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)

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT03742895
• Date of registration: 14/11/2018
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme LLC
• Public title: 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)
• Scientific title: A Phase 2 Study of Olaparib Monotherapy in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer
• Date of first enrolment: December 12, 2018
• Target sample size: 390
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03742895
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, Canada, Colombia, Denmark, France, Guatemala, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Peru, Romania, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Toll Free Number

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme LLC

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Advanced Solid Neoplasms

Intervention(s)

Drug: Olaparib

Primary Outcome(s)

Objective Response Rate (ORR) [Time Frame: Up to 53 months]

Secondary Outcome(s)

Number of Participants Experiencing an Adverse Event (AE) [Time Frame: Up to 53 months]

Progression Free Survival (PFS) [Time Frame: Up to 53 months]

Prostate-specific Antigen (PSA) Response Rate in Participants with Prostate Cancer [Time Frame: Up to 53 months]

Duration of Response (DOR) [Time Frame: Up to 53 months]

Overall Survival (OS) [Time Frame: Up to 53 months]

Time to Earliest Progression by Cancer Antigen-125 (CA-125) [Time Frame: Up to 53 months]

Objective Response Rate (ORR) in Participants with HRRm or HRD Positive Cancer [Time Frame: Up to 53 months]

Progression-Free Survival After Next-Line Treatment in Participants with sBRCAm Breast Cancer [Time Frame: Up to 53 months]

Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE) [Time Frame: Up to 52 months]

Secondary ID(s)

LYNK-002

7339-002

MK-7339-002

194694

2018-003007-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

AstraZeneca