Clinical Trials /

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

NCT03421353

Description:

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).

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: D5660C00016
  • SECONDARY ID: REFMAL 558
  • NCT ID: NCT03421353

Conditions

  • Advanced Solid Tumours

Interventions

DrugSynonymsArms
AZD9150Arm A1
DurvalumabMEDI4736Arm A1
CisplatinArm A2
5-Flourouracil5-FUArm A2
CarboplatinArm A4
GemcitabineArm A4
Nab-paclitaxelArm A5

Purpose

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).

Detailed Description

      This international, multicenter study was originally intended to be conducted in four parts,
      designated as Parts A, B, C, and D. The protocol was amended in December 2018 to remove Parts
      B and C. Parts B and C were intended to evaluate patients with locally advanced or metastatic
      Stage IV NSCLC; however, these parts of the study will not be conducted.

      Part A of this study will evaluate the safety and tolerability of durvalumab and AZD9150 with
      and without selected chemotherapy regimens, and will include patients with advanced solid
      malignancies that are refractory to standard therapy or for whom no standard of care (SOC)
      regimen currently exists.

      Part D will compare the relative bioavailability of the AZD9150 subcutaneous (SC) versus
      intravenous (IV) formulations in patients with confirmed solid malignancies that are
      refractory to standard therapy or for whom no SOC regimen currently exists. Approximately 50
      to 62 PK-evaluable patients will be enrolled in Part D. Patients will be randomly assigned to
      either SC or IV AZD9150. For Part D, the PK Analysis set will include all patients who
      receive both study drugs (both AZD9150 and durvalumab) and have at least one PK sample
      collection.

      A complementary anti-tumour strategy will be used in this study with 2 immuno-therapeutics
      applied to restore effective anti-tumour immunity at 2 distinct stages: promoting the
      effector function of T-cell responses with an anti-PD-L1 mAb, durvalumab, while hindering
      immune escape in the tumour bed with AZD9150. In addition, chemotherapy will be added to this
      combination to investigate possible future enhancement of response. In preclinical models,
      conventional platinum-based chemotherapy has been shown to induce T-cell activation through
      the release of tumour-specific antigens during cancer cell death. The elimination of
      persistent tolerogenic tumour antigen environment via chemotherapy-induced debulking may also
      play a role in generating an effective immune response. In this setting, immunotherapy has
      the potential to mount an ongoing and dynamic immune response that can kill tumour cells for
      an extended time.

      Part A of the study will be conducted in five arms, designated Arms A1, A2, A3, A4, and A5.
      The primary objective of Part A is to assess the safety and tolerability, and determining the
      maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of AZD9150 plus durvalumab in
      patients with advanced solid malignancies. In addition, another primary objective is to
      assess the safety and tolerability, and determine the maximum tolerated dose/recommended
      phase 2 dose (MTD/RP2D) of AZD9150 plus durvalumab in combination with standard chemotherapy
      regimens in patients with advanced solid malignancies. Approximately 30 to 78 DLT-evaluable
      patients will be enrolled in Part A.

      In Arm A1, patients will receive AZD9150 by (IV) infusion Q2W + durvalumab by IV infusion
      Q4W. Chemotherapy will not be given in Arm A1.

      Arm A2 patients will receive AZD9150 IV QW + durvalumab IV Q3W, cisplatin by slow IV infusion
      over 1-4 hours on Day 1 + 5-fluorouracil (5FU) by continuous IV infusion over 96 hours (Days
      1 through 4, repeated every 3 weeks for up to 18 weeks). In Arm A2 there will be a AZD9150 +
      chemotherapy lead-in period prior to durvalumab dosing. The last chemotherapy dose will be
      given in Week 15. After discontinuation of chemotherapy the regimen will include AZD9150 IV
      QW + durvalumab IV Q4W. Administration of durvalumab will continue Q3W through Week 19, at
      which time the schedule will switch to Q4W (e.g., Week 23, 27, 31, etc.).

      Depending on the results from Arm A2, Arm A3 may not be conducted. If the Safety Review
      Committee (SRC) decides to open Arm A3, the SRC will determine the starting dose. Patients
      will be administered one of the following 4 chemotherapy regimens in combination with AZD9150
      and durvalumab appropriate for their tumour type:

        -  In Arm A3, patients will receive cisplatin by slow IV infusion over 1-4 hours on Day 1 +
           5FU by continuous IV infusion over 96 hours (Days 1 through 4, repeated every 3 weeks
           for up to 18 weeks).

        -  In Arm A4, patients will receive gemcitabine by IV infusion over 30 minutes on Days 1
           and 8 every 3 weeks for 12 to 18 weeks, plus either:

             -  for cisplatin-eligible patients: cisplatin IV over 30 minutes on Day 1 (every 3
                weeks for up to 12 to 18 weeks); or

             -  for cisplatin-ineligible patients: carboplatin IV over 30 to 60 minutes on Day 1
                (every 3 weeks for up to 12 to 18 weeks).

