R11 Nausea and vomiting Nausea and vomiting
Conditions
Interventions
Olaparib, tablet 300 mg BID in combination with Pembrolizumab 200mg IV every 3 weeks for 2 years - Olaparib, tablet 300 mg BID in combination with Pembrolizumab 200mg IV every 3 weeks for 2 years
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline or somatic 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. 2.Has either centrally-confirmed known or suspected deleterious mutations in at least 1 of the specified 15 genes involved in HRR (ie, BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L) or centrally-confirmed HRD based on the Lynparza HRR-HRD assay. 3.Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology and confirmed in real time by BICR. BICR must confirm the presence of radiologically measurable disease per RECIST 1.1 for the participant to be eligible for the study. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 4.Has a life expectancy of at least 3 months. 5.Is male or female, who is at least 18 years of age at the time of signing the informed consent. 6.Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of treatment initiation. 7.A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 120 days (4 months), corresponding to time needed to eliminate any study intervention(s) and refrain from donating sperm during this period. Refer to Appendix 5 for additional guidance. 8.A female participant is eligible to participate if she is not pregnant (Appendix 5), not breastfeeding, and at least 1 of the following conditions applies: •Not a woman of childbearing potential (WOCBP) as defined in Appendix 5. OR •A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and for at least 180 days (6 months) after the last dose of study intervention, corresponding to time needed to eliminate any study intervention(s). 9.The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the main study without participating in FBR. 10.Has adequate organ function, as detailed in Table 4 (see Protocol); all screening laboratory tests should be performed within 10 days prior to the first dose of study intervention.
Exclusion criteria
Exclusion criteria: 1.Has a known additional malignancy that is progressing or has required active treatment in the last 3 years. 2.Has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis. 3.Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML. 4.Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. 5.Has an active infection requiring systemic therapy. 6.Has active tuberculosis (Bacillus tuberculosis [TB]). 7.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention. 8.Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 9.Has a history or current evidence of any condition (eg, cytopenia, transfusion-dependent anemia, or thrombocytopenia), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator. 10.Received colony-stimulating factors (eg, 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 intervention. 11.Is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan, uncontrollable bone pain, or any psychiatric disorder that prohibits obtaining informed consent. 12.Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study. 13.Has a known history of human immunodeficiency virus (HIV) infection. Testing for HIV at screening is only required if mandated by local health authority. Refer to Appendix 7 for country-specific requirements. 14.Has known active hepatitis (ie, Hepatitis B or C) •Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. •Participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 15.Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption). 16.A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 17.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, O
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clopper-Pearson Method NAME OF THE RESULT: Objective response rate (ORR) per modified RECIST 1.1a or PCWG-modified RECIST 1.1 (participants with prostate cancer) by BICR PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The primary analysis will be conducted when all enrolled participants have at least 9 months of potential follow-up for Subgroups 1, 2, 3, respectively. The final analysis will be conducted when all enrolled participants have at least 24 months of potential follow-up for each subgroup. | — |
Secondary
| Measure | Time frame |
|---|---|
| Clopper-Pearson Method NAME OF THE RESULT: Objective response rate (ORR) per modified RECIST 1.1a or PCWG-modified RECIST 1.1 (participants with prostate cancer) by BICR PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The primary analysis will be conducted when all enrolled participants have at least 9 months of potential follow-up for Subgroups 1, 2, 3, respectively. The final analysis will be conducted when all enrolled participants have at least 24 months of potential follow-up for each subgroup.;Kaplan Meier Method NAME OF THE RESULT: Duration of response (DOR) per modified RECIST 1.1a or PCWG-modified RECIST 1.1 (participants with prostate cancer) by BICR PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The primary analysis will be conducted when all enrolled participants have at least 9 months of potential follow-up for Subgroups 1, 2, 3, respectively. The final analysis will be conducted when all enrolled participants have at least 24 months of potential follow-up for each subgroup.;Kaplan Meier Method NAME OF THE RESULT: Overall survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The primary analysis will be conducted when all enrolled participants have at least 9 months of potential follow-up for Subgroups 1, 2, 3, respectively. The final analysis will be conducted when all enrolled participants have at least 24 months of potential follow-up for each subgroup.;Kaplan Meier Method NAME OF THE RESULT: Progression-free survival (PFS) per modified RECIST 1.1a or PCWG-modified RECIST 1.1 (participants with prostate cancer) by BICR PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The primary analysis will be conducted when all enrolled participants have at least 9 months of potential follow-up for Subgroups 1, 2, 3, respectively. T | — |
Countries
Australia, Canada, China, Colombia, Estonia, France, Germany, Hungary, Israel, Italy, Japan, Korea North, Korea South, Malasya, Mexico, Poland, Russian Federation, Taiwan, Turkey, Ukraine, United States
Outcome results
None listed