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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05646862




Registration number
NCT05646862
Ethics application status
Date submitted
2/12/2022
Date registered
12/12/2022
Date last updated
23/05/2024

Titles & IDs
Public title
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
Scientific title
A Phase III, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Versus Alpelisib Plus Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Who Progressed During or After CDK4/6 Inhibitor and Endocrine Combination Therapy
Secondary ID [1] 0 0
2022-502322-41-00
Secondary ID [2] 0 0
WO43919
Universal Trial Number (UTN)
Trial acronym
INAVO121
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Inavolisib
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Alpelisib

Experimental: Inavolisib + Fulvestrant - Participants will be administered the treatments as outlined in the interventions section.

Active Comparator: Alpelisib + Fulvestrant - Participants will be administered the treatments as outlined in the interventions section.


Treatment: Drugs: Inavolisib
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.

Treatment: Drugs: Fulvestrant
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.

Treatment: Drugs: Alpelisib
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS)
Timepoint [1] 0 0
From randomization until disease progression or death due to any cause (up to approximately 64 months)
Secondary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
From randomization until death due to any cause (up to approximately 85 months)
Secondary outcome [2] 0 0
BICR-Assessed Overall Response Rate (ORR)
Timepoint [2] 0 0
Up to approximately 64 months
Secondary outcome [3] 0 0
BICR-Assessed Best Overall Response (BOR)
Timepoint [3] 0 0
Up to approximately 64 months
Secondary outcome [4] 0 0
BICR-Assessed Clinical Benefit Rate (CBR)
Timepoint [4] 0 0
Up to approximately 64 months
Secondary outcome [5] 0 0
BICR-Assessed Duration of Response (DOR)
Timepoint [5] 0 0
From CR or PR until disease progression or death due to any cause (up to approximately 64 months)
Secondary outcome [6] 0 0
Time to Confirmed Deterioration (TTCD) in Pain
Timepoint [6] 0 0
Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
Secondary outcome [7] 0 0
TTCD in Physical Functioning
Timepoint [7] 0 0
Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
Secondary outcome [8] 0 0
TTCD in Role Functioning
Timepoint [8] 0 0
Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
Secondary outcome [9] 0 0
TTCD in Global Health Status/Quality of Life (QOL)
Timepoint [9] 0 0
Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
Secondary outcome [10] 0 0
Percentage of Participants with Adverse Events
Timepoint [10] 0 0
Day 1 until 30 days after the final dose of study treatment (up to approximately 85 months)
Secondary outcome [11] 0 0
Plasma Concentration of Inavolisib at Specified Timepoints
Timepoint [11] 0 0
Day 1 and 15 of Cycle 1, and Day 1 of Cycles 2 and 3. Each cycle is 28 days.

Eligibility
Key inclusion criteria
- 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

- Disease progression after or during treatment with a combination of CDK4/6i and
endocrine therapy: <= 2 prior lines of systemic therapy in mBC setting; CDK4/6i based
therapy does not need to be the last one received prior study entry; one line of
chemotherapy in mBC setting allowed

- Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors
version 1.1 (RECIST v1.1)

- Participants for whom endocrine-based therapy is recommended and treatment with
cytotoxic chemotherapy is not indicated at time of entry into the study, as per
national or local treatment guidelines

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

- Life expectancy of > 6 months

- Adequate hematologic and organ function prior to initiation of study treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

- Pregnant, lactating, or breastfeeding, or intending to become pregnant during the
study or at least 60 days after the final dose of study treatment

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

- Inability or unwillingness to swallow pills

- Malabsorption syndrome or other condition that would interfere with enteral absorption

- Any history of leptomeningeal disease or carcinomatous meningitis

- Known and untreated, or active central nervous system (CNS) metastases. Participants
with a history of treated CNS metastases are eligible if they meet specific certain
criteria

- Known active, systemic infection at study enrollment, or any major episode of
infection requiring treatment with intravenous antibiotics or hospitalization within 7
days prior to Day 1 of Cycle 1

- Any concurrent ocular or intraocular condition that, in the opinion of the
investigator, would require medical or surgical intervention during the study period
to prevent or treat vision loss that might result from that condition

- Active inflammatory or infectious conditions in either eye or history of idiopathic or
autoimmune-associated uveitis in either eye

- Requirement for daily supplemental oxygen

- Symptomatic active lung disease, including pneumonitis

- History of or active inflammatory bowel disease

- Any active bowel inflammation

- Clinically significant and active liver disease, including severe liver impairment,
viral or other hepatitis, current alcohol abuse, or cirrhosis

- Participants with known human immunodeficiency virus infection that meet specific
criteria

- Investigational drug(s) within 4 weeks before randomization or within 5 half-lives of
the investigational drug(s), whichever is longer

- History of other malignancy within 5 years prior to screening, except for cancers with
very low risk of recurrence

- Chronic therapy of >= 10 mg of prednisone per day or an equivalent dose of other
anti-inflammatory corticosteroids or immunosuppressants for a chronic disease

- Allergy or hypersensitivity to components or excipients of the inavolisib,
fulvestrant, or alpelisib formulations

- History of severe cutaneous reactions like Stevens-Johnson Syndrome, Erythema
Multiforme, Toxic Epidermal Necrolysis, or Drug Reaction with Eosinphilia and Systemic
Symptoms

- Active ongoing osteonecrosis of the jaw

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/06/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/03/2029
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Campbelltown Hospital; Macarthur Cancer Therapy Centre - Campbelltown
Recruitment hospital [2] 0 0
Coffs Harbour Health Campus - Coffs Harbour
Recruitment hospital [3] 0 0
Concord Repatriation General Hospital; Concord Cancer Centre - Concord
Recruitment hospital [4] 0 0
Kinghorn Cancer Centre; St Vincents Hospital - Darlinghurst
Recruitment hospital [5] 0 0
Gosford Hospital; Cancer Care Services - Gosford
Recruitment hospital [6] 0 0
Icon Cancer Care Wesley - Auchenflower
Recruitment hospital [7] 0 0
University of the Sunshine Coast - Sippy Downs
Recruitment hospital [8] 0 0
Bendigo Cancer Centre - Bendigo
Recruitment hospital [9] 0 0
Sir Charles Gairdner Hospital; Medical Oncology - Perth
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment postcode(s) [2] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [3] 0 0
2139 - Concord
Recruitment postcode(s) [4] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 0 0
2250 - Gosford
Recruitment postcode(s) [6] 0 0
4066 - Auchenflower
Recruitment postcode(s) [7] 0 0
4556 - Sippy Downs
Recruitment postcode(s) [8] 0 0
3550 - Bendigo
Recruitment postcode(s) [9] 0 0
6009 - Perth
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05646862
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: WO43919 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. Only)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05646862