Clinical Trials /

First Time in Human Study of AZD8701 With or Without Durvalumab in Participants With Advanced Solid Tumours

NCT04504669

Description:

The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of AZD8701 Alone and in Combination with Durvalumab (MEDI4736) in Adult Subjects with Select Advanced Solid Tumors

Related Conditions:
  • Breast Carcinoma
  • Cervical Carcinoma
  • Clear Cell Renal Cell Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First Time in Human Study of AZD8701 With or Without Durvalumab in Participants With Advanced Solid Tumours
  • Official Title: A Phase I First-in-Human Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD8701 Administered Intravenously as Monotherapy and in Combination With Durvaluamb (MEDI4736) in Participants With Advanced Solid Tumours.

Clinical Trial IDs

  • ORG STUDY ID: D9950C00001
  • SECONDARY ID: 2019-004539-22
  • NCT ID: NCT04504669

Conditions

  • Clear Cell Renal Cell Cancer
  • Non-Small-Cell Lung Cancer
  • Triple Negative Breast Neoplasms
  • Squamous Cell Cancer of Head and Neck
  • Small Cell Lung Cancer
  • Gastric Cancer
  • Melanoma
  • Cervical Cancer
  • Advanced Solid Tumours

Interventions

DrugSynonymsArms
AZD8701Combination Therapy
DurvalumabMEDI4736Combination Therapy

Purpose

The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of AZD8701 Alone and in Combination with Durvalumab (MEDI4736) in Adult Subjects with Select Advanced Solid Tumors

Detailed Description

      This is a Phase I, First in Human, multicentre, open-label, multiple arm study with dose
      escalations and expansions at selected doses. Dose-escalation will occur with AZD8701 in
      monotherapy (Part 1) and in combination with durvalumab (Part 3) in selected participants
      with HNSCC, TNBC, NSCLC, ccRCC, gastric cancer, melanoma, cervical cancer, small-cell lung
      cancer and/or participants with solid tumours who have demonstrated a response to prior
      PD-(L)1 treatment.

      Disease specific expansions will occur with a selected dose AZD8701 in participants with
      NSCLC (Part 2) and with a selected dose of AZD8701 and durvalumab in participants with TNBC
      and clear cell RCC (Part 4).
    

Trial Arms

NameTypeDescriptionInterventions
MonotherapyExperimentalParticipants will receive AZD8701 intravenously, on Day 1, 3, 5 and 8 and then weekly for a maximum of 2 years.
  • AZD8701
Combination TherapyExperimentalParticipants will receive AZD8701 (intravenously, on Day 1, 3, 5 and 8 and then weekly) and durvalumab (MEDI4736) intravenously monthly for a maximum of 2 years.
  • AZD8701
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

        The study is comprised of 2 main parts Monotherapy (AZD8701) and Combined Therapy (AZD8701
        and Durvalumab).

        Inclusion criteria Dose escalation stages:

          -  Histological or cytological confirmation of a solid, malignant tumour including HNSCC,
             TNBC, NSCLC, ccRCC, gastric cancer, melanoma, cervical cancer, SCLC, and/or
             participants with other solid tumours who have demonstrated a response to prior
             anti-PD-(L)1 treatment

          -  Participant with progressive disease that is refractory to standard therapies or for
             which no standard therapies exist and a clinical trial is the best option for next
             treatment based on prior response and/or tolerability to standard of care

        Inclusion Criteria Dose Expansions:

        Non Small Lung Cancer Participants who have received prior PD(L)1 treatment. Clear Cell
        Renal Cancer Participants who have not received prior PD(L)1 treatment.

        Triple negative Breast Cancer participants who have who have not received prior PD(L)1
        treatment.

        General inclusion criteria:

          -  Must be 18 year old at the time of screening

          -  Body weight > 35 kg

          -  Male and Female participants of childbearing potential must use effective methods of
             contraception

          -  Capable of giving signed informed consent

          -  ECOG performance status of 0 to 1

          -  A serum albumin > 35g/L

          -  Life expectancy of > 12 weeks

          -  At least 1 lesion, that qualifies as a RECIST 1.1 target lesion at baseline. Tumour
             assessment by CT scan or MRI must be performed within 28 days prior to treatment.

          -  Participants must provide a new or previous tumour sample

          -  Adequate organ system functions

        Exclusion Criteria:

          -  A condition that, in the opinion of the Investigator, would interfere with evaluation
             of the study intervention or interpretation of participant safety or study results

          -  History of allogeneic organ transplantation.

          -  Active or prior documented autoimmune or inflammatory disorders Uncontrolled
             intercurrent illness

          -  Significant cardiac disease

          -  History of another primary malignancy except for

               1. Malignancy treated with curative intent and with no known active disease ≥ 5
                  years

               2. non-melanoma skin cancer

               3. Adequately treated carcinoma in situ without evidence of disease.

          -  Any major unresolved toxicity from previous anticancer therapy

          -  Known allergy or hypersensitivity to any of the study interventions or any of the
             study intervention excipients.

