Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
110
Countries
2
Sites
15
Early-Stage, PIK3CA-Mutated Breast Cancer (BC)
To evaluate the safety and tolerability of inavolisib-based treatment combination(s)
Key facts
- Sponsor
- F. Hoffmann-La Roche AG
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 30 Sep 2025 → ongoing
- Decision date (initial)
- 2025-07-01
- 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: Efficacy, Others, Safety
To evaluate the safety and tolerability of inavolisib-based treatment combination(s)
Secondary objectives 2
- To evaluate the efficacy of inavolisib-based treatment combination(s)
- To evaluate the tolerability from the participant perspective of inavolisib-based treatment combination(s)
Conditions and MedDRA coding
Early-Stage, PIK3CA-Mutated Breast Cancer (BC)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10073254 | Neoadjuvant therapy | 100000004865 |
| 20.0 | PT | 10006187 | Breast cancer | 100000004864 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | OPEN-LABEL, MULTICENTER STUDY INAVOLISIB TREATMENTS IN PATIENTS WITH EARLY-STAGE
|
Randomised Controlled | None | A: Inavolisib, Ribo, Letrozole B: Inavolisib, Letrozole C: Ribociclib, Letrozole |
Regulatory references
- Plan to share IPD
- No
- IPD plan description
- N/A
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-508124-36-00 | A Phase I, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0077 as a Single Agent in Patients with Locally Advanced or Metastatic PIK3CA-Mutant Solid Tumors and in combination with Endocrine and Targeted Therapies in Patients with Locally Advanced or Metastatic PIK3CA -Mutant Breast Cancer | Genentech Inc. |
| 2023-505812-39-00 | A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients with PIK3CA -Mutant, Hormone Receptor-Positive, HER2 -Negative Locally Advanced or Metastatic Breast Cancer | F. Hoffmann-La Roche AG |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Histologically confirmed operable or inoperable invasive Stage II-III BC according to American Joint Committee on Cancer (AJCC) TNM staging classification
- Candidate for neoadjuvant treatment and considered appropriate for endocrine combination therapy
- Willingness to undergo breast surgery (mastectomy or breast-conserving surgery) after neoadjuvant treatment (unless inoperable)
- Documented ER-positive tumor in accordance with current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, assessed locally and defined as ≥ 1% of tumor cells stained positive for ER
- Documented HER2-negative tumor in accordance with current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, assessed locally
- Documented Ki-67 score ≥ 5% as per local assessment
- Confirmed PIK3CA mutation, as documented through central laboratory testing of a representative formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample
Exclusion criteria 6
- Stage IV (metastatic) breast cancer
- Inflammatory breast cancer (cT4d)
- Bilateral invasive breast cancer
- History of ductal carcinoma in situ or lobular carcinoma in situ if they have received any systemic therapy for treatment or radiation therapy to the ipsilateral breast
- Previous systemic or local treatment for the primary BC currently under investigation (including excisional biopsy or any other surgery of the primary tumor and/or axillary lymph nodes, including sentinel lymph node biopsy, radiotherapy, cytotoxic, and endocrine treatments)
- Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0 grading scale
- Change from baseline in selected clinical laboratory test results
- Tolerability, as assessed by the overall treatment exposure and the incidence of dose modifications and treatment discontinuation due to adverse events
Secondary endpoints 6
- Pathologic Complete Response (pCR) rate in breast and axilla (ypT0/Tis ypN0) according to local pathologist assessment following the American Joint Committee on Cancer (AJCC) TNM staging system (Amin et al. 2017; NCCN 2024)
- Tumor overall objective response rate (ORR)
- Changes in Ki-67 by immunohistochemistry (IHC)
- Presence, frequency of occurrence, severity, and/or degree of interference with daily function of selected symptomatic treatment toxicities as assessed through use of the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)
- Proportion of participants reporting each response option at each assessment timepoint for treatment side-effect bother single-item General Population, Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General (FACT-G)
- Change from baseline/worsening in symptomatic treatment toxicities and treatment side-effect bother as assessed through use of PRO-CTCAE and the FACT-G GP5 item
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 9
SUB08444MIG · Substance
- Active substance
- Letrozole
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 2.5 mg milligram(s)
- Max total dose
- 402.5 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for clinical trial use.
SUB08444MIG · Substance
- Active substance
- Letrozole
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 2.5 mg milligram(s)
- Max total dose
- 402.5 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for clinical trial use.
LETROZOLE ACCORD HEALTHCARE 2,5 mg, comprimé pelliculé
PRD4609615 · Product
- Active substance
- Letrozole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 2.5 mg milligram(s)
- Max total dose
- 402.5 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02BG04 — LETROZOLE
- Marketing authorisation
- 34009 394 393 7 2
- MA holder
- ACCORD HEALTHCARE FRANCE SAS
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for clinical trial use.
Letrozol STADA® 2,5 mg Filmtabletten
PRD389191 · Product
- Active substance
- Letrozole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 2.5 mg milligram(s)
- Max total dose
- 402.5 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02BG04 — LETROZOLE
- Marketing authorisation
- 68973.00.00
- MA holder
- STADAPHARM GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for clinical trial use.
