Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Immune System Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

somatic BRCA mutant, germline BRCA wild type

genomic instability positive and no BRCA mutation

genomic instability negative and no BRCA mutation

300 mg olaparib tablets taken orally twice daily

OLAPARIB

This is a non-randomized, open-label study to assess olaparib tablets as a treatment for subjects with different homologous recombination deficiency (HRD) tumor status and with platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid ovarian cancer. Subjects should have received at least 1 prior line of platinum-based chemotherapy.

This is a Phase II, open-label, non-randomized, multi-center study assessing the efficacy and safety of olaparib tablets 300 mg (two 150 mg tablets) given orally twice daily (bid) in subjects with platinum-sensitive or partially platinum-sensitive, relapsed, high-grade serous or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received at least 1 prior line of platinum-based chemotherapy.

The study will assess the effectiveness of olaparib tablets as measured by the objective response rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, in subjects with germline BRCA mutations (gBRCAm), somatic BRCA mutations (sBRCAm), or potential aberrations in homologous recombination deficiency (HRD) as determined by myChoice® HRD, as well as in subjects without identifiable HRD. This study will utilize Myriad BRACAnalysis CDx® for germline BRCA analysis and a tumor test (myChoice® HRD) for tumor BRCA analysis and HRD status. Four cohorts will be identified based upon the genetic testing described above:

* Cohort 1: gBRCAm,
* Cohort 2: sBRCAm and germline BRCA wild type,
* Cohort 3: myChoice® HRD positive (genomic instability positive) and BRCA wild type (BRCAwt) (no BRCA mutation),
* Cohort 4: myChoice® HRD negative (genomic instability negative) and BRCAwt (no BRCA mutation).

Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status

Non-Randomized, Open-Label Phase II Study to Assess Olaparib Tablets as a Treatment for Subjects With Different HRD Tumor Status and With Platinum-Sensitive, Relapsed, High-Grade Serous or High-Grade Endometrioid Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That Have Received at Least 1 Prior Line of Chemotherapy

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using ORR according to RECIST v1.1 criteria (Investigator determined)

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using duration of response

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using CA-125 response rate

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using disease control rate (DCR). DCR is defined as the percentage of subjects with a best overall response of CR or PR (at any time up to and including the defined analysis cut-off point) or who have demonstrated stable disease (SD) for at least 8 weeks from first dose, divided by the number of subjects in the efficacy analysis set.

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using progression free survival

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using time to any progression

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using overall survival

To determine the clinical effectiveness of olaparib treatment in each of 4 cohorts assessed using HRRm gene panel status related to clinical outcome

AstraZeneca

Adverse events and serious adverse events are reported in the safety analysis set including all patients who received at least one dose of study treatment. Between the primary analysis data cut-off and final data cut-off (12-month overall survival), only serious adverse events, adverse events of special interest, and adverse events leading to discontinuation were collected.

COHORT 1

COHORT 2

COHORT 3

COHORT 4

UNASSIGNED

Unassigned

Total

A total of 272 subjects enrolled. One subject did not receive treatment and was excluded from analysis (Cohort 2 patient).

Age, Continuous

Female

Sex/Gender, Customized

WHITE

BLACK OR AFRICAN AMERICAN

ASIAN

NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER

AMERICAN INDIAN OR ALASKA NATIVE

OTHER

Race/Ethnicity, Customized

Global Clinical Lead

Cohort 1

Cohort 2

Objective Response Rate, Defined as the Percentage of Subjects With a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR)

Duration of Response, for Those Subjects With a Confirmed Response of CR or PR

CA-125 Response Rate, Defined as the Percentage of Subjects With a CA-125 Response According to GCIG Criteria Divided by the Number of Subjects Evaluable for CA-125 Response

Disease Control Rate Defined as the Percentage of Subjects Who Have a Best Overall Response of CR or PR or SD at Greater Than or Equal to 8 Weeks Divided by the Number of Subjects in the Efficacy Analysis Set, Prior to Any PD Event

