We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (BISCAY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02546661
Recruitment Status : Recruiting
First Posted : September 11, 2015
Last Update Posted : January 4, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

This is an open label, multi-drug, biomarker-directed, multi-centre, multi-arm, randomised Phase 1b study in patients with muscle invasive bladder cancer (urothelial) who have progressed on prior treatment. This study is modular in design, allowing evaluation of the safety, tolerability, pharmacokinetics and anti-tumour activity of multiple agents as monotherapy and as combinations of different novel anti-cancer agents in patients with muscle invasive bladder cancer.

The study will consist of a number of study modules (substudies), each evaluating the safety and tolerability of a specific agent or combination.


Condition or disease Intervention/treatment Phase
Muscle Invasive Bladder Cancer Drug: AZD4547 Drug: Durvalumab Drug: Olaparib Drug: AZD1775 Drug: Vistusertib Drug: AZD9150 Phase 1

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Multi-Centre, Multi-arm Phase 1b Study in Patients With Muscle Invasive Bladder Cancer (MIBC) Who Have Progressed on Prior Treatment (BISCAY).
Actual Study Start Date : October 3, 2016
Estimated Primary Completion Date : April 19, 2019
Estimated Study Completion Date : April 19, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer
Drug Information available for: Durvalumab
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Module A: AZD4547 Monotherapy

AZD4547 will be given orally twice daily until disease progression.

Patients who receive AZD4547 as monotherapy will have the option to cross over to durvalumab as monotherapy at the point of objective progression, as long as the following criteria are met:

  • The investigator believes it is in the patient's interest to receive durvalumab;
  • The patient consents to the continued treatment;
  • It is clinically appropriate for the patient to continue on durvalumab treatment;
  • The patient satisfies the key eligibility criteria for receiving durvalumab treatment.
Drug: AZD4547
AZD4547 Monotherapy vs. Durvalumab + AZD4547 1:1 Randomization.
Experimental: Module A: Durvalumab + AZD4547
AZD4547 will be given orally twice daily until disease progression. Patients will also receive durvalumab by IV infusion once every 4 weeks.
Drug: AZD4547
AZD4547 Monotherapy vs. Durvalumab + AZD4547 1:1 Randomization.
Drug: Durvalumab
Durvalumab
Other Name: MEDI4736
Experimental: Module B: Durvalumab + Olaparib
Durvalumab will be given by IV infusion once every 4 weeks. Olaparib will be given orally twice daily.
Drug: Durvalumab
Durvalumab
Other Name: MEDI4736
Drug: Olaparib
Durvalumab + Olaparib
Experimental: Module C: Durvaluamb + AZD1775
Durvalumab will be given by IV infusion once every 4 weeks. AZD1775 will be given orally in approximate 12 hour intervals over 3 days (6 doses) on Days 1-3, 8-10, and 15-17 of 28 day cycles.
Drug: Durvalumab
Durvalumab
Other Name: MEDI4736
Drug: AZD1775
Durvalumab + AZD1775
Experimental: Module D: Durvalumab monotherapy
Durvalumab will be given by IV infusion once every 4 weeks.
Drug: Durvalumab
Durvalumab
Other Name: MEDI4736
Experimental: Module E: Durvalumab + Vistusertib
Durvalumab will be given by IV infusion once every 4 weeks. Vistusertib will be given orally twice per day on an intermittent schedule (2 days on, 5 days off).
Drug: Durvalumab
Durvalumab
Other Name: MEDI4736
Drug: Vistusertib
Durvalumab + Vistusertib
Experimental: Module F: Durvaluamb + AZD9150
AZD9150 will be given as monotherapy on Days -7, -5, and -3 of a one week lead-in period. Combination dosing with IV AZD9150 followed by IV Durvalumab begins on Day 1 of each 28 day cycle. Thereafter AZD9150 is given weekly and Durvalumab is given once every 4 weeks.
Drug: Durvalumab
Durvalumab
Other Name: MEDI4736
Drug: AZD9150
Durvalumab + AZD9150


Outcome Measures

Primary Outcome Measures :
  1. The frequency and nature of adverse events related to AZD4547 monotherapy. [ Time Frame: Adverse events will be assessed at each clinic visit up to 12 weeks, and at study discontinaution and 90 days after the end of treatment. ]
    The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of AZD4547 monotherapy given orally to selected patients with MIBC who have progressed following prior therapy.

  2. The frequency and nature of adverse events related to the combination of intravenous durvalumab and oral AZD4547. [ Time Frame: Adverse events will be assessed at each clinic visit up to 12 weeks, and at study discontinaution and 90 days after the end of treatment. ]
    The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of durvalumab given intravenously in combination with AZD4547 given orally to selected patients with MIBC who have progressed following prior therapy.

