Clinical Trials /

Javelin BRCA/ATM: Avelumab Plus Talazoparib in Patients With BRCA or ATM Mutant Solid Tumors

NCT03565991

Description:

Avelumab in combination with talazoparib will be investigated in patients with locally advanced or metastatic solid tumors with a BRCA or ATM defect.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Javelin BRCA/ATM: Avelumab Plus Talazoparib in Patients With BRCA or ATM Mutant Solid Tumors
  • Official Title: A PHASE 2 STUDY TO EVALUATE SAFETY AND ANTI-TUMOR ACTIVITY OF AVELUMAB IN COMBINATION WITH TALAZOPARIB IN PATIENTS WITH BRCA OR ATM MUTANT TUMORS

Clinical Trial IDs

  • ORG STUDY ID: B9991032
  • SECONDARY ID: 2018-000345-39
  • NCT ID: NCT03565991

Conditions

  • Locally Advanced or Metastatic Solid Tumors
  • Genes, BRCA 1

Interventions

DrugSynonymsArms
AvelumabBavencioCombination of avelumab and talazoparib
TalazoparibMDV3800, BMN 673Combination of avelumab and talazoparib

Purpose

Avelumab in combination with talazoparib will be investigated in patients with locally advanced or metastatic solid tumors with a BRCA or ATM defect.

Detailed Description

      Avelumab is a human immunoglobulin (Ig)G1 monoclonal antibody (mAb) directed against
      programmed death ligand 1 (PD-L1). Avelumab selectively binds to PD-L1 and competitively
      blocks its interaction with programmed death receptor 1 (PD-1), thereby interfering with this
      key immune checkpoint inhibition pathway. Avelumab is currently being investigated as single
      agent and in combination with other anti cancer therapies in patients with locally advanced
      or metastatic solid tumors and various hematological malignancies.

      Talazoparib is a potent, orally bioavailable poly (adenosine diphosphate [ADP] ribose)
      polymerase (PARP) inhibitor, which is cytotoxic to human cancer cell lines harboring gene
      mutations that compromise deoxyribonucleic acid (DNA) repair, an effect referred to as
      synthetic lethality, and by trapping PARP protein on DNA thereby preventing DNA repair,
      replication, and transcription.

      Avelumab in combination with talazoparib will be investigated in patients with locally
      advanced (primary or recurrent) or metastatic solid tumors with a BReast CAncer
      susceptibility gene (BRCA)1, or BRCA2, or ataxia telangiectasia mutated (ATM) gene defect.
    

Trial Arms

NameTypeDescriptionInterventions
Combination of avelumab and talazoparibExperimentalSingle arm open label
  • Avelumab
  • Talazoparib

Eligibility Criteria

        Inclusion Criteria:

          -  BRCA1, BRCA2 and/or ATM gene defect.

          -  Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid
             tumors that are not amenable for treatment with curative intent

          -  Availability a tumor tissue sample from a diagnostic biopsy/surgery or a metastatic
             tumor biopsy.

          -  Progressive disease at study enrollment.

          -  Minimum age 18 years (in Japan, minimum age 20 years).

          -  ECOG performance status 0 or 1.

          -  Adequate bone marrow, renal and liver function.

          -  For childbearing female patients, negative serum or urine pregnancy test at screening

          -  Signed and dated informed consent document.

        Exclusion Criteria:

          -  Prior anti-cancer therapy or radiation therapy within 2 weeks prior to enrolment.
             Palliative radiotherapy to metastatic lesion(s) permitted providing that it has been
             completed at least 2 days prior to enrolment and no significant toxicity are expected.

          -  Major surgery within 4 weeks prior to study enrollment.

          -  Current use of immunosuppressive medication at the time of study enrollment.

          -  Known prior severe hypersensitivity to investigational products or any component in
             their formulations

          -  Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis,
             pulmonary fibrosis.

          -  Active or prior autoimmune disease that might deteriorate when receiving an
             immunostimulatory agent.

          -  Prior organ transplantation including allogenic stem-cell transplantation.

          -  Administration of live attenuated vaccines within 4 weeks of study enrollment.

          -  Diagnosis of myelodysplastic syndrome.

          -  Known symptomatic brain metastases requiring steroids.

