Study to assess the efficacy and safety of alpelisib in combination with olaparib in participants with platinum-resistant or refractory gBRCAnm HGSOC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Oct 2021 → 20 Jan 2026

Decision date (initial)

2024-05-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2024-510782-42-00

EudraCT number

2019-004682-40

ClinicalTrials.gov

NCT04729387

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Therapy

To determine whether treatment with alpelisib in combination with olaparib prolongs PFS compared to single agent cytotoxic chemotherapy in participants with platinum resistant/refractory, gBRCAnm HGSOC

Secondary objectives 6

1. To determine whether treatment with alpelisib in combination with olaparib prolongs OS compared to single agent cytotoxic chemotherapy in participants with platinum-resistant or refractory, gBRCAnm HGSOC
2. To assess safety and tolerability of alpelisib in combination with olaparib when administered to participants with platinum-resistant or refractory, gBRCAnm HGSOC
3. To evaluate alpelisib in combination with olaparib compared to single agent cytotoxic chemotherapy in participants with platinum-resistant or refractory, gBRCAnm HGSOC with respect to time to deterioration of ECOG (Eastern Cooperative Oncology Group) performance status
4. To assess additional efficacy parameters
5. To characterize the PK of alpelisib and olaparib when administered in combination in patients with platinum-resistant or refractory, gBRCAnm HGSOC
6. To evaluate patient reported-outcomes of alpelisib in combination with olaparib compared to single agent cytotoxic chemotherapy in adult participants with platinum-resistant or refractory, gBRCAnm HGSOC

Conditions and MedDRA coding

Platinum-resistant or refractory, high-grade serous ovarian cancer with no germline BRCA mutation

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 has histologically confirmed diagnosis of high-grade serous or high-grade endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
2. Measurable disease, i.e., at least one measurable lesion per RECIST 1.1 criteria (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)
3. If no measurable disease is present, the disease should be assessable by Gynecologic Cancer Intergroup criteria (GCIC) for CA-125
4. Participant has no germline BRCA1/2 mutation as determined by an FDA-approved assay
5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Participant has platinum-resistant (progression within one to six months after completing platinum-based therapy) or platinum refractory disease (progression during treatment or within 4 weeks after the last dose), where platinum-based therapy is not an option, according to the GCIG 5th Ovarian Cancer Consensus Conference definitions. The platinum-based chemotherapy regimen does not necessarily need to be the last regimen the participant received prior to study entry.
7. Participant must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment
8. Participant has received prior bevacizumab or is not eligible to receive bevacizumab due to medical reasons

Exclusion criteria 10

1. Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor
2. Participant is concurrently using other anti-cancer therapy
3. Participant is in a state of small or large bowel obstruction or has other impairment of gastrointestinal (GI) function or GI disease
4. Participant has had surgery within 14 days prior to starting study drug or has not recovered from major adverse effects
5. Participant has not recovered from all toxicities related to prior anticancer therapies to baseline or NCI CTCAE Version 4.03 Grade ≤1. Exception to this criterion: participants with any grade of alopecia are allowed to enter the study
6. Participant has an established diagnosis of diabetes mellitus type I or uncontrolled type II based on fasting plasma glucose and HbA1c
7. Participants with liver impairment and Child Pugh score B or C
8. Participant has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to randomization, and who has not recovered to baseline, grade 1 or better from related adverse effects of such therapy (with the exception of alopecia)
9. Participant has a known hypersensitivity to any of the study drugs or excipients
10. Participant has a history of myelodysplastic syndrome or acute myeloid leukemia, or presents clinical and/ or laboratory features suggestive thereof

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS based on BIRC assessment using RECIST 1.1 criteria

Secondary endpoints 6

1. OS
2. Safety: Incidence, type and severity of adverse events per CTCAE v4.03 criteria including changes in laboratory values, vital signs, hepatic, renal and cardiac assessments. Tolerability: dose interruptions, reductions, dose intensity and duration of exposure for all drug components.
3. Time to definitive deterioration of the ECOG performance status from baseline
4. 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 using RECIST 1.1 criteria)
5. Summary of statistics of PK parameters (including but not limited to AUCtau, AUClast, Cmax, Tmax) of alpelisib and olaparib (full PK subset only), Summary of statistics of plasma alpelisib and olaparib concentrations by time point.
6. Change from baseline in Function Assessment of Cancer Therapy-Ovarian Trial Outcome Index (FACT-O)

Investigational products

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

Test 4

Comparator 2

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

3 EU/EEA countries · 7 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 14 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