  3. The frequency and nature of adverse events related to the combination of intravenous durvalumab and oral olaparib. [ Time Frame: Adverse events will be assessed at each clinic visit up to 12 weeks, and at study discontinaution and 90 days after the end of treatment. ]
    The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of durvalumab given intravenously in combination with olaparib given orally to selected patients with MIBC who have progressed following prior therapy.

  4. The frequency and nature of adverse events related to intravenous durvalumab when given in combination with oral AZD1775. [ Time Frame: Adverse events will be assessed at each clinic visit up to 12 weeks, and at study discontinaution and 90 days after the end of treatment. ]
    The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of durvalumab given intravenously in combination with AZD1775 given orally to selected patients with MIBC who have progressed following prior therapy.

  5. The frequency and nature of adverse events related to intravenous durvalumab monotherapy. [ Time Frame: Adverse events will be assessed at each clinic visit up to 12 weeks, and at study discontinaution and 90 days after the end of treatment. ]
    The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of durvalumab monotherapy given intravenously to selected patients with MIBC who have progressed following prior therapy.

  6. The frequency and nature of adverse events related to intravenous durvalumab when given in combination with oral vistusertib. [ Time Frame: Adverse events will be assessed at each clinic visit up to 12 weeks, and at study discontinaution and 90 days after the end of treatment. ]
    The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of durvalumab given intravenously in combination with vistusertib given orally to selected patients with MIBC who have progressed following prior therapy.

  7. Change from baseline in clinical chemistry parameters. [ Time Frame: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation. ]
    Changes from baseline in clinical chemistry parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.

  8. Change from baseline in haematology parameters. [ Time Frame: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation. ]
    Changes from baseline in haemotology parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.

  9. Change from baseline in urinalysis results. [ Time Frame: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation. ]
    Changes from baseline in urinalysis findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.

  10. Change from baseline in vital signs. [ Time Frame: Day 1 of Cycles 1, 2, 3, and 4 and every 4 weeks therafter, and at discontinuation. ]
    Changes from baseline in vital signs will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.

  11. Change from baseline in physical examination findings. [ Time Frame: Day 1 of Cycles 1, 2, 3, and 4 and every 4 weeks therafter, and at discontinuation. ]
    Changes from baseline in physical examination findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.

  12. Change from baseline in ECG findings. [ Time Frame: ECGs will be collected at screening, Day 1, Cycle 1and then Day 1 of each cycle from Cycle 2 onwards. ]
    Changes from baseline in ECG findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.

  13. Change from baseline in ejection fraction determined by assessing ECHO/MUGA scans. [ Time Frame: Ejection fraction will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter. ]
    Changes from baseline in ejection fraction determined by assessing ECHO/MUGA scans will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.

  14. The frequency and nature of adverse events related to the combination of intravenous durvalumab and intravenous AZD9150. [ Time Frame: Adverse events will be assessed at each clinic visit up to 12 weeks, and at study discontinaution and 90 days after the end of treatment. ]
    The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of intravenous durvalumab in combination with intravenous AZD9150 in selected patients with MIBC who have progressed following prior therapy.


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 16 weeks and 24 weeks ]

    The percentage of patients who have a confirmed visit response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator per RECIST 1.1.

    Data obtained up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR.


  2. Disease control rate (DCR) [ Time Frame: 16 weeks and 24 weeks ]
    The percentage of patients who have a confirmed visit response of CR or PR or stable disease (SD) as assessed by the investigator per RECIST 1.1.

  3. Progression free survival (PFS) [ Time Frame: 1, 2, 3, and 4 months after the first dose of study drug. ]
    The time from randomization until the date of objective disease progression or death (from any cause in the absence of progression) regardless of whether the patient withdraws from assigned therapy or receives another anticancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.

  4. Duration of response (DoR) [ Time Frame: up to 12 months ]
    Duration of overall response will be analysed using Kaplan-Meier methods, where patients who do not progress before dying will be censored at the time of death or at the administrative end of the study.

