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AZD9150 Plus Durvalumab Alone or in Combination With Chemotherapy in Patients With Advanced, Solid Tumours and in Patients With Non-Small-Cell Lung Cancer

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03421353
Recruitment Status : Active, not recruiting
First Posted : February 5, 2018
Last Update Posted : October 20, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a phase Ib/II, open-label multicentre study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of AZD9150 plus durvalumab alone or in combination with chemotherapy in patients with advanced, solid tumours and subsequently in patients with non-small-cell lung cancer (NSCLC).

Condition or disease Intervention/treatment Phase
Advanced Solid Tumours Drug: AZD9150 Drug: Durvalumab Drug: Cisplatin Drug: 5-Flourouracil Drug: Carboplatin Drug: Gemcitabine Drug: Nab-paclitaxel Phase 1

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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II, Open-Label, Multicentre Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9150 Plus Durvalumab Alone or in Combination With Chemotherapy in Patients With Advanced, Solid Tumours and Subsequently in Patients With Non-Small-Cell Lung Cancer
Actual Study Start Date : February 7, 2018
Actual Primary Completion Date : January 17, 2020
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Arm A1
Patients will receive AZD9150 every two weeks (Q2W) + durvalumab every four weeks (Q4W). There will be a 1 week AZD9150 lead-in prior to durvalumab dosing.
Drug: AZD9150

AZD9150 will be administered as a 1-hour intravenous infusion either weekly (QW) or every two weeks (Q2W), depending on which arm the patient is enrolled in.

AZD9150 will be provided as a liquid drug product in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.


Drug: Durvalumab

Durvalumab will be administered as a 1-hour intravenous infusion either every three weeks (Q3W) or every four weeks (Q4W), depending on which arm the patient is enrolled in.

Durvalumab will be provided as a solution in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.

Other Name: MEDI4736

Experimental: Arm A2
Patients will receive AZD9150 once weekly (QW) + durvalumab every three weeks (Q3W) + Cisplatin on Day 1 + 5-flourouracil (5-FU) on Days 1 to 4. This regimen will be repeated every 3 weeks for up to 18 weeks. There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing.
Drug: AZD9150

AZD9150 will be administered as a 1-hour intravenous infusion either weekly (QW) or every two weeks (Q2W), depending on which arm the patient is enrolled in.

AZD9150 will be provided as a liquid drug product in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.


Drug: Durvalumab

Durvalumab will be administered as a 1-hour intravenous infusion either every three weeks (Q3W) or every four weeks (Q4W), depending on which arm the patient is enrolled in.

Durvalumab will be provided as a solution in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.

Other Name: MEDI4736

Drug: Cisplatin
Cisplatin will be infused over 30-60 minutes on Day 1.

Drug: 5-Flourouracil
5-flourouracil will be continuously infused over Days 1 to 4 every three weeks for up to 18 weeks.
Other Name: 5-FU

Experimental: Arm A3
Depending on the results of Arm A2, Arm A3 may not be conducted. If Arm A3 is conducted, patients will receive AZD9150 every two weeks (Q2W) + durvalumab every three weeks (Q3W) + cisplatin on Day 1 + 5-flourouracil (5-FU) over Days 1 to 4. This regimen will be repeated every 3 weeks for up to 18 weeks. There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing.
Drug: AZD9150

AZD9150 will be administered as a 1-hour intravenous infusion either weekly (QW) or every two weeks (Q2W), depending on which arm the patient is enrolled in.

AZD9150 will be provided as a liquid drug product in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.


Drug: Durvalumab

Durvalumab will be administered as a 1-hour intravenous infusion either every three weeks (Q3W) or every four weeks (Q4W), depending on which arm the patient is enrolled in.

Durvalumab will be provided as a solution in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.

Other Name: MEDI4736

Drug: Cisplatin
Cisplatin will be infused over 30-60 minutes on Day 1.

