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

Status: Active

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).

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, CRPC, and other advanced solid tumors with a BRCA or ATM gene defect
  • 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.
  • Pregnant, breastfeeding females or female patients able to have children must agree to use highly effective method of contraception throughout the study and for at least 30 days after the last dose of avelumab and for at least 7 months after the last dose of talazoparib; fertile male patients must use a condom during treatment and for at least 4 months after the last dose of talazoparib.
  • 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. For cohort A2 NSCLC patients prior treatment with anti-PD-1/L1 is allowed
  • Prior anti-cancer therapy within 2 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 within 7 days prior to first dose of study drug, or anticipated use during the study of a strong P-gp inhibitor.
  • Other acute or chronic medical or psychiatric conditions.

Locations & Contacts

California

Los Angeles
USC / Norris Comprehensive Cancer Center
Status: Active
Contact: Cheryl Kefauver
Phone: 323-865-0845
Email: Cheryl.Kefauver@med.usc.edu
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Name Not Available
San Diego
University of California San Diego
Status: In review
Name Not Available

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: Active
Name Not Available

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Name Not Available

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Name Not Available
New York
Icahn School of Medicine at Mount Sinai
Status: Active
Name Not Available

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: Active
Name Not Available

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: Active
Contact: SCC Clinical Trials Office
Phone: 405-271-8777
Email: SCC-Clinical-Trials-Office@ouhsc.edu

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

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 Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Pfizer

Trial IDs

Primary ID B9991025
Secondary IDs NCI-2017-02385, 2017-001509-33, JAVELIN PARP MEDLEY
Clinicaltrials.gov ID NCT03330405