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CLINICAL STUDY · NCT04729387

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

TerminatedPhase 3Interventional

Sponsored by Novartis Pharmaceuticals

Condition
Ovarian Cancer
Study locations
93 reported sites
Study updated
19 Oct 2026
Source
ClinicalTrials.gov

Overall study status is shown above. Individual hospitals may have a different recruitment status.

THE STUDY

About this study

The objective of this study was to evaluate the efficacy and safety of alpelisib in combination with olaparib compared with single-agent cytotoxic chemotherapy in participants with platinum-resistant or platinum-refractory, germline BRCA non-mutated (gBRCAnm) high-grade serous ovarian cancer (HGSOC), with progression-free survival (PFS) as the primary efficacy endpoint.
Full official title
EPIK-O: A Phase III, Multi-center, Randomized (1:1), Open-label, Active-controlled, Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Olaparib as Compared to Single Agent Cytotoxic Chemotherapy, in Participants With no Germline BRCA Mutation Detected, Platinum-resistant or Refractory, High-grade Serous Ovarian Cancer
Detailed description
This study enrolled adult women with platinum-resistant or platinum-refractory high-grade serous ovarian cancer (HGSOC) who did not have a detected germline BRCA mutation. In this open-label, active-controlled study, participants were randomized 1:1 to receive either alpelisib plus olaparib or single-agent cytotoxic chemotherapy (paclitaxel or pegylated liposomal doxorubicin \[PLD\]).

The study comprised four phases: a 28-day pre-treatment phase, a randomized treatment phase, a post-treatment follow-up phase for safety and efficacy assessments, and a post-treatment survival follow-up phase. Participants continued study treatment until disease progression, unacceptable toxicity, death, or discontinuation for any other reason.

Because the study did not achieve its primary objective, Protocol Amendment 03 removed the post-treatment survival follow-up phase. Subsequently, Protocol Amendment 04 modified the study design by removing the efficacy follow-up phase.
Reason the study stopped
Sponsor Decision

PARTICIPATION

Who may participate

Minimum age
18 Years
Maximum age
100 Years
Sex eligibility
All sexes
Healthy volunteers
Not accepted

Only the study team can confirm eligibility. The registry criteria below are not a medical recommendation.

Full inclusion and exclusion criteria
Key Inclusion criteria:

* Participant had 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 Response Evaluation Criteria in Solid Tumors (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 was present, the disease was assessable by Gynecologic Cancer Intergroup criteria (GCIC) for CA-125.
* Participant had no germline BRCA1/2 mutation as determined by an FDA-approved assay.
* Participant had an ECOG performance status of 0 or 1.
* Participant had 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 was not an option, according to the Gynecologic Cancer Intergroup criteria (GCIG) 5th Ovarian Cancer Consensus Conference definitions.
* Participant must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy was appropriate as the next line of treatment.
* Participant had received prior bevacizumab or was not eligible to receive bevacizumab due to medical reasons.

Key Exclusion criteria:

* Participant had received prior treatment with any phosphoinositide 3-kinase, mammalian Target Of Rapamycin or Protein Kinase B inhibitor.
* Participant was concurrently using other anti-cancer therapy.
* Participant was in a state of small or large bowel obstruction or had other impairment of gastrointestinal (GI) function or GI disease.
* Participant had surgery within 14 days prior to starting study drug or had not recovered from major adverse effects.
* Participant had not recovered from all toxicities related to prior anticancer therapies to baseline or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Grade ≤1. Exception to this criterion: participants with any grade of alopecia were allowed to enter the study.
* Participant had 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 had received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to randomization, and who had not recovered to baseline, grade 1 or better from related adverse effects of such therapy (with the exception of alopecia).
* Participant had known hypersensitivity to any of the study drugs or excipients.
* Participant had a history of myelodysplastic syndrome or acute myeloid leukemia, or presented clinical and/ or laboratory features suggestive thereof.

Other inclusion/exclusion criteria may apply

Additional eligibility information

Adult women

NEAR YOU

Study locations worldwide

93 sites

Check the individual site’s status and contact the listed study team for current availability.

Arizona Oncology Associates

Not reported

Phoenix, Arizona, 85016, United States

Contact details are not published in this record. Check official study record ↗

Florida Cancer Specialists

Not reported

Fort Myers, Florida, 33901, United States

Contact details are not published in this record. Check official study record ↗

Florida Cancer Specialists

Not reported

West Palm Beach, Florida, 33401, United States

Contact details are not published in this record. Check official study record ↗

Maryland Oncology Hematology P A

Not reported

Silver Spring, Maryland, 20904, United States

Contact details are not published in this record. Check official study record ↗

Massachusetts General Hospital

Not reported

Boston, Massachusetts, 02114, United States

Contact details are not published in this record. Check official study record ↗

Dana Farber Cancer Institute

Not reported

Boston, Massachusetts, 02115, United States

Contact details are not published in this record. Check official study record ↗

Memorial Sloan Kettering Cancer Ctr

Not reported

New York, New York, 10065, United States

Contact details are not published in this record. Check official study record ↗

Oncology Hematology Care Inc

Not reported

Cincinnati, Ohio, 45242, United States

Contact details are not published in this record. Check official study record ↗

University Of Cincinnati

Not reported

Cincinnati, Ohio, 45267, United States

Contact details are not published in this record. Check official study record ↗

Avera Cancer Institute

Not reported

Sioux Falls, South Dakota, 57106, United States

Contact details are not published in this record. Check official study record ↗

Texas Oncology Northeast Texas

Not reported

Tyler, Texas, 75702, United States

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

CABA, Buenos Aires, C1125ABD, Argentina

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Bedford Park, South Australia, 5041, Australia

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Shepparton, Victoria, 3630, Australia

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

São Paulo, São Paulo, 04014-002, Brazil

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Vancouver, British Columbia, V5Z 4E6, Canada

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Mannheim, Baden-Wurttemberg, 68305, Germany

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Kota Kinabalu, Sabah, 88996, Malaysia

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Monterrey, Nuevo León, 64460, Mexico

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Izmir, Karsiyaka, 35575, Turkey (Türkiye)

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

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

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Adana, Yuregir, 01230, Turkey (Türkiye)

Contact details are not published in this record. Check official study record ↗

Novartis Investigative Site

Not reported

Manchester, M20 2BX, United Kingdom

Contact details are not published in this record. Check official study record ↗

WHAT IS BEING STUDIED

Treatments and study groups

Interventions

AlpelisibDrug
Alpelisib was 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

Study groups: Alpelisib+olaparib

Other names: BYL719

OlaparibDrug
Olaparib was 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.

Study groups: Alpelisib+olaparib

PaclitaxelDrug
Paclitaxel (80 mg/m²) was administered as a weekly intravenous infusion on Days 1, 8, 15, and 22 of each 28-day cycle.

Study groups: Paclitaxel or Pegylated liposomal doxorubicin

Pegylated liposomal doxorubicin (PLD)Drug
Pegylated liposomal doxorubicin (40-50 mg/m² at physician discretion) was administered as an intravenous infusion once every 28 days starting on Cycle 1 Day 1.

Study groups: Paclitaxel or Pegylated liposomal doxorubicin

Study groups

Alpelisib+olaparibExperimental
Alpelisib (200 mg once daily after food) and Olaparib (200 mg twice daily) were both administered orally on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle.

Interventions: Drug: Alpelisib, Drug: Olaparib

Paclitaxel or Pegylated liposomal doxorubicinActive comparator
Paclitaxel (80 mg/m²) was administered as a weekly intravenous infusion on Days 1, 8, 15, and 22 of each 28-day cycle, or Pegylated liposomal doxorubicin (40-50 mg/m² at physician discretion) was administered as an intravenous infusion once every 28 days starting on Cycle 1 Day 1.

Interventions: Drug: Paclitaxel, Drug: Pegylated liposomal doxorubicin (PLD)

RESEARCH DETAILS

Study design

Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Study model
Parallel
Masking
None (open label)
Enrolment
358 participants · Actual

TIMELINE & MEASURES

Dates and outcomes

Study started
22 Jul 2021 · Actual
Primary completion
21 Apr 2023 · Actual
Study completion
19 Jan 2026 · Actual
First registered
28 Jan 2021 · Actual
Last registry update
19 Oct 2026 · Actual
Status last verified
Sep 2026
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 to the first documented disease progression or death from any cause, as determined by blinded independent review committee (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.

Disease progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including baseline), with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of non-target lesions.

Time frame: From randomization until the date of the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 months

Secondary outcomes (15)

Overall Survival

Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If a participant was not known to have died, OS was censored at the latest date the participant was known to be alive (on or before the cut-off date), i.e., the last known date the participant was alive (last contact date).

Time frame: 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

Overall Response Rate (ORR) was defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) by blinded independent review committee (BIRC) assessment as per RECIST 1.1 criteria:

* CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
* PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Time frame: Up to approximately 21 months

Clinical Benefit Rate (CBR) With Confirmed Response Based on BIRC Assessment According to RECIST 1.1

Clinical benefit rate (CBR) with confirmed response was defined as the percentage of participants whose best overall response was a confirmed CR or PR, or stable disease (SD) maintained for at least 24 weeks. CR, PR, and SD were determined by BIRC according to RECIST 1.1 criteria.

Time frame: Up to approximately 21 months

Time to Response (TTR) Based on BIRC Assessment and According to RECIST 1.1

Time to response (TTR) was defined as the interval from randomization to the first documented occurrence of either complete response (CR) or partial response (PR), which was subsequently confirmed (using the date of initial response, not the confirmation date). CR and PR were determined based on tumor response data assessed by BIRC according to RECIST 1.1 criteria.

Time frame: 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

Duration of response (DOR) with confirmed response was calculated only for participants whose best overall response was a confirmed complete response (CR) or confirmed partial response (PR), based on tumor response data assessed by BIRC according to RECIST 1.1. The start date was the date of the first documented CR or PR (i.e., the initial response date, not the confirmation date), and the end date was the date of first documented disease progression or death due to underlying cancer. Participants without progression or cancer-related death were censored at the date of their last adequate tumor assessment.

Time frame: From first documented response to first documented progression or death, assessed up to approximately 21 months

Time to Definitive Deterioration of the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Performance status (PS) was evaluated using the ECOG scale, which comprises six grades (0 to 5), where 0 represents fully active and 5 represents death. Time to definitive deterioration in ECOG PS was defined as the interval from randomization to the date when ECOG PS worsened by at least one category from baseline and remained worsened. Deterioration was considered definitive if there was no subsequent improvement to the baseline category or better. Participants were censored if no definitive deterioration occurred before the earlier of: (i) the analysis cut-off date or (ii) initiation of a new anti-neoplastic therapy. The censoring date was the date of the last PS assessment prior to the cut-off or start of new therapy.

Time frame: Up to approximately 18 months

Number of Participants With Dose Interruptions and Dose Reductions

The number of participants with dose reductions/interruptions was assessed and summarized by study treatment.

Time frame: From randomization until end of treatment, assessed up to approximately 39 months with alpelisib or olaparib, 45 months with paclitaxel, and 23 months with pegylated liposomal doxorubicin (PLD)

Dose Intensity for Alpelisib and Olaparib

Dose intensity was computed as the ratio of actual cumulative dose received to actual duration of exposure and summarized by study treatment.

Time frame: From randomization until end of treatment, assessed up to approximately 39 months

Dose Intensity for Paclitaxel

Dose intensity was computed as the ratio of actual cumulative dose received to actual duration of exposure and summarized by study treatment.

Time frame: From randomization until end of treatment, assessed up to approximately 45 months

Dose Intensity for Pegylated Liposomal Doxorubicin

Dose intensity was computed as the ratio of actual cumulative dose received to actual duration of exposure and summarized by study treatment.

Time frame: From randomization until end of treatment, assessed up to approximately 23 months

Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of Alpelisib and Olaparib

Venous whole blood samples were collected to characterize the pharmacokinetics of alpelisib when administered in combination with olaparib. AUCtau was listed and summarized using descriptive statistics.

