Clinical Trials /

Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors

NCT03330405

Description:

Avelumab in combination with talazoparib will be investigated in patients with locally advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration resistant prostate cancer (CRPC).

Related Conditions:
  • Breast Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Prostate Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors
  • Official Title: A Phase 1b/2 Study To Evaluate Safety And Anti Tumor Activity Of Avelumab In Combination With The Poly(Adenosine Diphosphate [Adp]-Ribose) Polymerase (Parp) Inhibitor Talazoparib In Patients With Locally Advanced Or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: B9991025
  • SECONDARY ID: 2017-001509-33
  • SECONDARY ID: JAVELIN PARP MEDLEY
  • NCT ID: NCT03330405

Conditions

  • Avelumab in Combination With Talazoparib Will be Investigated in Patients With Locally Advanced (Primary or Recurrent) or Metastatic Solid Tumors

Interventions

DrugSynonymsArms
Avelumab Phase 1bMSB0010718CDose Level 0 Phase 1b
Talazoparib Phase 1bMDV3800, BMN 673Dose Level 0 Phase 1b
Avelumab Phase 2MSB0010718CA1. NSCLC Phase 2
Talazoparib Phase 2MDV3800, BMN 673A1. NSCLC Phase 2

Purpose

Avelumab in combination with talazoparib will be investigated in patients with locally advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration resistant prostate cancer (CRPC).

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, including non-small cell lung
      cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast
      cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration
      resistant prostate cancer (CRPC).
    

Trial Arms

NameTypeDescriptionInterventions
Dose Level 0 Phase 1bExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 1b
  • Talazoparib Phase 1b
Dose Level -1 Phase 1bExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 1b
  • Talazoparib Phase 1b
Dose Level -2 Phase 1bExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 1b
  • Talazoparib Phase 1b
A1. NSCLC Phase 2ExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 2
  • Talazoparib Phase 2
A2. NSCLC PD-L1+ Phase 2ExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 2
  • Talazoparib Phase 2
B1. TNBC Phase 2ExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 2
  • Talazoparib Phase 2
B2. HR+BC DDR Defect +Assay Phase 2ExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 2
  • Talazoparib Phase 2
C1. Ovarian CA Recurrent Plat-Sensitive Phase 2ExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 2
  • Talazoparib Phase 2
C2.Ovarian CA Recurrent Plat-Sensitive BRCA defect Phase 2ExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 2
  • Talazoparib Phase 2
D.Urothelial CA Phase 2ExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 2
  • Talazoparib Phase 2
E1. CRPC Phase 2ExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 2
  • Talazoparib Phase 2
E2. CRPC DDR Defect +Assay Phase 2ExperimentalDrug: Avelumab Drug: Talazoparib
  • Avelumab Phase 2
  • Talazoparib Phase 2

Eligibility Criteria

        Inclusion Criteria:

          -  Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid
             tumors that are not amenable for treatment with curative intent in adult patients
             with: NSCLC, TNBC, HR+ breast cancer, recurrent platinum sensitive ovarian cancer, UC,
             and CRPC

          -  Mandatory primary or metastatic tumor biopsy. If archival tumor tissue is available
             from a biopsy/surgery the tumor tissue may be submitted without repeating a tumor
             biopsy during the screening period.

          -  Minimum age in Japan is 20 years.

          -  ECOG performance status 0 or 1.

          -  Resolved acute effects of prior therapy

          -  Adequate bone marrow, renal, and liver function.

          -  Negative serum pregnancy test at screening.

          -  Male and female patients able to have children must agree to use 2 highly effective
             methods of contraception throughout the study and for up to 45 days for female
             patients and 105 days for male patients after the last dose.

          -  Signed and dated informed consent.

        Exclusion Criteria:

          -  Prior treatment with a PARP inhibitor.

          -  Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2,
             anti-CD137, OX 40, GITR, LAG 3, IDO, TDO,TIM 3, CTLA-4 antibody, or any other antibody
             or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
             Prior treatment with Sipuleucel-T for patients with mCRPC is allowed.

          -  Prior anti-cancer therapy within 4 weeks prior to study enrollment. Prior radiation
             therapy within 2 weeks prior to enrollment. Prior palliative radiotherapy to
             metastatic lesion(s) is permitted, provided it has been completed 2 days prior to
             study enrollment and no clinically significant toxicities are expected (eg, mucositis,
             esophagitis).