Drug: 5-Flourouracil
5-flourouracil will be continuously infused over Days 1 to 4 every three weeks for up to 18 weeks.
Other Name: 5-FU

Experimental: Arm A4

Patients will receive AZD9150 every two weeks (Q2W) + durvalumab every three weeks (Q3W) + gemcitabine on Days 1 and 8. This regimen will be repeated every 3 weeks. In addition, the following will be added to the regimen:

  • For cisplatin-eligible patients: cisplatin on Day 1 (every 3 weeks for up to 12-18 weeks); or
  • For cisplatin ineligible patients: carboplatin on Day 1 and Day 8 (every 3 weeks for up to 12-18 weeks).

There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing.

Drug: AZD9150

AZD9150 will be administered as a 1-hour intravenous infusion either weekly (QW) or every two weeks (Q2W), depending on which arm the patient is enrolled in.

AZD9150 will be provided as a liquid drug product in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.


Drug: Durvalumab

Durvalumab will be administered as a 1-hour intravenous infusion either every three weeks (Q3W) or every four weeks (Q4W), depending on which arm the patient is enrolled in.

Durvalumab will be provided as a solution in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.

Other Name: MEDI4736

Drug: Cisplatin
Cisplatin will be infused over 30-60 minutes on Day 1.

Drug: Carboplatin
Carboplatin will be infused over 30 to 60 minutes on Days 1, 8, and 15, depending on which arm the patient is enrolled in, for up to 18 weeks.

Drug: Gemcitabine
Gemcitabine will be infused over 30 minutes on Days 1 and 8 for up to 18 weeks.

Experimental: Arm A5
Patients will receive AZD9150 every two weeks (Q2W) plus durvalumab every three weeks (Q3W) plus carboplatin on Day 1 plus nab-paclitaxel on Days 1, 8, and 15 (every 3 weeks for up to 12-18 weeks). There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing.
Drug: AZD9150

AZD9150 will be administered as a 1-hour intravenous infusion either weekly (QW) or every two weeks (Q2W), depending on which arm the patient is enrolled in.

AZD9150 will be provided as a liquid drug product in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.


Drug: Durvalumab

Durvalumab will be administered as a 1-hour intravenous infusion either every three weeks (Q3W) or every four weeks (Q4W), depending on which arm the patient is enrolled in.

Durvalumab will be provided as a solution in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.

Other Name: MEDI4736

Drug: Carboplatin
Carboplatin will be infused over 30 to 60 minutes on Days 1, 8, and 15, depending on which arm the patient is enrolled in, for up to 18 weeks.

Drug: Nab-paclitaxel
Nab-paclitaxel will be infused over 30 to 40 minutes on Days 1, 8, and 15 for up to 18 weeks.

Experimental: Arm D: AZD9150 SC
Part D will compare the single and steady state pharmacokinetics of AZD9150 given subcutaneously (SC) QW to AZD9150 given by IV QW in combination with durvalumab 1500 mg Q4W. Patients will be randomly assigned to either SC or IV AZD9150.
Drug: AZD9150

AZD9150 will be administered as a 1-hour intravenous infusion either weekly (QW) or every two weeks (Q2W), depending on which arm the patient is enrolled in.

AZD9150 will be provided as a liquid drug product in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.


Drug: Durvalumab

Durvalumab will be administered as a 1-hour intravenous infusion either every three weeks (Q3W) or every four weeks (Q4W), depending on which arm the patient is enrolled in.

Durvalumab will be provided as a solution in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.

Other Name: MEDI4736

Experimental: Arm D: AZD9150 IV
Part D will compare the single and steady state pharmacokinetics of AZD9150 given subcutaneously (SC) QW to AZD9150 given by IV QW in combination with durvalumab 1500 mg Q4W. Patients will be randomly assigned to either SC or IV AZD9150.
Drug: AZD9150

AZD9150 will be administered as a 1-hour intravenous infusion either weekly (QW) or every two weeks (Q2W), depending on which arm the patient is enrolled in.

AZD9150 will be provided as a liquid drug product in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.


Drug: Durvalumab

Durvalumab will be administered as a 1-hour intravenous infusion either every three weeks (Q3W) or every four weeks (Q4W), depending on which arm the patient is enrolled in.

Durvalumab will be provided as a solution in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement.

