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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 (INAVO121)

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ClinicalTrials.gov Identifier: NCT05646862
Recruitment Status : Recruiting
First Posted : December 12, 2022
Last Update Posted : April 25, 2024
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Inavolisib Drug: Fulvestrant Drug: Alpelisib Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 7, 2023
Estimated Primary Completion Date : March 30, 2029
Estimated Study Completion Date : March 30, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arms and Interventions
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Arm Intervention/treatment
Experimental: Inavolisib + Fulvestrant
Participants will be administered the treatments as outlined in the interventions section.
 Drug: 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.

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

Drug: 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.


Outcome Measures
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Primary Outcome Measures :
  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) ]

Secondary Outcome Measures :
  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 ]
  5. BICR-Assessed Duration of Response (DOR) [ Time Frame: From CR or PR until disease progression or death due to any cause (up to approximately 64 months) ]
  6. Time to Confirmed Deterioration (TTCD) in Pain [ Time Frame: 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. ]
  7. TTCD in Physical Functioning [ Time Frame: 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. ]
  8. TTCD in Role Functioning [ Time Frame: 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. ]
  9. TTCD in Global Health Status/Quality of Life (QOL) [ Time Frame: 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. ]
  10. Percentage of Participants with Adverse Events [ Time Frame: Day 1 until 30 days after the final dose of study treatment (up to approximately 85 months) ]
  11. Plasma Concentration of Inavolisib at Specified Timepoints [ Time Frame: Day 1 and 15 of Cycle 1, and Day 1 of Cycles 2 and 3. Each cycle is 28 days. ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05646862


Contacts
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Contact: Reference Study ID Number: WO43919 https://forpatients.roche.com/ 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05646862    
Other Study ID Numbers: WO43919
2022-502322-41-00 ( Registry Identifier: EU Clinical Trials )
First Posted: December 12, 2022    Key Record Dates
Last Update Posted: April 25, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Inavolisib
Antineoplastic Agents, Hormonal
Antineoplastic Agents
 Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Phosphoinositide-3 Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action