A Study Evaluating the Efficacy and Safety of Inavolisib Plus Palbociclib and Fulvestrant versus Placebo Plus Palbociclib and Fulvestrant in Patients with PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic 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

28 Aug 2020 → ongoing

Decision date (initial)

2024-07-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-505812-39-00

EudraCT number

2019-002455-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Others, Safety

To evaluate the efficacy of inavolisib plus palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant on the basis of progression-free survival

Secondary objectives 4

1. To evaluate the efficacy of inavolisib plus palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant on the basis of overall survival, objective response rate; best overall response rate; duration of response; clinical benefit rate; and time to confirmed deterioration in pain, physical function, role function, and global health status (GHS)/health-related quality of life (HRQoL)
2. To evaluate the safety of inavolisib plus palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant on the basis of incidence and severity of adverse events, and changes from baseline in: targeted vital signs, clinical laboratory test results, and electrocardiogram (ECG) parameters
3. To characterize the pharmacokinetics (PK) of inavolisib, palbociclib, and fulvestrant, when administered in combination in this population on the basis of their plasma concentrations
4. To characterize the PK of inavolisib at additional timepoints in patients enrolled in China

Conditions and MedDRA coding

HR+/HER2-Negative Locally Advanced or Metastatic Breast cancer with PIK3CA mutation

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Confirmed diagnosis of HR+/HER2-negative breast cancer
2. Metastatic or Locally Advanced disease not amenable to curative therapy
3. Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
4. Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
5. Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

Exclusion criteria 6

1. Metaplastic breast cancer
2. Any history of leptomeningeal disease or carcinomatous meningitis
3. Any prior systemic therapy for metastatic breast cancer
4. Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of patients that have received fulvestrant or any selective estrogen receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months
5. Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
6. 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 1

1. 1. Progression-free survival

Secondary endpoints 17

1. 1. Overall survival
2. 2. Objective response rate
3. 3. Best overall response rate
4. 4. Clinical benefit rate
5. 5. Duration of response
6. 6. Time to confirmed deterioration (TTCD) in pain
7. 7. TTCD in physical function
8. 8. TTCD in Role Function
9. 9. TTCD in GHS/HRQoL
10. 10. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
11. 11. Change from baseline in targeted vital signs
12. 12. Change from baseline in targeted clinical laboratory test results
13. 13. Change from baseline in ECG parameters
14. 14. Plasma concentration of inavolisib at specified timepoints
15. 15. Plasma concentration of inavolisib at additional specified timepoints in patients enrolled in China
16. 16. Plasma concentration of palbociclib at specified timepoints
17. 17. Plasma concentration of fulvestrant at specified timepoints

Investigational products

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

Test 8

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 15

Locations

9 EU/EEA countries · 44 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 112 files

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

Application history

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