Other Name: MEDI4736




Primary Outcome Measures :
  1. Part A: Maximum Tolerated Dose (MTD) in subjects receiving AZD9150 plus durvalumab and AZD9150 plus durvalumab plus chemotherapy. [ Time Frame: Through study completion (an average of 6 months). Dose-limiting toxicities (DLTs) will be assessed through 5 weeks for patients who do not receive chemotherapy or 3 weeks for patients receiving chemotherapy. ]
    The Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) will be determined by assessment of the incidence of dose-limiting toxicities (DLTs). DLTs may come from the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), the change from baseline in vital signs, clinical chemistry, haemotology, and urinalysis parameters will be evaluated for each treatment arm in Part A of the study.

  2. Part D: Area under the plasma concentration versus time curve at steady state [AUC(ss)] of AZD9150 administered once per week in combination with durvalumab. [ Time Frame: Blood samples for the PK analysis of AZD9150 will be collected at prespecified intervals during Weeks 0, 1, 5, 6, and 9. ]
    Pharmacokinetic parameters will be derived from the measured plasma concentration of AZD9150. The area under the plasma concentration versus time curve [AUC(ss)] will be compared in subjects receiving AZD9150 subcutaneoulsy vs. intravenously.

  3. Part D: Minimum plasma concentration at steady state [Ctrough (ss)] of AZD9150 administered once per week in combination with durvalumab. [ Time Frame: Blood samples for the PK analysis of AZD9150 will be collected at prespecified intervals during Weeks 0, 1, 5, 6, and 9. ]
    Pharmacokinetic parameters will be derived from the measured plasma concentration of AZD9150. The minimum plasma concentration of AZD9150 at steady state [Ctrough(ss)] will be determined for subjects receiving AZD9150 once per week in combination with durvalumab.


Secondary Outcome Measures :
  1. Part A: Disease Control Rate (DCR) [ Time Frame: 12 weeks ]
    Efficacy parameters as defined by RECIST v1.1 for each combination (with and without chemotherapy) and schedule include: disease control rate (DCR) at 12 weeks, duration of overall response (DOR), and progression-free survival (PFS).

  2. Part A: Duration of Overall Response (DoR) [ Time Frame: Throughout the study (approximately 6 months). ]
    Efficacy parameters as defined by RECIST v1.1 for each combination (with and without chemotherapy) and schedule include: disease control rate (DCR) at 12 weeks, duration of overall response (DOR), and progression-free survival (PFS).

  3. Part A: Progression-Free Survival (PFS) [ Time Frame: From the date of documented complete response or partial response, whichever comes first, until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months ]
    Efficacy parameters as defined by RECIST v1.1 for each combination (with and without chemotherapy) and schedule include: disease control rate (DCR) at 12 weeks, duration of overall response (DOR), and progression-free survival (PFS).

  4. Part A: AZD9150 anti-drug antibody titres [ Time Frame: Blood samples for AZD9150 anti-drug antibodies (ADAs) will be collected predose on prespecified dosing days up to 9 weeks. ]
    Unwanted immunogenicity in the form of anti-drug-antibodies (ADAs) will be assessed.

  5. Part A: Durvalumab anti-drug antibody titres [ Time Frame: Blood samples for durvalumab anti-drug antibodies (ADAs) will be collected predose on prespecified dosing days up to 13 weeks. ]
    Unwanted immunogenicity in the form of anti-drug-antibodies (ADAs) will be assessed.

  6. Part A: Baseline tumour PD-L1 expression [ Time Frame: Pre-dose ]

    Baseline tumour PDL1 expression will be evaluated for potential correlation with drug activity or the ability to prospectively identify patients likely to respond to treatment.

    Immunohistochemistry (IHC) for PD-L1 will be carried out using a tumour sample from an archival biopsy or one taken at screening.


  7. Part A: STAT3 protein in tumour biopsies [ Time Frame: Predose and 3 weeks after start of treatment ]
    STAT3 knockdown will be assessed in tumour biopsies taken on-treatment at Week 3, Day 1. Baseline and on-treatment biopsies will be used to measure STAT3 expression levels by immunohistochemistry.

  8. Part A: Peak plasma concentration (Cmax) of AZD9150 after single-dose. [ Time Frame: Blood samples for the PK analysis of AZD9150 will be collected at prespecified intervals during Weeks 0, 1, 5, 6, and 9. ]
    The peak plasma concentration (Cmax) of AZD9150 after single dose and at steady state after multiple doses in combination with durvalumab Q4W will be determined.