Time frame: Cycle 1 Day 8 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose)

Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Alpelisib and Olaparib

Venous whole blood samples were collected to characterize the pharmacokinetics of alpelisib when administered in combination with olaparib. AUClast was listed and summarized using descriptive statistics.

Time frame: Cycle 1 Day 8 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose)

Maximum Concentration (Cmax) of Alpelisib and Olaparib

Venous whole blood samples were collected to characterize the pharmacokinetics of alpelisib when administered in combination with olaparib. Cmax was listed and summarized using descriptive statistics.

Time frame: Cycle 1 Day 8 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose)

Time to Reach Maximum Concentration (Tmax) of Alpelisib and Olaparib

Venous blood samples were collected to characterize the pharmacokinetics (PK) of alpelisib when administered in combination with olaparib. Time to maximum observed plasma concentration (Tmax) was calculated using actual sample collection times rather than nominal scheduled sampling times and was summarized using descriptive statistics.

Time frame: Cycle 1 Day 8 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose)

Time to Definitive Deterioration by 10% in FACT-O Trial Outcomes Index (TOI) Score

The Functional Assessment of Cancer Therapy-Ovarian (FACT O) is a validated instrument that evaluates quality of life in patients with ovarian cancer. The Trial Outcome Index (TOI) of the FACT-O combines Physical Well Being (PWB), Functional Well Being (FWB), and the Ovarian Cancer Subscale (OCS), and its scores range from 0 to 100, with higher scores indicating better quality of life and physical/functional status. Time to definitive deterioration by 10% in FACT O TOI is defined as the time from randomization to the first occurrence of at least a 10% worsening from baseline with no subsequent improvement above this threshold, or death. Participants without an event before analysis cut off or before starting another anticancer therapy were censored at their last adequate assessment. Time to deterioration was estimated using the Kaplan-Meier method.

Time frame: Baseline, up to 15 months

STUDY TEAM

Sponsor and contacts

Lead sponsor
Novartis Pharmaceuticals
Sponsor type
Industry
Collaborators
Not reported
Organisation study ID
CBYL719K12301

Central study contacts

No central contact is currently reported. Check the site contacts or the official record.

Study officials
Novartis PharmaceuticalsStudy director · Novartis Pharmaceuticals

Contacts are provided by the registry for study enquiries. Do not use these details for marketing or promotions.

FURTHER READING

Results, documents and references

Results are available on the registry

Published results can include participant flow, outcome measurements and adverse events. Review the full tables and their context on ClinicalTrials.gov.

Read the full study results ↗

Available documents

  • Study Protocol — 5 Dec 2024
  • Statistical Analysis Plan — 20 Jun 2023

Open and download documents on the official record ↗

Publications (2)
  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. PubMed ↗
  2. Konstantinopoulos PA, Kim JW, Freyer G, Lee JY, Gaba L, Grisham RN, Colombo N, Wu X, Sehouli J, Cruz F, Cibula D, Monk BJ, Nyvang GB, Friedlander M, Lorusso D, Van Nieuwenhuysen E, Malik R, Glasspool R, Marth C, Leary A, Cortes-Salgado A, Zamagni C, Marme F, Sufliarsky J, Hinson P, Zuradelli M, Wang C, Su F, Paule I, Miller M, Matulonis UA, Gonzalez-Martin A. Primary Analysis of EPIK-O/ENGOT-ov61: Alpelisib Plus Olaparib Versus Chemotherapy in Platinum-Resistant or Platinum-Refractory High-Grade Serous Ovarian Cancer Without BRCA Mutation. J Clin Oncol. 2025 Sep 10;43(26):2908-2917. doi: 10.1200/JCO-25-00225. Epub 2025 Jul 23. PubMed ↗

Source: ClinicalTrials.gov · Data fetched 20 Oct 2026, 15:51 GMT+0530

Registry data timestamp: 2026-10-19T09:00:04

Registry content is reformatted for readability; original study text is not rewritten. Missing information is labelled “Not reported”. Records are supplied by study sponsors or investigators and can change.

ClinicalTrials.gov does not endorse PharmaBharat. Listing a study does not mean it has been evaluated or approved by a government agency. Information is for research awareness and is not medical advice. Data source terms · Registry disclaimer

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