A clinical study to assess the efficacy of alpelisib plus fulvestrant in participants with HR-positive, HER2-negative, advanced breast cancer after treatment with a CDK4/6 inhibitor and an aromatase inhibitor

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Nov 2021 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-509133-39-00

EudraCT number

2021-001966-39

ClinicalTrials.gov

NCT05038735

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Safety, Efficacy

To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to treatment with placebo plus fulvestrant

Secondary objectives 7

1. To determine whether treatment with alpelisib plus fulvestrant prolongs overall survival (OS) compared to treatment with placebo plus fulvestrant
2. To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria
3. To evaluate the association between PIK3CA mutation status as measured in circulating tumor deoxyribonucleic acid (ctDNA) at baseline with PFS upon treatment with alpelisib
4. To assess safety and tolerability of alpelisib in combination with fulvestrant compared to placebo in combination with fulvestrant
5. To evaluate treatment with alpelisib plus fulvestrant compared to placebo plus fulvestrant, with respect to time to deterioration of Eastern Cooperative Oncology Group (ECOG) performance status
6. To evaluate patient-reported outcomes of alpelisib plus fulvestrant compared to placebo and fulvestrant
7. To explore the long-term benefit intermediate to PFS and OS

Conditions and MedDRA coding

Hormone receptor positive, HER2-negative advanced breast cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant is an adult ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines.
2. Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory.
3. Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is required by local laboratory testing.
4. Participant has at least one measurable lesion as per RECIST v1.1 criteria as assessed by Investigator (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation).
5. Participant has recurrence or progression of disease during or after combined AI (i.e. letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combined AI and CDK4/6 inhibitor therapy does not need to be the latest treatment regimen (including adjuvant setting).
6. Participant has received ≤2 prior lines of systemic therapies overall in the metastatic setting, of which a maximum of 1 line of prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy) is permitted.
7. The presence of PIK3CA mutation(s) determined in tumor tissue prior to enrollment either by a Novartis designated laboratory or in tumor tissue or plasma ctDNA by a local laboratory using a Food and Drug Administration (FDA)-approved PIK3CA Companion Diagnostics (CDx) test for alpelisib or the CE-IVD QIAGEN Therascreen® PIK3CA RGQ PCR test.
8. If female, then the participant must be in postmenopausal status

Exclusion criteria 3

1. Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy (ET) per the investigator's best judgment.
2. Participant who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine/endocrine-based therapy with no treatment for metastatic disease
3. Participant has received prior treatment with fulvestrant, any oral selective estrogen receptor degrader (SERD), any Phosphatidylinositol-3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria

Secondary endpoints 7

1. Overall survival
2. Overall response rate (ORR) with confirmed response, clinical benefit rate (CBR) with confirmed response, duration of response (DOR) with confirmed response, and time to response (TTR) based on BIRC assessment and RECIST v1.1
3. PFS based on BIRC assessment and using RECIST v1.1 criteria for participants by PIK3CA mutation status assessed in ctDNA at baseline
4. Incidence, type and severity of adverse events per CTCAE v4.03 criteria
5. Time to definitive deterioration of ECOG performance status from baseline
6. Time to definitive (10%) deterioration in the global health status/Quality of Life (QoL) and symptom scale scores of the EORTC QLQ-C30 Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30
7. Time from randomization to objective tumour progression on next line treatment or death from any cause (PFS2)

Investigational products

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

Test 2

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 10

Locations

16 EU/EEA countries · 89 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 160 files

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

Application history

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