To Study the Effect of Inavolisib in Combination with Fulvestrant in Participants with Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Feb 2026 → ongoing

Decision date (initial)

2026-01-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy and safety of inavolisib 9 mg once a day (QD) in combination with fulvestrant compared with inavolisib 6 mg QD in combination with fulvestrant

Secondary objectives 2

1. To evaluate the efficacy of inavolisib 9 mg QD in combination with fulvestrant compared with inavolisib 6 mg QD in combination with fulvestrant
2. To evaluate the safety and tolerability of inavolisib 9 mg QD in combination with fulvestrant compared with inavolisib 6 mg QD in combination with fulvestrant

Conditions and MedDRA coding

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA)-Mutated, hormone receptor-positive (HR-Positive), human epidermal growth factor receptor 2 (HER2)-Negative Locally Advanced or Metastatic Breast Cancer

Regulatory references

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Documented ER+ or PR+ tumor, per ASCO/CAP guidelines
2. Documented HER2-negative tumor, per ASCO/CAP guidelines
3. Disease progression during or after treatment with a combination of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) in the metastatic setting – Participants must have received no more than one prior line of systemic therapy in the locally advanced (recurrent or progressed) or metastatic setting
4. Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) – Participants with evaluable bone-only disease are not eligible; disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft tissue component per RECIST v1.1 may be eligible
5. Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated (e.g., participants with visceral crisis) at time of entry into the study, as per national or local treatment guidelines
6. Confirmation of biomarker eligibility: presence of ≥ 1 study-eligible PIK3CA mutation
7. Life expectancy of > 6 months
8. Ability, in the investigator’s judgment, and willingness to comply with all study -related procedures, including completion of patient-reported outcomes

Exclusion criteria 6

1. Metaplastic breast cancer
2. Prior treatment with chemotherapy in the recurrent locally advanced/metastatic setting
3. Type 1 diabetes, or Type 2 diabetes requiring ongoing systemic therapy
4. Prior treatment with PI3K/Akt/mTOR inhibitors in the recurrent locally advanced/metastatic setting
5. Symptomatic active lung disease, including pneumonitis
6. Requirement for daily supplemental oxygen

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Confirmed Objective Response Rate (ORR), defined as the proportion of participants with a complete response or partial response on at least two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1
2. Incidence of key inavolisib-associated adverse events, including hyperglycemia, stomatitis/oral mucositis, and diarrhea.
3. Severity of key PI3K-inhibition associated adverse events, including hyperglycemia, stomatitis/oral mucositis, and diarrhea as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Secondary endpoints 9

1. DOR, duration of response, defined as the time from the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
2. TTR, time to response, defined as the time from randomization to first occurrence of a documented objective response as determined by the investigator according to RECIST v1.1
3. PFS, progression-free survival, defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first)
4. Incidence of treatment discontinuations due to adverse events
5. Change from baseline in targeted clinical laboratory test results
6. Presence, frequency of occurrence, severity, and/or degree of interference with daily activities of symptomatic treatment toxicities (i.e., diarrhea, nausea, vomiting, decreased appetite, fatigue, mouth sores, and rash), as assessed through use of the National Cancer Institute Patient-Reported outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) instrument
7. Presence and frequency of occurrence of selected hyperglycemia symptoms (i.e. increased thirst and frequent urination), as assessed through the European Organisation for Research and Treatment of Cancer (EORTC) IL382
8. Proportion of participants reporting each response option at each assessment timepoint by treatment arm for treatment side effect bother single-item General Population Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General questionnaire (FACT-G)
9. Change from baseline/worsening in symptomatic treatment toxicities and treatment side effect bother as assessed through use of the PRO-CTCAE, EORTC IL382, and FACT-G GP5 item, respectively

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 6

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications