Olaparib Plus Pembrolizumab as Post-Induction Therapy in Triple Negative Breast Cancer
- Conditions
- ocally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (TNBC)MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001892-35-IE
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 460
Type of Participant and Disease Characteristics
1. Have locally recurrent inoperable centrally confirmed TNBC that has not previously been treated with chemotherapy in the metastatic setting and that cannot be treated with curative intent OR Have metastatic TNBC that has not been previously treated with chemotherapy
2. Have been treated with anthracycline and/or a taxane in the neoadjuvant/adjuvant setting, if they received systemic treatment in the neoadjuvant/adjuvant setting, unless anthracycline and/or taxane was contraindicated or not considered the best treatment option for the participant in the opinion of the treating physician
3. Have measurable disease based on RECIST 1.1, as determined by local radiology review
4. Have provided a recently obtained or archival (no more than 3 years old) core or excisional biopsy of a tumor lesion not previously irradiated for central determination of TNBC, PD-L1, BRCA, and HRD status
5. Be a male or female at least 18 years of age on the day of signing the informed consent
6. Have an ECOG performance status of 0 or 1 as assessed within 7 days prior to the start of induction study treatment
7. Have a life expectancy =27 weeks from the day of first study treatment
8. Demonstrate adequate organ function
9. Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows:
-Olaparib: 95 days
-Pembrolizumab: no contraception requirement
-Chemotherapy: 95 days
• Refrain from donating sperm
PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR
• Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
10. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), 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 the time needed to eliminate each study intervention 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. The length of time required to continue contraception for each study intervention is as follows:
-Olaparib: 180 days
-Pembrolizumab: 120 days
-Chemotherapy: 180 days
The investigator should evaluate the potential for contraceptive method failure (ie,noncompliance, recently initiated) in relationship to the first dose of study intervention.
? A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
11. The participant (or legally acceptable representative) has provided documented informed consent for the study. The participant may also provide consent for Future Biomedical Research (FBR). However, the participant may participate in the study without participating
INDUCTION PERIOD
1.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
2.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
3.Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment
4.Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable
5.Has myelodysplastic syndrome/acute myeloid leukemia or has features suggestive of MDS/AML
6.Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
7.Has active, or a history of, interstitial lung disease
8.Has a known history of active tuberculosis
9.Has an active infection requiring systemic therapy
10.Has a known history of HIV infection
11.Has a known history of Hepatitis B or known active Hepatitis C virus infection
12.Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of first study treatment
13.Has neuropathy =Grade 2
14.Has not recovered from AEs due to a previously administered therapy
15.Has a known history of hypersensitivity or allergy to pembrolizumab, olaparib and any of its components, and/or to any of the study chemotherapies and any of their components
16.Has severe hypersensitivity to the study treatments and/or any of their excipients
17.Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
18.Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 180 days after the last dose of study treatment
19.Is a WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation
20.Has received prior therapy with either olaparib or any other PARP inhibitor
21.Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
22.Has received colony-stimulating factors within 2 weeks prior to the first dose of study treatment
23.Has had an allogenic tissue/solid organ transplant
24.Has received previous allogenic bone marrow transplant or double umbilical cord transplantation
25.Had major surgery within 2 weeks of starting study intervention or has not recovered from any effects of any major surgery
26.Has received a live or live-attenuated vaccine within 30 days prior to first study treatment
27.Is receiving any medication prohibited in combination with study chemotherapies as described in the respective product labels unless medication was stopped within 7 days prior to first study treatment
28.Has received prior therapy with an anti–PD-1, anti–PD-L1, or anti– PD-L2 agent or with an agent directed to another co-inhibitory T cell receptor or has previously participated in a study evaluating pembrolizumab regardless of treatment received
29.Is currently participating in or has participated in a study of an investigational agent or has used an investigational device with
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method