SUB180246 · Substance
- Active substance
- Ribociclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 50.4 g gram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for clinical trial use.
Kisqali 200 mg film-coated tablets
PRD5341551 · Product
- Active substance
- Ribociclib
- Substance synonyms
- LEE011
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 50.4 g gram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EF02 — -
- Marketing authorisation
- EU/1/17/1221/005
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for clinical trial use.
SUB180246 · Substance
- Active substance
- Ribociclib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 50.4 g gram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabeled for clinical trial use.
PRD9793132 · Product
- Active substance
- Inavolisib
- Other product name
- GDC-0077
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 9 mg milligram(s)
- Max total dose
- 1449 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- F. HOFFMANN-LA ROCHE LTD
- Paediatric formulation
- No
- Orphan designation
- No
PRD9793811 · Product
- Active substance
- Inavolisib
- Other product name
- GDC-0077
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 9 mg milligram(s)
- Max total dose
- 1449 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- F. HOFFMANN-LA ROCHE LTD
- Paediatric formulation
- No
- Orphan designation
- No
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 7
| Organisation | City, country | Duties |
|---|---|---|
| CellCarta ORG-100039881
|
Antwerp, Belgium | Laboratory analysis |
| IQVIA Limited ORG-100008655
|
Reading, United Kingdom | Other |
| Labcorp Early Development Laboratories Inc. ORG-100012865
|
Madison, United States | Laboratory analysis |
| FACIT.Org Inc. ORG-100048771
|
Ponte Vedra, United States | Other |
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Laboratory analysis |
| Axon Communications Inc. ORG-100048038
|
Toronto, Canada | Other |
| Perceptive Informatics Inc. ORG-100013171
|
Billerica, United States | Interactive response technologies (IRT) |
Locations
2 EU/EEA countries · 15 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ongoing, recruiting | 16 | 8 |
| Spain | Ongoing, recruitment ended | 18 | 7 |
| Rest of world
Korea, Republic of, Brazil, Canada, United States, Argentina
|
— | 76 | — |
Investigational sites
HELIOS Kliniken Schwerin GmbH
Frauenklinik, Wismarsche Strasse 393-397, 19049, Schwerin
St. Vincenz-Krankenhaus GmbH
Frauen- und Kinderklinik St. Louise, Husener Strasse 81, Kernstadt, Paderborn
HELIOS Klinikum Berlin-Buch GmbH
Klinik für Geburtshilfe und Gynäkologie, Schwanebecker Chaussee 50, Buch, Berlin
Technische Universitaet Dresden
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Fetscherstrasse 74, Johannstadt-Nord, Dresden
KEM I Evang. Kliniken Essen-Mitte gGmbH
Klinik für Senologie/Brustzentrum, Henricistrasse 92, Huttrop, Essen
DBZ Onkologie GmbH
N.A., Hoenower Strasse 31-33, Mahlsdorf, Berlin
National Center For Tumor Diseases (NCT) Heidelberg
Sektion Gynäkologische Onkologie, Im Neuenheimer Feld 460, Neuenheim, Heidelberg
Philipps-Universitaet Marburg
Klinik für Gynäkologie und Geburtshilfe, Baldingerstrasse, 35043, Marburg
Hospital Universitario De Salamanca
Oncology, Paseo De San Vicente 58-182, 37007, Salamanca
Hospital Clinic De Barcelona
Oncology, Calle Villarroel 170, 08036, Barcelona
Hospital General Universitario Gregorio Maranon
Oncology, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Universitari Vall D Hebron
Oncology, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Hospital Universitario Virgen De La Macarena
Oncology, Avenida Del Doctor Fedriani 3, 41009, Sevilla
Hospital Clinico Universitario De Valencia
Oncology, Avenida Blasco Ibanez 17, 46010, Valencia
Hospital Universitario 12 De Octubre
Oncology, Avenida De Cordoba Sn, 28041, Madrid
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Germany | 2026-01-15 | 2026-02-02 | |||
| Spain | 2025-09-30 | 2025-10-24 | 2026-03-06 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 15 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | d1_protocol-2024-518811-20-00-redacted | 2 |
| Protocol (for publication) | d4_patient-facing-documents_memo | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_BO45853 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_IAF | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_MAIN_BO45853_Redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_MAIN_BO45853_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Patient_BO45853 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_RBR_BO45853_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_RBR_BO45853_redacted | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc letrozole | NA |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-letrozole | NA |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-ribociclib | NA |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_eng-2024-518811-20-00 | 1.0 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_es-2024-518811-20-00 | 1.0 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-04-23 | Germany | Acceptable 2025-07-01
|
2025-07-01 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-07-28 | Germany | Acceptable | 2025-08-01 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-09-11 | Germany | Acceptable 2025-10-16
|
2025-10-16 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-11-27 | Germany | Acceptable 2026-02-24
|
2026-02-27 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-03-10 | Germany | Acceptable 2026-02-24
|
2026-03-10 |
| 6 | SUBSTANTIAL MODIFICATION | SM-4 | 2026-03-13 | Germany | Acceptable | 2026-03-18 |