  9. Part A: Trough plasma concentration (Ctrough) of AZD9150 after single-dose. [ Time Frame: Blood samples for the PK analysis of AZD9150 will be collected at prespecified intervals during Weeks 0, 1, 5, 6, and 9. ]
    The trough plasma concentration (Ctrough) of AZD9150 after single dose and at steady state after multiple doses in combination with durvalumab Q4W will be determined.

  10. Part A: Peak plasma concentration (Cmax,ss) of AZD9150 after multiple doses. [ Time Frame: Blood samples for the PK analysis of AZD9150 will be collected at prespecified intervals during Weeks 0, 1, 5, 6, and 9. ]
    The peak plasma concentration (Cmax,ss) of AZD9150 at steady state after multiple doses in combination with durvalumab Q4W will be determined.

  11. Part A: Trough plasma concentration (Ctrough,ss) of AZD9150 after multiple doses. [ Time Frame: Blood samples for the PK analysis of AZD9150 will be collected at prespecified intervals during Weeks 0, 1, 5, 6, and 9. ]
    The trough plasma concentration (Ctrough,ss) of AZD9150 at steady state after multiple doses in combination with durvalumab Q4W will be determined.

  12. Part A: Area under the plasma concentration versus time curve (AUC) of AZD9150 after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The area under the plasma concentration versus time curve (AUC) of AZD9150 after single-dose given in combination with durvalumab Q4W will be determined.

  13. Part A: Area under the plasma concentration versus time curve [AUC(ss)] at steady state after multiple doses. [ Time Frame: Through study completion (an average of 6 months) ]
    The area under the plasma concentration versus time curve [AUC(ss)] of AZD9150 at steady state after multiple in combination with durvalumab Q4W will be determined.

  14. Part D: Injection site tolerability for patients receiving subcutaneous injections. [ Time Frame: Through study completion (an average of 6 months) ]
    Pain, tenderness, redness, and other symptoms will be assessed for subcutaneous injection of AZD9150.

  15. Part D: The incidence of adverse events (AEs) in subjects receiving AZD9150. [ Time Frame: Through study completion (an average of 6 months) ]
    The incidence of adverse events will be determined for each treatment arm in Part D of the study.

  16. Part D: The incidence of serious adverse events (SAEs) in subjects receiving AZD9150. [ Time Frame: Through study completion (an average of 6 months) ]
    The incidence of serious adverse events will be determined for each treatment arm in Part D of the study.

  17. Part D: Peak plasma concentration (Cmax) of AZD9150 after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The peak plasma concentration (Cmax) of AZD9150 after single dose and at steady state after multiple doses when given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  18. Part D: Peak plasma concentration (Cmax,ss) of AZD9150 at steady state after multiple doses. [ Time Frame: Through study completion (an average of 6 months) ]
    The peak plasma concentration (Cmax) of AZD9150 after single dose and at steady state after multiple doses when given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  19. Part D: Time to peak plasma concentration (tmax) of AZD9150 after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The time to peak plasma concentration (tmax) of AZD9150 after single dose when given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  20. Part D: Area under the plasma concentration versus time curve [AUC(0-inf)] after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The area under the plasma concentration versus time curve from zero time to infinity [AUC(0-inf)] of AZD9150 after single dose given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  21. Part D: Area under the plasma concentration versus time curve [AUC(ss)] at steady state after multiple doses. [ Time Frame: Through study completion (an average of 6 months) ]
    The area under the plasma concentration versus time curve [AUC(ss)] of AZD9150 at steady state after multiple doses given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  22. Part D: Area under the plasma concentration versus time curve [AUC(0-t)] after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The area under the plasma concentration versus time curve from zero time to time t [AUC(0-t)] of AZD9150 after single dose given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  23. Part D: Area under the plasma concentration versus time curve from time zero to 48 hours [AUC(0-48] after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The area under the plasma concentration versus time curve from zero time to 48 hours [AUC(0-48)] of AZD9150 after single dose given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  24. Part D: The systemic clearance (CL) of AZD9150 after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The systemic clearance (CL) after single-dose will be calculated for AZD9150 given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  25. Part D: The systemic clearance [CL(ss)] of AZD9150 after multiple doses. [ Time Frame: Through study completion (an average of 6 months) ]
    The systemic clearance [CL(ss)] after multiple doses will be calculated for AZD9150 given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  26. Part D: The apparent systemic clearance (CL/F) of AZD9150 after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The apparent systemic clearance (CL/F) after single-dose will be calculated for AZD9150 given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  27. Part D: The volume of distribution (Vz/F) of AZD9150 after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The volume of distribution (Vz/F) after single-dose will be calculated for AZD9150 given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  28. Part D: The mean residence time (MRT) of AZD9150 after single-dose. [ Time Frame: Through study completion (an average of 6 months) ]
    The mean residence time (MRT) after single-dose will be calculated for AZD9150 given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  29. Part D: The elimination half-life (t1/2) of AZD9150 after single-dose [ Time Frame: Through study completion (an average of 6 months) ]
    The elimination half-life (t1/2) after single-dose will be calculated for AZD9150 given subcutaneously QW relative to intravenous administration QW in combination with durvalumab Q4W will be determined.

