Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100)

NCT03642132 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: B99910302017-004456-30JAVELIN OVARIAN PARP 100
• Study Type: interventional
• Target: 79
• Locations: 10 countries
• Sites: 72

Brief Summary

JAVELIN Ovarian PARP 100 (B9991030) is an open-label, randomized study designed to evaluate the efficacy and safety of avelumab in combination with chemotherapy followed by maintenance therapy of avelumab in combination with talazoparib versus an active comparator in treatment-naïve patients with locally advanced or metastatic ovarian cancer (Stage III or Stage IV). On March 19, 2019, Sponsors alliance announced the discontinuation of the ongoing Phase III study, and the decision was based on several factors, including previous announced interim results from JAVELIN Ovarian 100 study (B9991010). Patients who remain in B9991030 study will continue receiving their randomized treatment assigned and will be monitored for appropriate safety assessments until treatment discontinuation.

Conditions

Ovarian Cancer

Keywords

untreated epithelial ovarian cancer; fallopian tube cancer; primary peritoneal cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (Participants With Newly Diagnosed Advanced Ovarian Cancer With Defects in DDR+）

  Progression-free survival (PFS) was defined as the time from randomization to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.

  At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by Blinded Independent Central Review (BICR) regardless of initiation of new anti-cancer therapy

Secondary Outcomes (16)

• Number of Participants With Treatment-Emergent Adverse Events (On-Treatment Period)

  From the first dose of study treatment through up to 30 days after minimum last dose of study treatment or start day of new anti-cancer drug therapy minus 1 day (maximum up to 3.5 years approximately)

• Number of Participants With ADA Against Avelumab by Never and Ever Positive Status

  Day 1 pre-dose of Cycles 1, 2, 3, and 4 in the chemotherapy period and Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period and at the end of treatment/withdrawal, up to 27 months.

• Pre-dose/Trough Concentration (Ctrough) for Avelumab (Chemotherapy Period)

  Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)

• Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period)

  Pre-dose on Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period (1 cycle = 6 weeks) and at the end of treatment, up to 27 months.

• Cmax for Avelumab (Chemotherapy Period)

  Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)

Study Arms (3)

chemotherapy, avelumab and talazoparib

EXPERIMENTAL

Platinum-based chemotherapy + avelumab followed by avelumab + talazoparib maintenance

Drug: Chemotherapy + avelumab followed by avelumab + talazoparib

chemotherapy, and talazoparib

EXPERIMENTAL

Platinum-based chemotherapy followed by talazoparib maintenance

Drug: Chemotherapy followed by talazoparib maintenance

chemotherapy and bevacizumab

ACTIVE COMPARATOR

Platinum-based chemotherapy + bevacizumab followed by bevacizumab maintenance

Drug: Chemotherapy + bevacizumab followed by bevacizumab

Interventions

Chemotherapy + avelumab followed by avelumab + talazoparib DRUG

Chemotherapy Period Paclitaxel Carboplatin Avelumab Maintenance Period Avelumab Talazoparib

chemotherapy, avelumab and talazoparib

Chemotherapy followed by talazoparib maintenance DRUG

Chemotherapy Period Paclitaxel Carboplatin Maintenance Period Talazoparib

chemotherapy, and talazoparib

Chemotherapy + bevacizumab followed by bevacizumab DRUG

Chemotherapy Period Paclitaxel Carboplatin Bevacizumab Maintenance Period Bevacizumab

chemotherapy and bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed Stage III IV epithelial ovarian, fallopian tube, or primary peritoneal cancer including carcinosarcoma with high-grade serous component.
• Patients must be candidates for bevacizumab in combination with platinum based chemotherapy and previously untreated.
• Must have completed a primary surgical debulking procedure, or be candidates for neoadjuvant chemotherapy with planned interval debulking surgery.
• Patients who completed primary debulking must have had incompletely resected disease that is macroscopically/grossly visible and at least with lesions \>1 mm and be randomized at a maximum of 8 weeks after surgery.
• For patients who are candidates for neoadjuvant chemotherapy, the diagnoses must have been confirmed by:
• Core tissue (not fine-needle aspiration) biopsy is required for diagnosis.
• Stage IIIC-IV documented via imaging or surgery (without attempt at cytoreduction).
• Serum CA-125/CEA ratio \>25. If the serum CA-125/CEA ratio is \<25, then workup should be negative for the presence of a primary gastrointestinal or breast malignancy (\<6 weeks before start of neoadjuvant treatment).
• Randomization must occur within 8 weeks after diagnosis.
• Availability of an archival FFPE tumor tissue block or a minimum of 25 slides, together with an accompanying original H\&E slide. If archived FFPE tissue is not available, a de novo (ie, fresh) tumor sample must be obtained in accordance with local institutional practice for tumor biopsies. Tumor tissue must contain 40% or greater tumor nuclei per central laboratory assessment.
• ECOG performance status 0-1
• Age \>=18 years (or \>=20 years in Japan).
• Adequate bone marrow, hepatic, and renal function and blood coagulation

You may not qualify if:

• Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors.
• Patients for whom intraperitoneal cytotoxic chemotherapy is planned.
• Prior exposure to immunotherapy with interleukin (IL)-2, interferon alpha (IFN-α), or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, excluding therapeutic anticancer vaccines.
• Prior treatment with a PARP inhibitor.
• Prior treatment with any anti-vascular endothelial growth factor (VEGF) drug, including bevacizumab.
• Major surgery (other than debulking or exploratory surgery for ovarian cancer) for any reason within 4 weeks prior to randomization and/or incomplete recovery from surgery.
• Prior radiotherapy to any portion of the abdominal cavity or pelvis. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease.
• Prior targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their ovarian, peritoneal primary or fallopian tube carcinoma.
• Prior organ transplantation including allogenic stem cell transplantation.
• Diagnosis of Myelodysplastic Syndrome (MDS).
• Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (72)

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, 85016, United States

Location

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, 85027, United States

Location

Arizona Oncology Associates, PC - HAL

Scottsdale, Arizona, 85258, United States

Location

Arizona Oncology Associates, PC - HAL

Tempe, Arizona, 85284, United States

Location

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85704, United States

Location

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85711, United States

Location

Sansum Clinic

Santa Barbara, California, 93105, United States

Location

Sansum Clinic

Solvang, California, 93463, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06510, United States

Location

NYU Winthrop Hospital, Gynecologic Oncology

Mineola, New York, 11501, United States

Location

NYU Winthrop Hospital, Infusion Center

Mineola, New York, 11501, United States

Location

NYU Winthrop Radiology

Mineola, New York, 11501, United States

Location

Montefiore Medical Center - EPC

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center, Department of Obstetrics and Gynecology and Women's Health

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center-Centennial Facility

The Bronx, New York, 10467, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45211, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45230, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45236, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97213-2982, United States

Location

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97225, United States

Location

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97227, United States

Location

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, 97062, United States

Location

Tennessee Oncology, PLLC

Dickson, Tennessee, 37055, United States

Location

Tennessee Oncology, PLLC

Franklin, Tennessee, 37067, United States

Location

Tennessee Oncology, PLLC

Gallatin, Tennessee, 37066, United States

Location

Tennessee Oncology, PLLC

Hermitage, Tennessee, 37076, United States

Location

Tennessee Oncology, PLLC

Lebanon, Tennessee, 37090, United States

Location

Tennessee Oncology, PLLC

Murfreesboro, Tennessee, 37129, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37205, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37207, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37211, United States

Location

Tennessee Oncology, PLLC

Shelbyville, Tennessee, 37160, United States

Location

Tennessee Oncology, PLLC

Smyrna, Tennessee, 37167, United States

Location

Texas Oncology Bedford

Bedford, Texas, 76022, United States

Location

Texas Oncology

Fort Worth, Texas, 76104, United States

Location

US Oncology Investigational Products Center (IPC)

Irving, Texas, 75063, United States

Location

US Oncology Investigational Products Center

Irving, Texas, 75063, United States

Location

Texas Oncology- San Antonio

San Antonio, Texas, 78240, United States

Location

Virginia Oncology Associates

Chesapeake, Virginia, 23320, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Virginia Oncology Associates

Virginia Beach, Virginia, 23456, United States

Location

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98684, United States

Location

Epworth Foundation trading as Epworth HealthCare

East Melbourne, Victoria, 3002, Australia

Location

Epworth HealthCare, Clinical Trials & Research Centre

Richmond, Victoria, 3121, Australia

Location

CHU-UCL Namur/Site Sainte Elisabeth

Namur, 5000, Belgium

Location

Bon Secours Hospital

Cork, T12 DV56, Ireland

Location

Istituto Europeo di Oncologia (IEO)

Milan, MI, 20141, Italy

Location

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, RM, 00168, Italy

Location

Niigata Cancer Center Hospital

Niigata, 951-8566, Japan

Location

Limited Liability Company "VitaMed" (LLC "VitaMed")

Moscow, 121309, Russia

Location

Department of Nuclear Medicine and Molecular Imaging

Singapore, 169608, Singapore

Location

SingHealth Investigational Medicine Unit

Singapore, 169608, Singapore

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Department of Pathology

Singapore, 169856, Singapore

Location

Raffles Hospital

Singapore, 188770, Singapore

Location

Raffles Radiology

Singapore, 188770, Singapore

Location

Farrer Park Hospital

Singapore, 217562, Singapore

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital

Seoul, 06229, South Korea

Location

Gangnam Severance Hospital

Seoul, 06273, South Korea

Location

Clinical Trial Pharmacy, Samsung Medical Center

Seoul, 06351, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center

Taipei, 112, Taiwan

Location

Division of Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center

Taipei, 112, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, 112, Taiwan

Location

Related Publications (1)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Drug Therapy; talazoparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Limitations and Caveats

As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. A total of 104 participants were screened and 79 participants completed screening and randomized in the study before study discontinuation. As only 11% projected enrollment was met at the time of enrollment stop, the original study endpoints are no longer applicable and/or feasible; only the Safety, PK and Immunogenicity Analysis were done and these data are included in this report.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: August 22, 2018
• Study Start: July 19, 2018
• Primary Completion: December 22, 2021
• Study Completion: December 22, 2021
• Last Updated: April 6, 2023
• Results First Posted: April 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

US (46); BE (1); SG (7); KR (7); IE (1); RU (1); AU (2); JP (1); IT (2); TW (4)