        Prior/Concomitant Therapy

          -  Receipt of the last dose of anticancer therapy within 5 half-lives or ≤ 21 days prior
             to the first dose of study

          -  Prior treatment with potential Treg depletion therapies including agents targeting
             CTLA-4 for 90 days prior to enrolment on study.

          -  Participants who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4:

               1. Must not have experienced a toxicity that led to permanent discontinuation of
                  prior immunotherapy.

               2. All AEs while receiving prior immunotherapy must have completely resolved or
                  resolved to baseline

               3. Must not have experienced a ≥ Grade 3 imAE or a neurologic or ocular imAE of any
                  grade while receiving prior immunotherapy.

               4. Must not have required the use of additional immunosuppression other than
                  corticosteroids for the management of an AE

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of study drug. b. The following are exceptions to this criterion:

               1. Intranasal, inhaled, topical steroids, or local steroid injections (eg,
                  intra-articular injection).

               2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
                  prednisone or its equivalent

               3. Steroids as premedication for hypersensitivity reactions (eg, CT scan
                  premedication)

          -  Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy
             for cancer treatment

          -  Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
             radiation within 4 weeks of the first dose of study intervention.

          -  Major surgical procedure within 28 days prior to the first dose

          -  Participants receiving anticoagulation treatment for venous or arterial indications

          -  Participation in another clinical study with study intervention administered in the
             last 30 days

          -  Female participants who are pregnant or breastfeeding or male and female participants
             of reproductive potential who are not willing to employ effective birth control
      
Maximum Eligible Age:101 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of AEs and SAEs
Time Frame:From screening until 105 days after last dose of study treatment
Safety Issue:
Description:Determined according to Incidence and treatment related AEs and SAEs

Secondary Outcome Measures

Measure:Progression-free survival according to RECIST 1.1 by investigator assessment
Time Frame:every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Safety Issue:
Description:Time from start of study treatment to the date of objective disease progression or death (by any cause in the absence of progression)
Measure:Duration of Response according to RECIST 1.1 by investigator assessment
Time Frame:every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Safety Issue:
Description:Time from first documented response (that is subsequently confirmed) to the date of objective disease progression or death (by any cause in the absence of progression)
Measure:Disease Control Rate at 16 weeks according to RECIST 1.1 by investigator assessment
Time Frame:Every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Safety Issue:
Description:The proportion of subjects with a best response of CR or PR in first 16 weeks or SD for at least 16 weeks
Measure:Time to Response according to RECIST 1.1 by investigator assessment
Time Frame:Every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Safety Issue:
Description:Time from the start of study treatment until the date of first documented response (which is subsequently confirmed)
Measure:Best percentage change in tumour size according to RECIST 1.1 by investigator assessment
Time Frame:Every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death, start of subsequent anti-cancer therapy or end of study (for max 42 months)
Safety Issue:
Description:Best percentage change from baseline in sum of the diameters of target lesions
Measure:Overall Survival at 18 months
Time Frame:From start of treatment to earlier of death or end of study (for max 42 months)
Safety Issue:
Description:Time from start of treatment until death from any cause.
Measure:Plasma AZD8701 and associated PK parameters when administered as monotherapy and in combination with Durvalumab
Time Frame:From around 2 hours before start of first AZD8701 infusion until 105 days after last dose
Safety Issue:
Description:Data following the single and multiple-dose parts of the study will be analysed through NCA to determine Cmax
Measure:Plasma and urine concentrations of AZD8701 and associated PK parameters when administered as monotherapy and in combination with Durvalumab
Time Frame:From around 2 hours before start of first AZD8701 infusion until 105 days after last dose
Safety Issue:
Description:Data following the single and multiple-dose parts of the study will be analysed through NCA to determine tmax
Measure:Plasma and urine concentrations of AZD8701 and associated PK parameters when administered as monotherapy and in combination with Durvalumab
Time Frame:From around 2 hours before start of first AZD8701 infusion until 105 days after last dose
Safety Issue:
Description:Data following the single and multiple-dose parts of the study will be analysed through NCA to determine AUC
Measure:Urine concentrations of AZD8701 to assess renal clearance when administered as monotherapy and in combination with Durvalumab
Time Frame:From around 2 hours before start of first AZD8701 infusion to day 50
Safety Issue:
Description:Urine samples will be collected to assess urine concentrations of AZD8701 at a series of timepoints to derive renal clearance
Measure:Serum concentrations of Durvalumab and associated PK parameters when administered in combination with AZD8701
Time Frame:From before start of first infusion of Durvalumab until 105 days after last dose
Safety Issue:
Description:The following and other PK parameters may be reported as data allow: Cmax on Cycle 4 Day 1 (end of infusion concentration) and Cmin on Cycle 4 Day 1 (pre-dose concentration).
Measure:Change in FOXP3 mRNA expression
Time Frame:From day 1 to day 29
Safety Issue:
Description:Percentage change in FOXP3 mRNA expression from pre-treatment (baseline) to post treatment

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Solid Tumours
  • Durvalumab
  • MEDI4736
  • AZD8701
  • Non Small cell Lung cancer
  • ccRenal Cancer
  • TNBC
  • first time in human
  • PD-L1
  • T regulatory cells
  • FOXP3

Last Updated

August 5, 2020