  30. Part D: Injection site tolerability of AZD9150 given by subcutaneous injection every 4 weeks relative to AZD9150 200 mg IV QW in [ Time Frame: Through study completion (an average of 6 months) ]
    Injection site tolerability will be assessed by careful visual observation of both subcutaneous and intravenous injection sites and questioning the patient about adverse events at the injection site.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Subjects are eligible to be included in the study only if all of the following inclusion criteria and none of the exclusion criteria apply.

  1. Signed and dated informed consent. For inclusion in the optional pharmacogenetic research, patients must provide informed consent for the genetic sampling and analyses.
  2. ≥ 18 years of age.
  3. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  4. Minimum life expectancy of 12 weeks
  5. Part A of the study will include patients that have histological confirmation of a solid malignancy [other than Hepatocellular Carcinoma (HCC)] that is refractory to standard therapy or for which no standard of care regimen currently exists.
  6. Part D of the study will include patients with histological confirmation of a solid malignancy (other than HCC) that are refractory to standard therapy of for which no standard of care regimen currently exists.
  7. Willing to undergo mandatory biopsy at screening and on treatment. Part A only: the first 3 subjects in each arm are exempt from this requirement. Patients in Part D are exempt from this biopsy requirement.
  8. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes that must have short axis ≥15 mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) that is suitable for accurate repeated measurements.
  9. Females should be using adequate contraceptive measures, should not be breast feeding, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:

    • Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
    • Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinising hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
    • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation.
  10. Male patients must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 20 weeks after the last dose of study treatments.

Exclusion Criteria

Patients should not enter the study if any of the following exclusion criteria are fulfilled.

  1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca and/or Sarah Cannon Development Innovations staff and/or staff at the study site).
  2. Previous enrolment in the present study.
  3. Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng. Patients should stop using herbal medications 7 days prior to the first dose of study treatment.
  4. Brain metastases or spinal cord compression unless asymptomatic and not requiring steroids for at least 14 days prior to start of study treatment.
  5. With the exception of alopecia and haemoglobin (Hb) ≥ 9 mg/dL and < 10 mg/dL, any unresolved toxicities from prior therapy CTCAE Grade > 1 at the time of starting study treatment.
  6. Active interstitial lung disease (ILD)/pneumonitis or a prior history of ILD/pneumonitis requiring treatment with steroids.
  7. Patients receiving any concurrent chemotherapy, radiotherapy, immunotherapy, or biologic, or hormonal therapy for cancer.

    • Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable. The dose of systemic corticosteroids must not exceed 10 mg of prednisone equivalent.
    • Patients in Part A and Part D with radically-treated prostate cancer may continue androgen deprivation therapy (ADT).
  8. Patients must have completed any previous cancer-related treatments before enrolment. The following intervals between the end of the prior treatment and first dose of study drug must be observed:

    • Port-a-cath placement: no waiting is required
    • Minor surgical procedures (as defined by the Medical Monitor): 7 postoperative days
    • Major surgery (as defined by the Medical Monitor): ≥4 weeks
    • Radiotherapy: ≥4 weeks (patients who receive palliative radiation for nontarget tumour lesions need not be subjected to this washout period and can be enrolled immediately)
    • Chemotherapy: ≥ 21 days or 5 half-lives (whichever is longer) from the first dose of study drug
    • Immunotherapy and/or anticancer therapy with agents including mAbs ≥4 weeks
    • Current or prior use of immunosuppressive medication within 14 days before first dose of durvalumab The following are exceptions to this criterion:

      • Use of intranasal, inhaled, topical corticosteroids, local steroid injections (e.g., intra articular injections)
      • Systemic corticosteroids at physiologic doses below 10 mg/day of prednisone or equivalent is permitted
      • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are permitted
  9. For Part A and Part D patients who have received more than 3 prior cytoreductive chemotherapy regimens.
  10. Has active or prior documented autoimmune disease within the past 2 years with the exceptions of vitiligo, Graves' Disease, and/or psoriasis not requiring systemic treatment
  11. Has active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  12. Has a history of primary immunodeficiency
  13. Has undergone an organ transplant that requires use of immunosuppressive treatment
  14. Any of the following cardiac criteria:

    • Mean resting corrected QT interval (QTc) calculated using Fridericia's formula (QTcF) of >450 msec for males and >470 msec for females obtained from 3 electrocardiograms (ECGs) taken over 5 minutes
    • Any clinically important abnormalities in rhythm, conduction or morphology of a resting ECG, e.g., complete left bundle branch block, third degree heart block, that in the opinion of the Investigator renders the patient unsuitable for participation in the study
    • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age
    • Any concomitant medication with known or possible risk of prolonging the QT interval.
  15. Inadequate organ and marrow function as demonstrated by any of the following laboratory values. Transfusions intended to elevate any parameters below solely for the intent of meeting study eligibility are not permitted.

    • Leukocytes <3.0 x 10(exp 9)/L
    • Absolute neutrophil count <1.5 x 10(exp 9)/L
    • Platelet count <100 x 10(exp 9)/L
    • Haemoglobin <90 g/L
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
    • Total bilirubin >1.5 times ULN if no liver metastases or 3 times ULN in the presence of liver metastases or documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia)
    • Creatinine outside normal limits OR, if creatinine outside normal limits, a creatinine clearance <60 mL/min (measured by 24-hour urine collection or calculated by Cockcroft and Gault equation (Cockcroft and Gault 1976).
  16. Has a history of allergic reactions attributed to the study treatments (AZD9150 or durvalumab), assigned chemotherapy agents, their compounds, or agents of similar chemical or biologic composition (e.g., antibody therapeutics)
  17. Suffers from a comorbidity that in the opinion of the Investigator or Medical Monitor renders the patient unsuitable for participation in the study. Such comorbidity may include, but is not limited to, uncontrolled intercurrent illness such as active infection, severe active peptic ulcer disease or gastritis, myocardial infarction within 6 months before entry, congestive heart failure, symptomatic congestive heart failure, active cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
  18. As judged by the Investigator, has any evidence of severe or uncontrolled diseases, or has an active viral infection of human immunodeficiency virus (HIV), human papilloma virus (HPV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV)].
  19. Active infection including tuberculosis (clinical evaluation that included clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice).
  20. Has received a live attenuated vaccine within 28 days before the first dose of study drug
  21. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

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): NCT03421353


Locations
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United States, Indiana
Research Site
Lafayette, Indiana, United States, 47905
United States, Oklahoma
Research Site
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37203
United States, Texas
Research Site
Dallas, Texas, United States, 75230
Research Site
Houston, Texas, United States, 77030
United States, Virginia
Research Site
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
AstraZeneca
Investigators
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Study Chair: Melissa Johnson, M.D. Tennessee Oncology
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03421353    
Other Study ID Numbers: D5660C00016
REFMAL 558 ( Other Identifier: Sarah Cannon Development Innovations, LLC )
First Posted: February 5, 2018    Key Record Dates
Last Update Posted: October 20, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
AZD9150
Durvalumab
Advanced solid tumours
Additional relevant MeSH terms:
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Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Paclitaxel
Carboplatin
Durvalumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological