Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected

NCT04729387 | Terminated Phase 3 DMC FDA Drug

• 2 other identifiers: CBYL719K123012024-510782-42-00
• Study Type: interventional
• Target: 358
• Locations: 25 countries
• Sites: 90

Brief Summary

The objective of this study is to assess the efficacy and safety of the combination of alpelisib and olaparib compared with single agent cytotoxic chemotherapy in patients with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected.

Conditions

Ovarian Cancer

Keywords

Alpelisib; olaparib; paclitaxel; pegylated liposomal doxorubicin; high grade; serous ovarian; fallopian or peritoneal cancer; no germline BRCA mutation; BRCA wild type; platinum-resistant or refractory; prior PARP inhibitor exposure; EPIK-O

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment using RECIST 1.1 criteria

  Progression-free survival (PFS) was defined as the time from randomization until the first documented disease progression or death from any cause, based on BIRC assessment. Participants without an event were censored at the date of their last adequate tumor assessment. Clinical deterioration without objective radiologic evidence was not considered disease progression in the primary efficacy analysis.

  From randomization until the date of the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 23 months

Secondary Outcomes (13)

• Overall survival

  From randomization until death, assessed up to approximately 44 months

• Overall Response Rate (ORR) with confirmed response based on BIRC assessment according to RECIST 1.1 criteria

  Up to approximately 23 months

• Clinical benefit rate (CBR) with confirmed response based on BIRC assessment according to RECIST 1.1

  Up to approximately 23 months

• Time to response (TTR) based on BIRC assessment and according to RECIST 1.1

  From the date of randomization to the first documented response, assessed through Month 12

• Duration of response (DOR) with confirmed response based on BIRC assessment and according to RECIST 1.1

  From first documented response to first documented progression or death, assessed up to approximately 23 months

Study Arms (2)

Alpelisib+olaparib

EXPERIMENTAL

Alpelisib 200 mg orally once daily and olaparib 200 mg orally twice daily on a continuous dosing schedule.

Drug: Alpelisib; Drug: Olaparib

Paclitaxel or PLD

ACTIVE COMPARATOR

Investigator's choice of one of 2 single agent cytotoxic chemotherapies: Paclitaxel 80 mg/m2 intravenously weekly or Pegylated liposomal Doxorubicin (PLD) 40-50 mg/m2 (physician discretion) intravenously every 28 days.

Drug: Paclitaxel; Drug: Pegylated liposomal doxorubicin (PLD)

Interventions

Pegylated liposomal doxorubicin (PLD) DRUG

PLD will be administered at 40-50 mg/m2 (physician discretion) as an intravenous infusion once every 28-days in a 28 day treatment cycle, starting on Cycle 1 Day 1

Paclitaxel or PLD

Alpelisib DRUG

Alpelisib will be administered at 200 mg orally once daily following food on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle

Also known as: BYL719

Alpelisib+olaparib

Olaparib DRUG

Olaparib will be administered at 200 mg orally twice daily irrespective of meals on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle.

Alpelisib+olaparib

Paclitaxel DRUG

Paclitaxel will be administered at 80 mg/m2 as an intravenous infusion weekly during a 28-day treatment cycle, starting on Cycle 1 Day 1, and on Day 8, Day 15 and Day 22 of every cycle thereafter

Paclitaxel or PLD

Eligibility Criteria

• Age: 18 Years - 100 Years
• Gender Eligibility Details: Adult women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has histologically confirmed diagnosis of high-grade serous or high-grade endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
• 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)
• If no measurable disease is present, the disease should be assessable by Gynecologic Cancer Intergroup criteria (GCIC) for CA-125
• Participant has no germline BRCA1/2 mutation as determined by an FDA-approved assay
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• 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 (Wilson et al 2016). The platinum-based chemotherapy regimen does not necessarily need to be the last regimen the participant received prior to study entry
• 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
• Participant has received prior bevacizumab or is not eligible to receive bevacizumab due to medical reasons.

You may not qualify if:

• Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor
• Participant is concurrently using other anti-cancer therapy
• Participant is in a state of small or large bowel obstruction or has other impairment of gastrointestinal (GI) function or GI disease
• Participant has had surgery within 14 days prior to starting study drug or has not recovered from major adverse effects
• 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
• Participant has an established diagnosis of diabetes mellitus type I or uncontrolled type II based on fasting plasma glucose and HbA1c
• Participants with liver impairment and Child Pugh score B or C
• 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)
• Participant has a known hypersensitivity to any of the study drugs or excipients
• Participant has a history of myelodysplastic syndrome or acute myeloid leukemia, or presents clinical and/ or laboratory features suggestive thereof.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (93)

Arizona Oncology Associates

Phoenix, Arizona, 85016, United States

Location

HonorHealth

Phoenix, Arizona, 85016, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

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Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

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Maryland Oncology Hematology P A

Silver Spring, Maryland, 20904, United States

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Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

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Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

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Memorial Sloan Kettering Cancer Ctr

New York, New York, 10065, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

University Of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57106, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