        -  In Arm A5, patients will receive carboplatin at AUC 5 IV over 30 to 60 minutes on Day 1
           + nab-paclitaxel IV over 30 to 40 minutes on Days 1, 8, and 15 (every 3 weeks for up to
           12 to 18 weeks).

      There will be an AZD9150 7-day lead-in period (termed Week 0) in all arms in all parts of the
      study. AZD9150 will be given IV on Days 1,3, and 5 of the lead-in week. When chemotherapy is
      administered, the dosing of chemotherapy will also commence during the lead-in period with
      AZD9150. In Arm A2 of Part A, dosing with AZD9150 IV, durvalumab, and chemotherapy will
      commence on Day 1 of Week 0. In Part D, dosing with AZD9150 IV or SC will commence on Day 1
      of Week 0.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A1ExperimentalPatients 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.
  • AZD9150
  • Durvalumab
Arm A2ExperimentalPatients 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.
  • AZD9150
  • Durvalumab
  • Cisplatin
  • 5-Flourouracil
Arm A3ExperimentalDepending 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.
  • AZD9150
  • Durvalumab
  • Cisplatin
  • 5-Flourouracil
Arm A4ExperimentalPatients 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.
  • AZD9150
  • Durvalumab
  • Cisplatin
  • Carboplatin
  • Gemcitabine
Arm A5ExperimentalPatients 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.
  • AZD9150
  • Durvalumab
  • Carboplatin
  • Nab-paclitaxel
Arm D: AZD9150 SCExperimentalPart 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.
  • AZD9150
  • Durvalumab
Arm D: AZD9150 IVExperimentalPart 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.
  • AZD9150
  • Durvalumab

Eligibility 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.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Part A: Disease Control Rate (DCR)
Time Frame:12 weeks
Safety Issue:
Description: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).
Measure:Part A: Duration of Overall Response (DoR)
Time Frame:Throughout the study (approximately 6 months).
Safety Issue:
Description: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).
Measure: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
Safety Issue:
Description: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).
Measure: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.
Safety Issue:
Description:Unwanted immunogenicity in the form of anti-drug-antibodies (ADAs) will be assessed.
Measure: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.
Safety Issue:
Description:Unwanted immunogenicity in the form of anti-drug-antibodies (ADAs) will be assessed.
Measure:Part A: Baseline tumour PD-L1 expression
Time Frame:Pre-dose
Safety Issue:
Description: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.
Measure:Part A: STAT3 protein in tumour biopsies
Time Frame:Predose and 3 weeks after start of treatment
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description:The peak plasma concentration (Cmax,ss) of AZD9150 at steady state after multiple doses in combination with durvalumab Q4W will be determined.
Measure: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.
Safety Issue:
Description:The trough plasma concentration (Ctrough,ss) of AZD9150 at steady state after multiple doses in combination with durvalumab Q4W will be determined.
Measure: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)
Safety Issue:
Description:The area under the plasma concentration versus time curve (AUC) of AZD9150 after single-dose given in combination with durvalumab Q4W will be determined.
Measure: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)
Safety Issue:
Description: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.
Measure:Part D: Injection site tolerability for patients receiving subcutaneous injections.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description:Pain, tenderness, redness, and other symptoms will be assessed for subcutaneous injection of AZD9150.
Measure:Part D: The incidence of adverse events (AEs) in subjects receiving AZD9150.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description:The incidence of adverse events will be determined for each treatment arm in Part D of the study.
Measure:Part D: The incidence of serious adverse events (SAEs) in subjects receiving AZD9150.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description:The incidence of serious adverse events will be determined for each treatment arm in Part D of the study.
Measure:Part D: Peak plasma concentration (Cmax) of AZD9150 after single-dose.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure:Part D: Time to peak plasma concentration (tmax) of AZD9150 after single-dose.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure:Part D: The systemic clearance (CL) of AZD9150 after single-dose.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description: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.
Measure:Part D: The systemic clearance [CL(ss)] of AZD9150 after multiple doses.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description: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.
Measure:Part D: The apparent systemic clearance (CL/F) of AZD9150 after single-dose.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description: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.
Measure:Part D: The volume of distribution (Vz/F) of AZD9150 after single-dose.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description: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.
Measure:Part D: The mean residence time (MRT) of AZD9150 after single-dose.
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description: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.
Measure:Part D: The elimination half-life (t1/2) of AZD9150 after single-dose
Time Frame:Through study completion (an average of 6 months)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • AZD9150
  • Durvalumab
  • Advanced solid tumours

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