Progression Free Survival

Time to Any Progression

Overall Survival

HRD positive and no BRCA mutation, HRRm positive

Cohort 3, HRRm Pos

HRD positive and no BRCA mutation, HRRm negative

Cohort 3, HRRm Neg

HRD negative and no BRCA mutation, HRRm positive

Cohort 4, HRRm Pos

HRD negative and no BRCA mutation, HRRm negative

Cohort 4, HRRm Neg

HRD Status as Per HRRm Gene Panel Assessment Will be Correlated With Clinical Outcome (ORR) for Subjects Enrolled in the 2 Cohorts With BRCAwt (Cohorts 3 and 4)

Overall Study

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Disease Susceptibility

Gemcitabine

Paclitaxel

Doxorubicin

Liposomal doxorubicin

Albumin-Bound Paclitaxel

Topotecan

Physician's choice single agent chemotherapy

300 mg olaparib tablets taken orally twice daily. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria.

Treatment of relapsed disease with single agent chemotherapy based on physician's choice of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria

Single agent chemotherapy

Richard T Penson, Associate Prof. of Medicine

Comparison of olaparib vs. physician's choice of single agent standard of care non-platinum based chemotherapy in patients with germline Breast Cancer susceptibility gene (gBRCA) mutated ovarian cancer who have progressed at least 6 months after the last platinum based chemotherapy. Patient should have received at least 2 prior lines of platinum based chemotherapy. The aim of the study is to assess the efficacy and safety of olaparib tablets.

This open label, randomised, controlled, multi-centre study will assess the efficacy and safety of single agent olaparib vs. standard of care, based on physician's choice of single agent chemotherapy ( i.e paclitaxel, or topotecan, or pegylated liposomal doxorubicin, or gemcitabine) in platinum sensitive or partially platinum sensitive relapsed ovarian cancer patients who carry germline deleterious or suspected deleterious BRCA mutation and who have received at least 2 prior lines of platinum based chemotherapy. Patients are eligible to undergo BRCA testing even if they have not yet had recurrence or progression of disease \>6 months (\>/=183 days) after completion of their last platinum therapy.

Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments

A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Olaparib Monotherapy Versus Physician's Choice Single Agent Chemotherapy in the Treatment of Platinum Sensitive Relapsed Ovarian Cancer in Patients Carrying Germline BRCA1/2 Mutations.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

To determine the efficacy of olaparib vs. physician's choice single agent chemotherapy by assessment of Objective Response Rate (ORR) using blinded independent central review (BICR)

Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used by a Blinded Independent Central Review (BICR) to assess participant response to treatment

ORR is the number of participants with Complete Response (CR) or Partial Response (PR) in the Measurable Disease Analysis Set (MDAS). Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each. Partial response is declared when there is a decrease in sum of diameters of target lesions ≥ 30%.

To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by progression free survival (PFS) using BICR assessment according to RECIST 1.1 criteria

PFS is defined as the time from randomization until the date of objective radiological disease progression according to RECIST 1.1 or death (by any cause in the absence of disease progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to disease progression (i.e., date of RECIST progression/death or censoring - date of randomization +1).

To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by second progression (PFS2).

Time from randomization to PFS2 is defined as the time from the date of randomization to the earliest of the progression events subsequent to first progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could involve objective radiological, clinical, cancer antigen-125 (CA-125) progression or death. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG) criteria.

To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by overall survival (OS).

Overall survival is defined as the time from the date of randomisation until death due to any cause.

To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time to earliest progression by RECIST 1.1 or CA-125 or death.

Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG).

To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time from randomisation to first subsequent therapy or death (TFST)

TFST is defined as the time from the date of randomisation to the earlier of first subsequent chemotherapy start date or death.

Anti-cancer treatments include chemotherapy and targeted agents.

To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time from randomisation to second subsequent therapy or death (TSST)

TSST was defined as the time from the date of randomisation to the earlier of second subsequent chemotherapy start date or death.

Anti-cancer treatments include chemotherapy and targeted agents.

