Study assessing the efficacy and safety of alpelisib plus fulvestrant or letrozole, based on prior endocrine therapy, in patients with PIK3CA mutation with advanced breast cancer who have progressed on or after prior treatments

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

2 Oct 2017 → 13 Nov 2024

Decision date (initial)

2024-03-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-509167-24-00

EudraCT number

2016-004586-67

ClinicalTrials.gov

NCT03056755

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the proportion of patients who are alive without disease progression at 6 months based on local investigator assessment per RECIST v1.1 separately in cohorts A and C (alpelisib in combination with fulvestrant) and cohort B (alpelisib in combination with letrozole) among patients with HR+, HER2-negative aBC harboring a PIK3CA mutation who have progressed on or after prior treatments

Secondary objectives 7

1. To assess PFS based on local investigator assessment for each cohort
2. To assess PFS on next-line treatment (PFS2) for each cohort
3. To assess overall response rate (ORR) and clinical benefit rate (CBR) based on local investigator assessment for each cohort
4. To assess duration of response (DOR) in patients with confirmed complete response (CR) or PR for each cohort
5. To assess Overall Survival (OS) for each cohort
6. To evaluate the safety and tolerability of the combination for each cohort
7. Evaluate clinical benefit as assessed by the Investigator during the Extension Phase

Conditions and MedDRA coding

Adult patients with PIK3CA mutant, HR-positive, HER2-negative advanced breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patient is an adult male or female ≥ 18 years old
2. Patient has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory. It is recommended to provide a tumor sample collected after the most recent progression or recurrence
3. Advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy
4. Patient has been confirmed as PIK3CA mutant as determined by a certified designated laboratory
5. Patient has histologically and/or cytologically confirmed ER+ and/ or PgR+ BC
6. Patient has confirmed, HER2-negative aBC. HER2-negative defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+
7. Patients must be diagnosed with aBC, with documented evidence of tumor progression on or after prior treatments. No more than one prior regimen of chemotherapy for the treatment of metastatic disease is permitted. The maximum number of prior therapies for aBC or mBC is limited to two (maintenance therapies, where applicable, must be regarded as part of the main therapy). Patients must have recovered to grade 1 or better from any adverse events (except alopecia) related to previous therapy prior to study entry
8. Patient has either measurable disease, i.e. at least one measurable lesion as per RECIST v1.1 criteria or if no measurable disease is present than at least one predominantly lytic bone lesion must be present
9. Patient has ECOG performance status of ≤ 2
10. Patient has adequate bone marrow function

Exclusion criteria 9

1. Patient has received prior treatment with any PI3K inhibitors
2. Patients with an established diagnosis of diabetes mellitus type I or uncontrolled type II (based on FG and HbA1c in inclusion criterion 11)
3. Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated basal or squamous cell carcinoma, nonmelanoma skin cancer or curatively resected cervical cancer
4. Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia)
5. Patients receiving systemic corticosteroids ≤ 2 weeks prior to treatment with alpelisib
6. History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis
7. Patient has impaired GI function or GI disease that may affect the absorption of study drugs
8. Patient has documented pneumonitis
9. Patients being concurrently treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme Cytochrome P (CYP)3A within the last 5 days prior to study entry

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study is the proportion of patients who are alive without disease progression at 6 months based on local investigator assessment using RECIST v1.1 in each cohort

Secondary endpoints 7

1. PFS based on local investigator assessment using RECIST v1.1 in each cohort
2. PFS2 based on local investigator assessment in each cohort
3. ORR based on local investigator’s assessment according to RECIST v1.1 in each cohort Clinical Benefit Rate (CBR) based on local investigator’s assessment according to RECIST v1.1 in each cohort
4. Duration of Response is the time from the date of first documented response (confirmed CR or PR) to the date of first documented progression or death
5. Overall Survival is defined as the time of start of treatment to date of death or lost to follow-up
6. Type, frequency and severity of adverse events per CTCAE v4.03 Type, frequency and severity of laboratory toxicities per CTCAE v4.03
7. Proportion of patients with clinical benefit as assessed by the Investigator at scheduled visits

Investigational products

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

Test 6

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 7

Locations

2 EU/EEA countries · 2 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 30 files

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

Application history

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