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JOURNAL ONKOLOGIE – STUDIE

Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)

Rekrutierend

NCT-Nummer:
NCT03742895

Studienbeginn:
Dezember 2018

Letztes Update:
05.04.2024

Wirkstoff:
Olaparib

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
AstraZeneca

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 130)

The University of Arizona Cancer Center - North Campus ( Site 0011)
85721 Tucson
United StatesAbgeschlossen» Google-Maps
St Joseph Heritage Healthcare-Oncology ( Site 0056)
92835 Fullerton
United StatesAbgeschlossen» Google-Maps
Cedars Sinai Medical Center ( Site 0002)
90048 Los Angeles
United StatesAbgeschlossen» Google-Maps
UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0007)
94158 San Francisco
United StatesAbgeschlossen» Google-Maps
Rocky Mountain Regional Veterans Affairs Medical Center ( Site 0092)
80045 Aurora
United StatesAbgeschlossen» Google-Maps
Winship Cancer Institute of Emory University ( Site 0025)
30322-1013 Atlanta
United StatesAbgeschlossen» Google-Maps
Augusta University ( Site 0028)
30912 Augusta
United StatesAbgeschlossen» Google-Maps
Markey Cancer Center ( Site 0018)
40536 Lexington
United StatesAbgeschlossen» Google-Maps
Weinberg Cancer Institute at Franklin Square ( Site 0054)
21237 Baltimore
United StatesAbgeschlossen» Google-Maps
University of Massachusetts ( Site 0017)
01655 Worcester
United StatesAbgeschlossen» Google-Maps
Henry Ford Health System ( Site 0060)
48202 Detroit
United StatesAbgeschlossen» Google-Maps
Cancer Partners of Nebraska ( Site 0051)
68510 Lincoln
United StatesAbgeschlossen» Google-Maps
VA New York Harbor Healthcare System Manhattan ( Site 0094)
10010 New York
United StatesAbgeschlossen» Google-Maps
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0057)
10016 New York
United StatesAbgeschlossen» Google-Maps
Southwestern Regional Medical Center, Inc. ( Site 0079)
74133 Tulsa
United StatesAbgeschlossen» Google-Maps
Eastern Regional Medical Center, Inc. ( Site 0077)
19124 Philadelphia
United StatesAbgeschlossen» Google-Maps
Sanford Hematology Oncology-Sioux Falls SD ( Site 0012)
57104 Sioux Falls
United StatesAbgeschlossen» Google-Maps
Intermountain Healthcare ( Site 0043)
84790 Saint George
United StatesAbgeschlossen» Google-Maps
Virginia Mason Medical Center ( Site 0052)
98101 Seattle
United StatesAbgeschlossen» Google-Maps
Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 2703)
B1884BBF Berazategui
ArgentinaAbgeschlossen» Google-Maps
Hospital Britanico de Buenos Aires ( Site 2704)
C1280AEB Ciudad de Buenos Aires
ArgentinaAbgeschlossen» Google-Maps
Instituto de Investigaciones Metabolicas ( Site 2700)
C1012AAR Buenos Aires
ArgentinaAbgeschlossen» Google-Maps
MNCCI Port Macquarie Base Hospital ( Site 2201)
2444 Port Macquarie
AustraliaAbgeschlossen» Google-Maps
Linear Clinical Research Ltd ( Site 2202)
6009 Nedlands
AustraliaAbgeschlossen» Google-Maps
Jewish General Hospital ( Site 0209)
H3T 1E2 Montreal
CanadaAbgeschlossen» Google-Maps
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
G1J 1Z4 Quebec
CanadaAbgeschlossen» Google-Maps
Fundacion Centro de Investigacion Clinica CIC ( Site 2812)
050021 Medellin
ColombiaAbgeschlossen» Google-Maps
Rodrigo Botero SAS ( Site 2801)
050030 Medellin
ColombiaAbgeschlossen» Google-Maps
Biomelab S A S ( Site 2800)
080001 Barranquilla
ColombiaAbgeschlossen» Google-Maps
Oncomedica S.A. ( Site 2806)
230002 Monteria
ColombiaAbgeschlossen» Google-Maps
Administradora Country SA - Clinica del Country ( Site 2802)
110221 Bogota
ColombiaAbgeschlossen» Google-Maps
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 2807)
110311 Bogota
ColombiaAbgeschlossen» Google-Maps
Instituto Nacional de Cancerologia E.S.E ( Site 2809)
111511 Bogota
ColombiaAbgeschlossen» Google-Maps
C. Medico Imbanaco Cali S.A. ( Site 2810)
760042 Cali
ColombiaAbgeschlossen» Google-Maps
Rigshospitalet ( Site 0402)
2100 Copenhagen
DenmarkAbgeschlossen» Google-Maps
Odense Universitetshospital ( Site 0400)
5000 Odense
DenmarkAbgeschlossen» Google-Maps
Centre Antoine Lacassagne ( Site 0610)
06189 Nice
FranceAbgeschlossen» Google-Maps
Centre Georges Francois Leclerc ( Site 0608)
21000 Dijon
FranceAbgeschlossen» Google-Maps
Institut Bergonie ( Site 0603)
33076 Bordeaux
FranceAbgeschlossen» Google-Maps
Mater Misericordiae University Hospital ( Site 1654)
D07 WKW8 Dublin
IrelandAbgeschlossen» Google-Maps
Bon Secours Hospital ( Site 1656)
T12 DV56 Cork
IrelandAbgeschlossen» Google-Maps
Tallaght University Hospital ( Site 1652)
D24 NROA Dublin
IrelandAbgeschlossen» Google-Maps
Soroka Medical Center ( Site 0800)
8457108 Beer-Sheva
IsraelAbgeschlossen» Google-Maps
Rambam Health Care Campus-Oncology Division ( Site 0801)
3109601 Haifa
IsraelAbgeschlossen» Google-Maps
Hadassah Ein Kerem Medical Center ( Site 0802)
9112001 Jerusalem
IsraelAktiv, nicht rekrutierend» Google-Maps
Sourasky Medical Center ( Site 0804)
6423906 Tel Aviv
IsraelAbgeschlossen» Google-Maps
Istituto Nazionale Tumori Fondazione Pascale ( Site 0700)
80131 Napoli
ItalyAbgeschlossen» Google-Maps
Istituto Clinico Humanitas Research Hospital ( Site 0703)
20089 Rozzano
ItalyAbgeschlossen» Google-Maps
Policlinico Le Scotte di Siena ( Site 0704)
53100 Siena
ItalyAbgeschlossen» Google-Maps
Aichi Cancer Center Hospital ( Site 2602)
464-8681 Nagoya
JapanAktiv, nicht rekrutierend» Google-Maps
National Cancer Center Hospital East ( Site 2600)
2778577 Kashiwa
JapanAktiv, nicht rekrutierend» Google-Maps
Kyoto University Hospital ( Site 2603)
606-8507 Kyoto-shi
JapanAbgeschlossen» Google-Maps
Osaka University Hospital ( Site 2604)
565-0871 Suita
JapanAbgeschlossen» Google-Maps
National Cancer Center Hospital ( Site 2601)
104-0045 Tokyo
JapanAktiv, nicht rekrutierend» Google-Maps
The Cancer Institute Hospital of JFCR ( Site 2605)
135-8550 Tokyo
JapanAktiv, nicht rekrutierend» Google-Maps
Severance Hospital Yonsei University Health System ( Site 2400)
03722 Seoul
Korea, Republic ofAbgeschlossen» Google-Maps
Unidad Biomedica Avanzada Monterrey S. A. ( Site 2902)
64460 Monterrey
MexicoAbgeschlossen» Google-Maps
Cuidados Oncologicos ( Site 2908)
76000 Santiago De Quetaro
MexicoAbgeschlossen» Google-Maps
Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 2901)
89440 Madero
MexicoAbgeschlossen» Google-Maps
Centro Estatal de Cancerologia de Chihuahua ( Site 2907)
31000 Chihuahua
MexicoAbgeschlossen» Google-Maps
Oaxaca Site Management Organization S.C. ( Site 2905)
68000 Oaxaca
MexicoAbgeschlossen» Google-Maps
Instituto Nacional de Enfermedades Neoplasicas ( Site 3106)
15038 Lima
PeruAbgeschlossen» Google-Maps
Hospital Nacional Guillermo Almenara Irigoyen ( Site 3107)
15033 Lima
PeruAbgeschlossen» Google-Maps
Hospital Central de la Fuerza Aerea del Peru ( Site 3104)
15046 Lima
PeruAbgeschlossen» Google-Maps
Hospital Arzobispo Loayza ( Site 3103)
15082 Lima
PeruAbgeschlossen» Google-Maps
S.C. Pelican Impex S.R.L Spitalul Clinic Pelican Oradea ( Site 1102)
410469 Oradea
RomaniaAbgeschlossen» Google-Maps
Medisprof ( Site 1107)
400641 Cluj Napoca
RomaniaAbgeschlossen» Google-Maps
SC Radiotherapy Center Cluj SRL ( Site 1105)
407280 Comuna Floresti
RomaniaAbgeschlossen» Google-Maps
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1103)
200542 Craiova
RomaniaAbgeschlossen» Google-Maps
Spitalul PDR Medlife ( Site 1106)
500152 Brasov
RomaniaAbgeschlossen» Google-Maps
S.C.Focus Lab Plus S.R.L ( Site 1101)
022548 Bucuresti
RomaniaAbgeschlossen» Google-Maps
S.C.Gral Medical S.R.L ( Site 1104)
031422 Bucuresti
RomaniaAbgeschlossen» Google-Maps
Arkhangelsk Clinical Oncological Dispensary ( Site 1204)
163045 Arkhangelsk
Russian FederationAbgeschlossen» Google-Maps
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1212)
454087 Chelyabinsk
Russian FederationSchwebend» Google-Maps
MEDSI Clinical Hospital on Pyatnitsky Highway-Departmentof Antitumor Drug therapy ( Site 1216)
143442 Krasnogorsk
Russian FederationAbgeschlossen» Google-Maps
N.N. Blokhin NMRCO ( Site 1201)
115477 Moscow
Russian FederationAbgeschlossen» Google-Maps
MSROI named after P.A. Hertsen branch of FSBI NMRC Radiology ( Site 1213)
125284 Moscow
Russian FederationSchwebend» Google-Maps
Ryazan Regional Clinical Oncology dispensary ( Site 1202)
390011 Ryazan
Russian FederationAbgeschlossen» Google-Maps
SBHI Samara Regional Clinical Oncology Dispensary ( Site 1211)
443031 Samara
Russian FederationAbgeschlossen» Google-Maps
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1208)
197758 Saint Petersburg
Russian FederationAbgeschlossen» Google-Maps
Clinical Hospital Saint Luka ( Site 1205)
194044 Saint-Petersburg
Russian FederationAbgeschlossen» Google-Maps
SBHI Leningrad Regional Clinical Hospital ( Site 1206)
194291 St.Petersburg
Russian FederationAbgeschlossen» Google-Maps
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1207)
420029 Kazan
Russian FederationSchwebend» Google-Maps
Universitaetsspital Zuerich ( Site 1400)
8091 Zuerich
SwitzerlandAbgeschlossen» Google-Maps
Hopitaux Universitaires de Geneve HUG. ( Site 1406)
1211 Geneva
SwitzerlandAbgeschlossen» Google-Maps
Hacettepe Universitesi Tıp Fakultesi ( Site 1503)
06100 Ankara
TurkeyAbgeschlossen» Google-Maps
Churchill Hospital ( Site 1606)
OX3 7LE Oxford
United KingdomAbgeschlossen» Google-Maps
Christie NHS Foundation Trust ( Site 1601)
M20 4BX Manchester
United KingdomAbgeschlossen» Google-Maps
Weston Park Hospital ( Site 1607)
S10 2SJ Sheffield
United KingdomAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This study will evaluate the efficacy and safety of olaparib (MK-7339) monotherapy in

participants with multiple types of advanced cancer (unresectable and/or metastatic) that: 1)

have progressed or been intolerant to standard of care therapy; and 2) are positive for

homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- For all participants:

- Has measurable disease per RECIST 1.1 or PCWG-modified RECIST 1.1 as assessed by the

local site Investigator/radiology and confirmed by BICR.

- Is able to provide a newly obtained core or excisional biopsy of a tumor lesion or

either an archival formalin-fixed paraffin embedded (FFPE) tumor tissue block or

slides.

- Has a life expectancy of at least 3 months.

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1,

as assessed within 7 days of treatment initiation.

- Male participants must agree to use contraception during the treatment period and for

at least 95 days (3 months and 5 days) after the last dose of study treatment and

refrain from donating sperm during this period.

- A female participant is eligible to participate if she is not pregnant or

breastfeeding, and at least one of the following conditions applies:

1. Is not a woman of childbearing potential (WOCBP).

2. Is a WOCBP and using a contraceptive method that is highly effective with low

user dependency, or be abstinent from heterosexual intercourse as their preferred

and usual lifestyle (abstinent on a long term and persistent basis), during the

intervention period and for at least 180 days after the last dose of study

intervention, AND agrees not to donate eggs (ova, oocytes) to others or

freeze/store for her own use for the purpose of reproduction during this period.

Abstains from breastfeeding during the study intervention period and for at least

30 days after the last dose of study intervention.

- Has adequate organ function.

- For participants who have non-breast or -ovarian cancers that are breast cancer

susceptibility gene 1/2 (BRCA1/2) mutated (BRCAm), or who have cancers that are

BRCA1/2 non-mutated and homologous recombination repair nonmutated:

- Has a histologically- or cytologically-confirmed advanced (metastatic and/or

unresectable) solid tumor (except ovarian cancer whose tumor has a germline or somatic

BRCA mutation and breast cancer whose tumor has a germline BRCA mutation) that is not

eligible for curative treatment and for which standard of care therapy has failed.

Participants must have progressed on or be intolerant to standard of care therapies

that are known to provide clinical benefit. There is no limit on the number of prior

treatment regimens.

- Has either centrally-confirmed known or suspected deleterious mutations in at least 1

of the genes involved in HRR or centrally-confirmed HRD.

- For participants receiving prior platinum (cisplatin, carboplatin, or oxaliplatin

either as monotherapy or in combination) for advanced (metastatic and/or unresectable)

solid tumor, have no evidence of disease progression during the platinum chemotherapy

or ≤4 weeks of completing the platinum-containing regimen.

- For participants who have somatic BRCAm breast cancer:

- Has histologically- or cytologically-confirmed breast cancer with evidence of

metastatic disease.

- Has a known or suspected deleterious mutation in breast cancer susceptibility gene

(BRCA) 1 or BRCA2 and does not harbor a germline BRCA1 or BRCA2 mutation - testing can

be done centrally or locally. Blood and tissue samples must be provided by all

participants.

- Has received treatment with an anthracycline unless contraindicated and a taxane in

either the neoadjuvant/adjuvant or metastatic setting.

- Participants with estrogen and/or progesterone receptor-positive disease must have

received and progressed on at least one endocrine therapy (adjuvant or metastatic), or

have disease that the treating physician believes to be inappropriate for endocrine

therapy.

Exclusion Criteria:

- Has a known additional malignancy that is progressing or has required active treatment

in the last 5 years. Note: Participants with basal cell carcinoma of the skin,

squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma

in situ that has undergone potentially curative therapy are not excluded.

- Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features

suggestive of MDS/AML.

- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.

Note: Participants with previously treated brain metastases may participate if

radiologically stable, clinically stable, and without requirement for steroid

treatment for at least 14 days prior to the first dose of study treatment.

- Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor

[G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant

erythropoietin) within 28 days prior to the first dose of study treatment.

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has known active hepatitis infection (i.e., Hepatitis B or C).

- Is unable to swallow orally administered medication or has a gastrointestinal disorder

affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).

- Has received prior therapy with olaparib or with any other polyadenosine 5'

diphosphoribose (poly[ADP ribose]) polymerization (PARP) inhibitor.

- Has a known hypersensitivity to the components or excipients in olaparib.

- Has received previous allogenic bone-marrow transplant or double umbilical cord

transplantation (dUCBT).

- Has received a whole blood transfusion in the last 120 days prior to entry to the

study. Packed red blood cells and platelet transfusions are acceptable if not

performed within 28 days of the first dose of study treatment.

- Has received any anti-neoplastic systemic chemotherapy or biological therapy, targeted

therapy, or an anticancer hormonal therapy within 3 weeks prior to the first dose of

study intervention.

- Has a primary cancer of unknown origin.

- Has received prior radiotherapy within 2 weeks of start of study intervention.

Participants must have recovered from all radiation-related toxicities, not require

corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted

for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

Studien-Rationale

Primary outcome:

1. Objective Response Rate (ORR) (Time Frame - Up to 53 months):
ORR is defined as the percentage of participants who achieve a confirmed complete response ([CR]; disappearance of all target lesions) or partial response ([PR]: ≥30% decrease in the sum of diameters of target lesions) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors 1.1, modified to follow a maximum of 10 target lesions in total and a maximum of 5 target lesions per organ (modified RECIST 1.1). For participants with prostate cancer, ORR will be based on Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 as assessed by BICR.



Secondary outcome:

1. Duration of Response (DOR) (Time Frame - Up to 53 months):
DOR is defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death due to any cause, whichever occurs first. DOR will be assessed by BICR according to either modified RECIST 1.1 or PCWG-modified RECIST 1.1 for participants with prostate cancer.

2. Overall Survival (OS) (Time Frame - Up to 53 months):
OS is defined as the time from the date of the first dose to the date of death due to any cause.

3. Progression Free Survival (PFS) (Time Frame - Up to 53 months):
PFS is defined as the time from the date of the first dose to either: 1) the first documented disease progression as assessed either by BICR according to modified RECIST 1.1 or PCWG-modified RECIST 1.1 for participants with prostate cancer; or 2) death due to any cause, whichever occurs first.

4. Number of Participants Experiencing an Adverse Event (AE) (Time Frame - Up to 53 months):
An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing an AE will be assessed.

5. Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE) (Time Frame - Up to 52 months):
The number of participants discontinuing study treatment due to an AE will be assessed.

6. Objective Response Rate (ORR) in Participants with HRRm or HRD Positive Cancer (Time Frame - Up to 53 months):
For participants with homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD) positive cancer, the ORR will be assessed. ORR is defined as the percentage of participants who achieve a confirmed complete response ([CR]; disappearance of all target lesions) or partial response ([PR]: ≥30% decrease in the sum of diameters of target lesions) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors 1.1, modified to follow a maximum of 10 target lesions in total and a maximum of 5 target lesions per organ (modified RECIST 1.1). For participants with prostate cancer, ORR will be based on Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 as assessed by BICR.

7. Time to Earliest Progression by Cancer Antigen-125 (CA-125) (Time Frame - Up to 53 months):
For participants with BRCA1/2 non-mutated ovarian cancer only, the time to earliest progression by CA-125 will be assessed. Progression by CA-125 is defined as an increase in CA-125 level ≥2x upper limit normal (ULN) on 2 occasions, 1 week apart. For participants with elevated CA-125 (≥ULN) at baseline, progression by CA-125 is defined as an increase in CA-125 level ≥2x the nadir value on 2 occasions, 1 week apart.

8. Prostate-specific Antigen (PSA) Response Rate in Participants with Prostate Cancer (Time Frame - Up to 53 months):
For participants with prostate cancer, the PSA response rate will be presented. PSA response rate is defined as the percentage of participants in the analysis population with PSA reduction of ≥50% from baseline measured twice at least 3 weeks apart.

9. Progression-Free Survival After Next-Line Treatment in Participants with sBRCAm Breast Cancer (Time Frame - Up to 53 months):
For participants with somatic BRCA mutated (sBRCAm) breast cancer, the PFS after next-line treatment will be presented. PFS is defined as the time from the date of the first dose to either: 1) the first documented disease progression on the next-line of treatment, as assessed by BICR according to modified RECIST 1.1; or 2) death due to any cause, whichever occurs first.

Geprüfte Regime

  • Olaparib (MK-7339 / AZD2281 / KU-0059436 / LYNPARZA® / ):
    Olaparib 300 mg administered BID as two, 150 mg oral tablets.

Quelle: ClinicalTrials.gov


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