          -  Major surgery within 4 weeks prior to study enrollment.

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

          -  Known prior or suspected hypersensitivity to investigational products.

          -  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.

          -  Vaccination within 4 weeks of study enrollment and while on trial is prohibited except
             for administration of inactivated vaccines.

          -  Diagnosis of Myelodysplastic Syndrome.

          -  Patients with known brain metastases requiring steroids.

          -  Participation in other studies involving investigational drug(s) within 4 weeks prior
             to study participation and/or during study participation.

          -  Persisting toxicity related to prior therapy >Grade 1

          -  Known HIV or AIDs-related illness.

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

          -  Active infection requiring systemic therapy.

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

          -  Current or anticipated use of a strong P glycoprotein (P gp) inhibitor (eg,
             dronedarone, quinidine, ranolazine, itraconazole, ketoconazole), strong P gp inducer
             (eg, rifampin, ritonavir, tipranavir), or strong inhibitor of breast cancer resistance
             protein (BCRP) (eg, elacridar [GF120918]).

          -  Other acute or chronic medical or psychiatric conditions.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity (DLT)
Time Frame:Cycle 1 Days 1-28 (28 days from date of first dose of study treatment)
Safety Issue:
Description:Phase 1b: DLT during the DLT evaluation period (Cycle 1)

Secondary Outcome Measures

Measure:Serum concentrations of avelumab
Time Frame:Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1
Safety Issue:
Description:Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
Measure:Anti drug antibody (ADA) levels of avelumab
Time Frame:Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1
Safety Issue:
Description:Immunogenicity assessment of avelumab
Measure:OR
Time Frame:From the start of treatment until disease progression/recurrence up to approximately 24 months
Safety Issue:
Description:Phase 1b: Confirmed OR, as assessed by the Investigator using RECIST v1.1 in patients with locally advanced or metastatic solid tumors and RECIST v1.1 and PCWG3 in patients with metastatic CRPC.
Measure:PSA Tumor Marker
Time Frame:Baseline, Day1 of each cycle (each cycle is 28 days), and End of Treatment ( up to approximately 24 months)
Safety Issue:
Description:PSA response greater than or equal to 50% for patients with metastatic CRPC.
Measure:CA-125 Tumor Marker
Time Frame:Baseline, Day1 of each cycle (each cycle is 28 days), and End of Treatment (up to approximately 24 months)
Safety Issue:
Description:CA-125 response for patients with ovarian cancer.
Measure:Biomarker PD-L1
Time Frame:Baseline
Safety Issue:
Description:PD-L1 expression level in baseline tumor tissue.
Measure:Genomic
Time Frame:Baseline
Safety Issue:
Description:Genomic scarring and the presence of defects in select genes, considered critical to effective DDR, in baseline tumor tissue.
Measure:Serum concentrations of avelumab
Time Frame:Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1
Safety Issue:
Description:Pharmacokinetic parameters: maximum concentrations (Cmax)
Measure:Plasma concentrations of talazoparib
Time Frame:Day 1 Cycles 1-4 and Day 15 Cycle 1
Safety Issue:
Description:Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
Measure:Plasma concentration of talazoparib
Time Frame:Day 1 Cycles 1-4 and Day 15 Cycle 1
Safety Issue:
Description:Pharmacokinetic parameters: post-dose concentrations
Measure:Neutralizing antibodies (Nab) levels against avelumab.
Time Frame:Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1
Safety Issue:
Description:Immunogenicity assessment of avelumab
Measure:Time to Tumor Response (TTR)
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:Time to Tumor Response (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:Duration of Response (DR) is defined for patients with confirmed objective response (complete response [CR] or partial response [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:Progression Free Survival (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:Prostate-Specific Antigen (PSA) response
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:PSA response is defined as the proportion of patients with confirmed PSA decline greater than or equal to 50% compared to baseline.
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.

Details

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

Trial Keywords

  • NSCLC, TNBC, hormone receptor positive (HR+) breast cancer, recurrent epithelial ovarian cancer, UC, and castration resistant prostate cancer (CRPC).

Last Updated

November 4, 2017