  5. Plasma concentration of AZD4547 (Module A) [ Time Frame: Blood samples will be taken pre-dose on Days 1 and 8 of Cycle 1; pre-dose and 2, 3, 4 and 6 hours post-dose on Day 1 of Cycle 2; and pre-dose and 2 to 4 hours post-dose on Day 1 of Cycle 3. ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  6. Plasma concentration of durvalumab (Module A) [ Time Frame: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and for the post-Cycle 7 8-weekly assessments, and pre-dose for Day 8 of Cycle 1. ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  7. Plasma concentration of olaparib (Module B) [ Time Frame: Blood samples will be taken on Day 3 of Cycles 1 and pre-dose and 4 hr post-dose. Serial samples on Day 3 of Cycle 3, pre-dose, 1, 2, 4, 6, 8, and 10 hr post-dose. ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  8. Plasma concentration of AZD1775 (Module C) [ Time Frame: Blood samples will be taken on Day 8 at steady state at the following time points: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hr post-dose. ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  9. Plasma concentration of durvalumab (Module C) [ Time Frame: Blood samples will be taken on Days 1 and 8 of Cycle 1 pre-dose and at the end of infusion (1 hour). Samples will also be collected on Day 1 of Cycles 2 to 7 pre-dose and at the end of infusion. ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  10. Plasma concentration of durvalumab (Module D) [ Time Frame: Blood samples will be taken on Days 1 and 8 of Cycle 1 ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  11. Plasma concentration of vistusertib (Module E) [ Time Frame: Blood samples will be collected pre-dose, and 2 and 4 hr post-dose on Day 1 of Cycle 1; and pre-dose and 2 to 6 hr post-dose (matched to biopsy) on Day 2 of Cycle 2. ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  12. Plasma concentration of durvalumab (Module E). [ Time Frame: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and every 8 weeks thereafter and pre-dose for Day 8 of Cycle 1. ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  13. Plasma concentration of AZD9150 (Module F) [ Time Frame: Blood samples will be taken pre-dose of Days -7, -5, and -3 of the lead-in portion and thereafter prior to dosing and at the ned of infusion on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (approximately 8 months). ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  14. Plasma concentration of durvalumab (Module F). [ Time Frame: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and every 8 weeks thereafter and pre-dose for Day 8 of Cycle 1. ]
    The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.

  15. The presence of Anti-Drug Antibodies (ADA) and ADA neutralising antibodies to durvaluamb will be assessed in patients receiving durvalumab in any sub-study module. [ Time Frame: Blood samples will be collected prior to durvalumab doing on Day 1 of Cycles 1, 2 and 4 and every 12 weeks thereafter (up to 12 months). ]
    The formation of anti-drug antibodies and neutralizing antibodies will be assessed by validated methods.


Other Outcome Measures:
  1. Mutation status of cancer associated genes in circulating tumour DNA (ctDNA). [ Time Frame: Blood samples for assessment of ctDNA will be collected at screening, on Day 1 of Cycles 1, 2, 3, and 4 (up to 91 days) and at disease progression. ]
    Plasma and serum samples will be collected and assessed for circulating tumour DNA to explore the mutation status of cancer associated genes.

  2. Biomarker Analysis of Blood and Tissue [ Time Frame: Up to 12 months ]

    Biomarker analysis of blood and tissue to assess exploratory markers, which may include but is not limited to:

    • immune cell gene expression profiles and cytokine profiles within the peripheral and tumoural compartments,
    • the presence of IFN-γ, tumour necrosis factor-α, IL-2, IL-6, IL-10, IL-8, and IL-12 as well as antibodies against tumour, self, or viral antigens,
    • expression of PD-L1,
    • CD8 and the number and phenotype of immune cells such as T-cells.

    Markers relevant to the targeted therapy, for example FGFR and ligand expression and PD markers, for example pErk, pS6 and γH2AX will also be measured in tumour paired biopsy samples.

    Biomarker assessments that may have the potential to identify patients likely to respond to treatment with the agents studied in this modular protocol will be investigated to determine a patient's biomarker status and for possible correlation with efficacy endpoints.



Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for all Modules:

  1. Metastatic MIBC
  2. 2nd/3rd line
  3. Failed adjuvant/neo-adjuvant chemotherapy <1 yr
  4. 1 lesion ≥10 mm at baseline in the longest diameter suitable for accurate repeated measurement
  5. WHO perf. status 0-1

For Module A:

  1. M/F ≥25
  2. Confirmation of FGFR3 mutation or FGFR fusion

For Module B:

  1. Hgb ≥10 g/dL
  2. Deleterious mutation, deletion or truncation in any HRR genes

For Module C:

1. Tumour harbours a deletion or inactivating mutation of the CDKN2A or RB1 genes and/or amplification of CCNE1, MYC, MYCL or MYCN genes

For Module E:

1. Contraception must be sustained throughout treatment with vistusertib and 16 wks after last dose

For Module F:

  1. Adequate organ and marrow function, defined as Leukocytes ≥3.0x10(exp9)/L; ANC ≥1.5x10(exp9)/L; platelets ≥100x10(exp9)/L
  2. Contraceptive measures must be sustained throughout treatment with AZD9150 and for 180 days after the last dose.