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Texas Oncology P A

Bedford, Texas, 76022, United States

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Texas Oncology

Dallas, Texas, 75246, United States

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Texas Oncology P A

San Antonio, Texas, 78217, United States

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Texas Oncology Northeast Texas

Tyler, Texas, 75702, United States

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Novartis Investigative Site

CABA, Buenos Aires, C1125ABD, Argentina

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Novartis Investigative Site

Buenos Aires, C1012AAR, Argentina

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Novartis Investigative Site

Caba, C1015ABO, Argentina

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Novartis Investigative Site

Bedford Park, South Australia, 5041, Australia

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Novartis Investigative Site

Shepparton, Victoria, 3630, Australia

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Novartis Investigative Site

Sydney, 2031, Australia

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Innsbruck, Tyrol, 6020, Austria

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Graz, 8036, Austria

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Brussels, 1000, Belgium

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Leuven, 3000, Belgium

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Novartis Investigative Site

Namur, 5000, Belgium

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Belo Horizonte, Minas Gerais, 30130-100, Brazil

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São Paulo, São Paulo, 04014-002, Brazil

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Calgary, Alberta, T2N 5G2, Canada

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Vancouver, British Columbia, V5Z 4E6, Canada

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London, Ontario, N6A 5W9, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Chengdu, Sichuan, 610041, China

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Beijing, 100036, China

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Jinan, 250012, China

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Shanghai, 200032, China

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Tianjin, 300480, China

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Ostrava, Poruba, 708 52, Czechia

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Nový Jičín, 741 01, Czechia

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Prague, 128 08, Czechia

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Herlev, DK-2730, Denmark

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Odense C, 5000, Denmark

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Kuopio, FIN-70211, Finland

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Tampere, FIN-33521, Finland

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Turku, FIN 20521, Finland

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Besançon, 25030, France

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Lyon, 69373, France

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Paris, 75012, France

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Pierre-Bénite, 69495, France

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Villejuif, 94800, France

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Mannheim, Baden-Wurttemberg, 68305, Germany

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Dresden, Saxony, 01307, Germany

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Berlin, 13353, Germany

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Essen, 45136, Germany

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Bologna, BO, 40138, Italy

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Florence, FI, 50134, Italy

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Milan, MI, 20133, Italy

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Milan, MI, 20141, Italy

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Roma, RM, 00168, Italy

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Vicenza, VI, 36100, Italy

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Naples, 80131, Italy

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Novartis Investigative Site

Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

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Kota Kinabalu, Sabah, 88996, Malaysia

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Novartis Investigative Site

Kuching, Sarawak, 93586, Malaysia

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Novartis Investigative Site

Kuala Lumpur, 59100, Malaysia

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Monterrey, Nuevo León, 64460, Mexico

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Mexico City, 04700, Mexico

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Eindhoven, 5623 EJ, Netherlands

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Loures, 2674-514, Portugal

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Porto, 4200-072, Portugal

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Arkhangelsk, 163045, Russia

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Singapore, 119074, Singapore

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Singapore, 168583, Singapore

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Bratislava, 83310, Slovakia

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Seoul, Korea, 03080, South Korea

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Novartis Investigative Site

Seoul, 03722, South Korea

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Pamplona, Navarre, 31008, Spain

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Novartis Investigative Site

Barcelona, 08035, Spain

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Novartis Investigative Site

Barcelona, 08036, Spain

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Novartis Investigative Site

Córdoba, 14004, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Valencia, 46010, Spain

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Novartis Investigative Site

Taichung, 407219, Taiwan

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Novartis Investigative Site

Taipei, 10002, Taiwan

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Novartis Investigative Site

Taipei, 11217, Taiwan

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Novartis Investigative Site

Izmir, Karsiyaka, 35575, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, Sihhiye-Altindag, 06230, Turkey (Türkiye)

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Novartis Investigative Site

Adana, Yuregir, 01230, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06520, Turkey (Türkiye)

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Novartis Investigative Site

Glasgow, G12 0YN, United Kingdom

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Novartis Investigative Site

London, SE1 9RT, United Kingdom

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Novartis Investigative Site

Manchester, M20 2BX, United Kingdom

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Related Publications (1)

• Konstantinopoulos PA, Gonzalez-Martin A, Cruz FM, Friedlander M, Glasspool R, Lorusso D, Marth C, Monk BJ, Kim JW, Hinson P, Ajipa O, Pretre V, Han Y, Matulonis UA. EPIK-O/ENGOT-OV61: alpelisib plus olaparib vs cytotoxic chemotherapy in high-grade serous ovarian cancer (phase III study). Future Oncol. 2022 Oct;18(31):3481-3492. doi: 10.2217/fon-2022-0666. Epub 2022 Sep 6.

  PMID: 36066851 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Alpelisib; olaparib; Paclitaxel; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 28, 2021
• Study Start: July 22, 2021
• Primary Completion: April 21, 2023
• Study Completion: January 19, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

IT (7); SL (1); TW (3); TU (4); AU (2); US (16); PT (2); KR (2); DK (2); FI (3); ES (6); GB (3); CA (4); DE (4); SG (2); CZ (3); RU (1); AR (3); BR (2); CN (5); BE (3); FR (5); MY (4); ME (2); NL (1)