Clinical Trials /

A Phase I/II Study of MEDI4736 in Combination With Olaparib in Patients With Advanced Solid Tumors.

NCT02734004

Description:

The purpose of this study is to look at the effectiveness, safety, and antitumor activity of study drugs MEDI4736 in combination with olaparib (modules 1, 2, 3, 4, 5 and 7, 8 and 9) and MEDI4736 in combination with olaparib and bevacizumab (module 6 and 10). It will also examine what happens to the study drugs in the body and investigate how well the combination between MEDI4736, olaparib and bevacizumab is tolerated.

Related Conditions:
  • Breast Carcinoma
  • Gastric Carcinoma
  • Ovarian Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase I/II Study of MEDI4736 in Combination With Olaparib in Patients With Advanced Solid Tumors.
  • Official Title: A Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination With Olaparib (PARP Inhibitor) in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: D081KC00001
  • SECONDARY ID: 2015-004005-16
  • NCT ID: NCT02734004

Conditions

  • Ovarian
  • Breast
  • SCLC
  • Gastric Cancers

Interventions

DrugSynonymsArms
OlaparibArm 1: Olaparib / MEDI4736
MEDI4736Arm 1: Olaparib / MEDI4736

Purpose

The purpose of this study is to look at the effectiveness, safety, and antitumor activity of study drugs MEDI4736 in combination with olaparib. It will also examine what happens to the study drugs in the body and investigate how well the combination between MEDI4736 and olaparib is tolerated.

Detailed Description

      This is a phase I/II open-label, multicenter study to evaluate the safety, tolerability,
      pharmacokinetics (PK) and antitumor activity of MEDI4736 in combination with olaparib in
      patients with advanced solid tumors, selected based on a rationale for response to olaparib.

      Patients will be poly (adenosine diphosphate-ribose) polymerase (PARP)-inhibitor and
      immunotherapy (IMT)-naïve (defined as no prior exposure to PARP inhibitors or IMT, including,
      but not limited to, other anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4],
      anti-programmed cell death 1 [PD-1], anti-programmed death-ligand 1 [PD-L1] monoclonal
      antibodies, or any other antibody or drug specifically targeting T-cell co-stimulation or
      checkpoint pathways).

      Initially, patients will be enrolled concurrently into 4 exploratory cohorts, which will
      include patients with relapsed SCLC, gBRCAm metastatic HER2-negative breast cancer, gBRCAm
      platinum-sensitive relapsed ovarian cancer, and gastric cancer. Additional tumor types may be
      added at a later date based on emerging data. The results from this study will form
      decision-making for future studies.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1: Olaparib / MEDI4736ExperimentalOlaparib PO 300mg BID starting on week 1 day 1 / MEDI4736 IV 1.5g every 4 weeks starting on week 5 day 1
  • Olaparib
  • MEDI4736

Eligibility Criteria

        Inclusion criteria:

          -  Patients must have histologically or cytologically confirmed progressive advanced or
             metastatic solid tumor of one of the following:

               -  gBRCAm ovarian cancer

               -  gBRCAm HER2-negative metastatic breast cancer

               -  Platinum sensitive relapsed small cell lung cancer

               -  Metastatic or relapsed Gastric cancer (adenocarcinoma)

          -  At least one measurable lesion that can be accurately assessed at baseline by computed
             tomography (CT) (or magnetic resonance imaging [MRI] suitable for assessment as per
             RECIST 1.1. The baseline scan must be obtained within 28 days prior to the first dose
             of olaparib.

          -  Male or female patients, age ≥18 years (≥19 years for South Korea)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Life expectancy ≥12 weeks

          -  Adequate organ and marrow function

          -  Ability to swallow oral medications (capsules and tablets) without chewing, breaking,
             crushing, opening or otherwise altering the product formulation. Patients should not
             have gastrointestinal illnesses that would preclude the absorption of olaparib, which
             is an oral agent. For the gastric cancer cohort, patients with a full or partial
             gastrectomy will be permitted.

          -  Ability of patient to understand and the willingness to sign a written informed
             consent document prior to any protocol related procedures, including screening
             evaluations.

          -  Female patients must either:

               -  Be of non-reproductive potential OR

               -  Have a negative serum pregnancy test within 28 days of study treatment and
                  confirmed prior to treatment on Day 1, and agree to use contraception if they or
                  their partner are of reproductive potential

        Exclusion criteria

          -  Prior chemotherapy or other systemic anticancer therapy within 4 weeks prior to start
             of olaparib treatment, 6 weeks for nitrosoureas or mitomycin. Exceptions include:
             Anti-hormonal treatment for ER positive or PR positive breast cancer is allowed until
             7 days prior to treatment with olaparib, exposure to an investigational agent within
             30 days or 5 half-lives (whichever is the longer) prior to start of olaparib treatment
             is not allowed, prior receipt of biologics targeting T cell co-regulatory proteins
             and/or immune checkpoints is not allowed. Examples include MEDI4736 or other PD1 or
             PD-L1 or PD-L2 inhibitors or anti-CTLA4 therapy, previous treatment with a PARP
             inhibitor, is not allowed.

          -  Radiation therapy within 4 weeks prior to start of olaparib treatment (includes
             radiation targeting bone metastases) or radionuclide treatment within 6 weeks of
             treatment start.

          -  Current dependency on total parenteral nutrition or IV fluid hydration.

          -  Concomitant use of known strong cytochrome P450 (CYP) 3A (CYP3A) inhibitors or
             moderate CYP3A inhibitors. Concomitant use of known strong or moderate CYP3A inducers.

          -  Concomitant therapy with any other anticancer therapy or chronic use of systemic
             corticosteroids.

          -  Previous allogenic bone marrow transplant or double umbilical cord blood
             transplantation

          -  Whole blood transfusions in the last 120 days

          -  Known brain metastases or spinal cord compression

          -  Patients being considered at poor medical risk due to a serious, uncontrolled medical
             disorder or non-malignant systemic disease.

          -  Any psychiatric disorder that prohibits obtaining informed consent

          -  Major surgery or significant traumatic injury within 2 weeks of run-in

          -  Immunocompromised patients

          -  QTc prolongation >470 msec or other significant ECG abnormality noted within 14 days
             of treatment

          -  Pregnant and breastfeeding women are excluded.

          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site)

          -  Previous enrolment in the present study

          -  Participation in a clinical study within 28 days or 5 half-lives of the drug,
             whichever is longer.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] based on modified RECIST 1.1
Time Frame:At 12 weeks, compared to Baseline
Safety Issue:
Description:Assessments will be performed using CT/MRI assessments of the chest, abdomen, and pelvis

Secondary Outcome Measures

Measure:PD-L1 expression in serum samples
Time Frame:Each cycle = 28 days in combination of treatment. Day 1 of cycle 1; Day 15 of cycle 1; Day 1 of cycle 3; Day 1 of cycle 5; Day 1 of cycle 7; 3 month Follow-up visit
Safety Issue:
Description:Samples will be measured for the presence of sPD-L1
Measure:Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] based on modified RECIST 1.1
Time Frame:At 28 weeks, compared to Baseline
Safety Issue:
Description:Assessments will be performed using CT/MRI assessments of the chest, abdomen, and pelvis
Measure:Time to study treatment discontinuation (TDT)
Time Frame:From Cycle 1, Day 1 up to 52 weeks.
Safety Issue:
Description:Time of study treatment discontinuation or death
Measure:Overall Survival (OS)
Time Frame:From Cycle 1, Day 1 until death or up to 52 weeks.
Safety Issue:
Description:Time from start of Olaparib treatment until death due to any cause
Measure:Percentage change from baseline in tumor size
Time Frame:At 12 weeks and 28 weeks compared to Baseline
Safety Issue:
Description:Assessments will be performed using CT/MRI assessments of the chest, abdomen, and pelvis
Measure:Best percentage change from baseline in tumor size
Time Frame:From Baseline, at 4 weeks and every 8 weeks thereafter up to 52 weeks.
Safety Issue:
Description:Assessments will be performed using CT/MRI assessments of the chest, abdomen, and pelvis
Measure:Serum concentrations of anti-drug antibody (ADA)
Time Frame:Each cycle = 28 days in combination of treatment. Day 1 of cycle 1; Day 15 of cycle 1; Day 1 of cycle 3; Day 1 of cycle 5; Day 1 of cycle 7; 3 month Follow-up visit
Safety Issue:
Description:Samples will be measured for the presence of MEDI4736 ADAs
Measure:Olaparib pharamacokinetic sample
Time Frame:Olaparib Run-In treatment week 1 day 1; Olaparib Run-In treatment week 4 day 1; Day 15 of Cycle 1
Safety Issue:
Description:Samples will be collected for determination of Olaparib levels in plasma
Measure:MEDI4736 pharmacokinetic sample
Time Frame:Each cycle = 28 days in combination of treatment. Day 1 of cycle 1; Day 15 of cycle 1; Day 1 of cycle 3; Day 1 of cycle 5; Day 1 of cycle 7; 3 month Follow-up visit
Safety Issue:
Description:Samples will be collected for determination of MEDI4736 levels in plasma
Measure:Objective response rate (Complete response+Partial response) based on modified RECIST 1.1
Time Frame:From Baseline, at 4 weeks and every 8 weeks thereafter up to 52 weeks
Safety Issue:
Description:
Measure:Duration of response based on modified RECIST 1.1
Time Frame:From Baseline, at 4 weeks and every 8 weeks thereafter up to 52 weeks.
Safety Issue:
Description:
Measure:PFS based on modified RECIST 1.1
Time Frame:From Baseline, at 4 weeks and every 8 weeks thereafter up to 52 weeks.
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • MEDIOLA
  • Olaparib
  • MEDI4736
  • Ovarian cancer
  • Breast cancer
  • Small Cell Lung Cancer
  • Gastric Cancer
  • Phase I/II, Adults
  • PDL-1

Last Updated

October 9, 2017