To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time to study treatment discontinuation or death (TDT)

TDT was defined as the time from randomization to the earlier of the date of study treatment discontinuation or death.

To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by duration of response (DoR) by BICR using RECIST 1.1 criteria for evaluable patients.

Duration of response is the time from the first documentation of complete response (CR) or partial response (PR) until the date of progression or death, or the last evaluable RECIST assessment for participants that do not progress or progress after 2 missed assessments. Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment.

To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time to response (TTR) by BICR using RECIST 1.1 criteria for evaluable patients.

TTR was defined as the time from randomization until the date of first documented response by Blinded independent central review (BICR) assessment.

To compare the efficacy of single agent olaparib versus physician's choice single agent chemotherapy on the Health-related Quality of Life (HRQoL) as measured by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)

The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. TOI score ranges from 0 to 100, a higher score indicates a higher HRQoL. A negative change in score from baseline indicated a worsening in symptoms.

To compare the efficacy of single agent olaparib versus physician's choice single agent chemotherapy on the Health-related Quality of Life (HRQoL) as measured by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)

The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. TOI score ranges from 0 to 100, a higher score indicates a higher health-related quality of life (HRQoL). A change in at least 10 points was considered clinically relevant.

BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).

The number of participants with complete or partial response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Partial response is declared when there is a decrease in sum of target disease ≥ 30%. Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each.

BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).

Progressive disease was defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).

BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).

OS in BRCA gene population was measured by the number of participants who died due to any cause.

BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).

Anti-cancer treatments include chemotherapy and targeted agents.

Summary of plasma concentrations (ug/mL) of olaparib

An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.

Myriad Genetic Laboratories, Inc.

Merck Sharp & Dohme LLC

All-Cause Mortality was collected for the Full Analysis Set (FAS).

Serious Adverse Events and Other Adverse Events were collected for the Safety Analysis Set (SAS), which includes patients who received at least 1 dose of the randomised study treatment.

Participants received olaparib twice daily as a 300 mg tablet.

Olaparib 300 mg bd

Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.

Single Agent Chemotherapy

Olaparib 300mg BID

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black Or African American

Asian

American Indian Or Alaska Native

Other

Baseline characteristics are displayed for all participants who started the study. This includes the 12 participants who did not receive treatment in the 'Single Agent Chemotherapy' arm.

Global Clinical Leader

Olaparib 300 mg BID

The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.

Objective Response Rate (ORR)

The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.

Progression Free Survival (PFS)

Time From Randomisation to Second Progression (PFS2)

Overall Survival (OS)

Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death

Time From Randomization To First Subsequent Therapy Or Death (TFST)

Time From Randomization To Second Subsequent Therapy Or Death (TSST)

Time From Randomization To Study Treatment Discontinuation Or Death (TDT)

Duration of Response (DoR)

Time to Response (TTR)

Selected Chemotherapy

Mean Change From Baseline In Trial Outcome Index (TOI) Score

Number of Participants Who Show an Improvement in TOI Score

Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR)

Number of Participants Who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR)

Number of Participants Who Experienced Second Progression or Death (PFS2) in BRCA Gene Population

Overall Survival (OS) in BRCA Gene Population

Number of Participants Who Discontinued Study Treatment or Died in BRCA Gene Population

Number of Participants Who Received Subsequent Chemotherapy or Died in BRCA Gene Population

Number of Participants Who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population

Day 1, 1 hour post-dose

Day 29, pre-dose

The pharmacokinetic (PK) analysis set includes all participants who received an olaparib dose and provided evaluable plasma concentration data.

Geometric Mean Plasma Concentration of Olaparib

The safety analysis set includes all participants who received at least 1 dose of randomized study treatment, olaparib or chemotherapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status	NCT02983799	Relapsed Ovaria...	OLAPARIB	18 Years - 130 Years	AstraZeneca
Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments	NCT02282020	Relapsed Ovaria...	OLAPARIB Single agent ch...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for relapsed ovarian cancer, brca mutation, platinum sensitivity