Exclusion Criteria for all Modules:

  1. Immunotherapy, chemotherapy, anticancer agents, radiotherapy <4 wks, or radiotherapy for palliation <2 wks, any study drugs <30 days.
  2. Major surgery <4 wk
  3. Unresolved toxicities from prior therapy
  4. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy
  5. Immunosuppressive drugs <28 days
  6. Any of the following: Autoimmune disease ≤2 yr; IBD; primary immunodeficiency; organ transplant requiring immunosuppressives
  7. Spinal cord compression or brain metastases, treated and stable & not requiring steroids for at least 4 weeks
  8. Severe or uncontrolled systemic disease
  9. Any of the following: Mean QTc ≥470 ms; abnormalities in resting ECG; factors that increase the risk of QTc prolongation or arrhythmia; uncontrolled hyper/hypotension; LVEF <55%; atrial fibrillation; NYHA Grade II-IV; severe valvular disease; uncontrolled angina; stroke/TIA <6 months; acute coronary syndrome <6 months
  10. Any of the following laboratory values: ANC <1.5x10(exp9)/L; Platelets <100x10(exp9)/L; Hgb <9.0 g/dL; ALT >2.5xULN or >5xULN with liver mets; Total bilirubin >1.5 times ULN or with Gilbert's disease ≥2×ULN; Creatinine >1.5xULN concurrent with creatinine clearance <50 mL/min; Corrected Ca >ULN, PO4 >ULN
  11. Active infection including tuberculosis, hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus. Patients with a past or resolved HBV infection are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  12. Live attenuated vaccination <30 days

For Module A:

  1. Prior exposure to: Nitrosourea or mitomycin C <6 weeks; any agent with FGFR inhibition as its primary pharmacology; AZD4547; potent inhibitors/inducers of CYP3A4, inhibitors of CYP2D6 or substrates of CYP3A4 <2 wks
  2. Ophthalmological criteria: RPED; laser treatment or intraocular injection for macular degeneration; age-related macular degeneration; retinal vein occlusion; retinal degenerative disease; other clinically relevant chorioretinal defect
  3. Refractory nausea/vomiting, chronic GI diseases, or previous bowel resection

For Module B:

  1. Transfusion <120 days
  2. Concurrent medications that are strong inhibitors of cytochrome P450 (CYP) 3A (CYP3A) or strong inducers of CYP3A4.
  3. Previous treatment with PARP inhibitor, including olaparib
  4. Patients with history of MDS or AML

For Module C:

  1. Prior exposure to any of the following: Nitrosourea or mitomycin C <6 wks; any agent with Wee1 inhibition as its primary pharmacology; prior treatment with AZD1775
  2. Any drugs or products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with narrow therapeutic index, or moderate to strong inhibitors/inducers of CYP3A4
  3. Herbal preparations
  4. Refractory nausea and vomiting or chronic GI diseases
  5. Cardiac disease <6 months

For Module E:

  1. Minor surgery <14 days of first dose
  2. Exposure to specific substrates of OATP1B1, OATP1B3, MATE1 and MATE2K <5x half-life before treatment. Exposure to strong/moderate inhibitors/inducers of CYP3A4/5, Pgp (MDR1) and BRCP if taken within washout periods before the first dose
  3. Haemopoietic growth factors (filgrastim, sargramostim, GM-CSF) <14 days prior to treatment
  4. Other mTOR inhibitors
  5. Renal disease or renal tubular acidosis
  6. Uncontrolled Type 1 or 2 diabetes

For Module F:

1. AST ≤ 2.5xULN or ≤5xULN with liver mets

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02546661


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Location Service 1-877-400-4656 astrazeneca@emergingmed.com

  Show 31 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Thomas Powles, MBBS, MRCP, MD Barts Cancer Center, Barts and The London School of Medicine and Denistry
Principal Investigator: Hendrik-Tobias Arkenau, MD, PhD Sarah Cannon Research Institute, UK
More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02546661     History of Changes
Other Study ID Numbers: D2615C00001
GU 118 ( Other Identifier: Sarah Cannon Development Innovations )
BISCAY ( Other Identifier: Sponsor )
First Posted: September 11, 2015    Key Record Dates
Last Update Posted: January 4, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Durvalumab
Olaparib
Vistusertib
Muscle invasive bladder cancer
MIBC
BISCAY
MEDI4736
AZD4547
AZD2281
AZD1775
AZD2014
AZD9150

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Antibodies, Monoclonal
Olaparib
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents