mBC), who progressed during or after cyclin dependent kinase 4/6i (CDK4/6i)-based therapy.

Enrollment for the main study is now complete.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

If pre/perimenopausal women and men treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy beginning at least 2 weeks prior to Day 1 of Cycle 1

Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent

Documented HR +/ HER2- tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines

Confirmation of biomarker eligibility: detection of specified mutation(s) of PIK3CA via specified test

Disqualifiers

Metaplastic breast cancer

Prior treatment in locally advanced or metastatic setting with any PI3K, AKT, or mTOR inhibitor or any agent whose mechanism of action is to inhibit the PI3K/-AKT/-mTOR pathway

Participant who relapsed with documented evidence of progression > 12 months from completion of adjuvant CDK4/6i based therapy with no treatment for metastatic disease

Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes

Trial design

Design model

Parallel

Treatments tested in this trial

  • Inavolisib

    Drug

    Participants will be administered a 9 milligram (mg) inavolisib tablet orally once a day (PO QD) on Days 1-28 of each 28-day cycle of main study and sub-study.

  • Fulvestrant

    Drug

    Participants will be administered 500 mg of fulvestrant on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent 28-day cycle of main study and sub-study.

  • Alpelisib

    Drug

    Alpelisib will be administered to participants at the approved dose in combination with fulvestrant: 300 mg taken PO QD and on days 1-28 of each 28-day cycle.

  • Bupropion

    Drug

    Participants will be administered bupropion PO on Day -3 and Day 12 of Cycle 1 of the sub-study.

  • Omeprazole

    Drug

    Participants will be administered omerprazole PO on Day -4 and Day 11 of Cycle 1 of sub-study.

  • Midazolam

    Drug

    Participants will be administered midazolam PO on Day -4 and Day 11 of Cycle 1 of sub-study.

Treatment groups

420 Participants
are divided into 3 treatment groups
Group A: Inavolisib + FulvestrantExperimental treatment 2 interventions
Group B: Alpelisib + FulvestrantActive comparator 2 interventions
Group C: Sub-study: Inavolisib + Fulvestrant + CYP substratesExperimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS)

Time frame
From randomization until disease progression or death due to any cause (up to approximately 64 months)
2

Sub-study: Maximum observed Drug Concentration (Cmax) for Midazolam

Time frame
Day -4 and -3 of Cycle (C) 1, Day (D) 11 and C1D12. A cycle is 28 days.
3

Sub-study: Cmax for Bupropion

Time frame
Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
4

Sub-study: Cmax for Omeprazole

Time frame
Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.

Secondary outcomes

1

Overall survival (OS)

Time frame
From randomization until death due to any cause (up to approximately 85 months)
2

BICR-Assessed Overall Response Rate (ORR)

Time frame
Up to approximately 64 months
3

BICR-Assessed Best Overall Response (BOR)

Time frame
Up to approximately 64 months
4

BICR-Assessed Clinical Benefit Rate (CBR)

Time frame
Up to approximately 64 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Hoffmann-La Roche

Lead sponsor

Source ClinicalTrials.gov
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