          -  Persisting toxicity related to prior therapy Grade >1.

          -  Known history of HIV or AIDS.

          -  Positive HBV or HCV test indicating acute or chronic infection.

          -  Active infection requiring systemic therapy.

          -  Clinically significant (active) cardiovascular disease: cerebral vascular
             accident/stroke or myocardial infarction within 6 months prior to study enrollment;
             unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring
             medication.

          -  Diagnosis of any other malignancy within 2 years prior to study enrollment, except for
             adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of
             the breast, bladder, or cervix, or low-grade prostate cancer or other early-stage
             low-risk cancers.

          -  Pregnant or breastfeeding female patients; female or male patients who are able to
             have children who are unable or unwilling to use contraception as outlined in the
             protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed Objective Response (OR)
Time Frame:From date of first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to approximately 24 months
Safety Issue:
Description:Confirmed OR in patients with locally advanced or metastatic solid tumors with BRCA 1/2 or ATM defect, as assessed by Blinded Independent Central Review using RECIST v1.1 and, in patients with mCRPC, RECIST v1.1. and PCWG3.

Secondary Outcome Measures

Measure:Confirmed OR as assessed by the investigator
Time Frame:From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to approximately 24 months
Safety Issue:
Description:Confirmed OR as assessed by the investigator, using RECIST v1.1 and, in patients with mCRPC, RECIST v1.1 and PCWG3.
Measure:Time to tumor response (TTR)
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:TTR is defined for patients with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response.
Measure:Duration of response (DR)
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:DR is defined for patients with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
Measure:Progression free survival (PFS)
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:PFS is defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurs first.
Measure:Overall survival (OS)
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:OS is defined as the time from the first dose of study treatment to the date of death.
Measure:Time to prostate-specific antigen (PSA) progression for mCRPC patients
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:Time to PSA progression is defined as the time from the first dose to the date that a greater than or equal to 25% increase in PSA from baseline.
Measure:CA-125 response for ovarian cancer patients
Time Frame:Baseline and Day 1 of each Cycle (1 cycle is 28 days)
Safety Issue:
Description:CA-125 response is defined as at least a 50% reduction in CA-125 levels from baseline.
Measure:Prostate specific antigen (PSA) response
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:PSA response is defined as at least a 50% reduction in PSA levels from baseline
Measure:Circulating Tumor Cells (CTC) count conversion for mCRPC patients
Time Frame:Day 1 Cycles 1-4
Safety Issue:
Description:CTC conversion for mCRPC patients
Measure:Biomarker PD-L1
Time Frame:Baseline
Safety Issue:
Description:PD-L1 expression level in baseline tumor tissue.
Measure:Presence of defects in a panel of key oncogenes
Time Frame:Baseline.
Safety Issue:
Description:Presence of defects in a panel of key oncogenes.
Measure:Plasma concentrations Ctrough talazoparib
Time Frame:Day 1, Day 15 Cycle 3
Safety Issue:
Description:Pharmacokinetic parameter for talazoparib.
Measure:Plasma concentrations post-dose talazoparib
Time Frame:Day 1, Day 15 Cycle 3
Safety Issue:
Description:Pharmacokinetic parameter for talazoparib.
Measure:Serum concentrations Ctrough avelumab
Time Frame:Day 1 Cycles 1, 3, 6, 12, 18, 24 and Day 15 Cycle 1
Safety Issue:
Description:Pharmacokinetic parameter for avelumab.
Measure:Serum concentrations Cmax avelumab
Time Frame:Day 1 Cycles 1, 3, 6, 12, 18, 24 and Day 15 Cycle 1
Safety Issue:
Description:Pharmacokinetic parameter for avelumab.
Measure:Anti-drug antibody (ADA) levels of avelumab
Time Frame:Day 1 Cycles 1, 3, 6, 12, 18, 24 and Day 15 Cycle 1
Safety Issue:
Description:Immunogenicity assessment of avelumab.
Measure:Neurtralizing antibodies (Nab) levels against avelumab
Time Frame:Day 1 Cycles 1, 3, 6, 12, 18, 24 and Day 15 Cycle 1
Safety Issue:
Description:Immunogenicity assessment of avelumab.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • BRCA, ATM

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