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 | Completed Phase 1 FDA Drug

• 4 other identifiers: D5660C00016REFMAL 5582644762017-004925-34
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 6

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)

Conditions

Advanced Solid Tumours

Keywords

AZD9150; Durvalumab; Advanced solid tumours

Outcome Measures

Primary Outcomes (3)

• Part A: Maximum Tolerated Dose (MTD) in subjects receiving AZD9150 plus durvalumab and AZD9150 plus durvalumab plus 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.

  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.

• 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.

  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.

  Blood samples for the PK analysis of AZD9150 will be collected at prespecified intervals during Weeks 0, 1, 5, 6, and 9.

• Part D: Minimum plasma concentration at steady state [Ctrough (ss)] of AZD9150 administered once per week in combination with durvalumab.

  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.

  Blood samples for the PK analysis of AZD9150 will be collected at prespecified intervals during Weeks 0, 1, 5, 6, and 9.

Secondary Outcomes (30)

• Part A: Disease Control Rate (DCR)

  12 weeks

• Part A: Duration of Overall Response (DoR)

  Throughout the study (approximately 6 months).

• Part A: Progression-Free Survival (PFS)

  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

• Part A: AZD9150 anti-drug antibody titres

  Blood samples for AZD9150 anti-drug antibodies (ADAs) will be collected predose on prespecified dosing days up to 9 weeks.

• Part A: Durvalumab anti-drug antibody titres

  Blood samples for durvalumab anti-drug antibodies (ADAs) will be collected predose on prespecified dosing days up to 13 weeks.

Study Arms (7)

Arm A1

EXPERIMENTAL

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; Drug: Durvalumab

Arm A2

EXPERIMENTAL

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; Drug: Durvalumab; Drug: Cisplatin; Drug: 5-Flourouracil

Arm A3

EXPERIMENTAL

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; Drug: Durvalumab; Drug: Cisplatin; Drug: 5-Flourouracil

Arm A4

EXPERIMENTAL

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; Drug: Durvalumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Gemcitabine

Arm A5

EXPERIMENTAL

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; Drug: Durvalumab; Drug: Carboplatin; Drug: Nab-paclitaxel

Arm D: AZD9150 SC

EXPERIMENTAL

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; Drug: Durvalumab

Arm D: AZD9150 IV

EXPERIMENTAL

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; Drug: Durvalumab

Interventions

AZD9150 DRUG

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.

Arm A1; Arm A2; Arm A3; Arm A4; Arm A5; Arm D: AZD9150 IV; Arm D: AZD9150 SC

Durvalumab DRUG

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.

Also known as: MEDI4736

Arm A1; Arm A2; Arm A3; Arm A4; Arm A5; Arm D: AZD9150 IV; Arm D: AZD9150 SC

Cisplatin DRUG

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

Arm A2; Arm A3; Arm A4

5-Flourouracil DRUG

5-flourouracil will be continuously infused over Days 1 to 4 every three weeks for up to 18 weeks.

Also known as: 5-FU

Arm A2; Arm A3

Carboplatin DRUG

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.

Arm A4; Arm A5

Gemcitabine DRUG

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

Arm A4

Nab-paclitaxel DRUG

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

Arm A5

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• ≥ 18 years of age.
• An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Minimum life expectancy of 12 weeks
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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).
• Previous enrolment in the present study.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (6)

Research Site

Lafayette, Indiana, 47905, United States

Location

Research Site

Oklahoma City, Oklahoma, 73104, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Dallas, Texas, 75230, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Fairfax, Virginia, 22031, United States

Location

Related Links

• CSR\_synopsis

MeSH Terms

Interventions

danvatirsen; durvalumab; Cisplatin; Fluorouracil; Carboplatin; Gemcitabine; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides

Study Officials

• Melissa Johnson, M.D.

  Tennessee Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: February 5, 2018
• Study Start: February 7, 2018
• Primary Completion: January 17, 2020
• Study Completion: March 28, 2024
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA 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 anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (6)