Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors (PAVO)

A Single-Arm Phase-II Study of Niraparib in Locally Advanced or Metastatic Solid Tumor Patients With PALB2 Mutations

The purpose of this study is to further evaluate the efficacy and safety of niraparib in patients with locally advanced or metastatic solid tumors and a pathogenic or likely pathogenic tumor PALB2 (tPALB2) mutation.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Head and Neck Cancer; Pancreatic Cancer; Esophageal Cancer; Solid Tumor; Metastatic Cancer; Endometrial Cancer; Urologic Cancer; Breast Tumor; Locally Advanced Solid Tumor; Lung Tumor; Colon Tumor, Malignant
• Intervention / Treatment: Drug: Niraparib

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology
  • California
    • Fountain Valley, California, United States, 92708
      • Memorial Care Medical Center
    • Fullerton, California, United States, 92835
      • St Joseph Heritage Health - Fullerton
    • La Jolla, California, United States, 92093-0698
      • University of California San Diego
    • Long Beach, California, United States, 90806
      • MemorialCare
    • Los Alamitos, California, United States, 90720
      • Cancer and Blood Specialty Clinic
    • Los Alamitos, California, United States, 90720
      • Cancer and Blood Specialty
    • Los Angeles, California, United States, 90404
      • University of California Los Angeles
    • Napa, California, United States, 94558
      • St Joseph Health Medical Group - Napa
    • Oxnard, California, United States, 93030
      • Ventura County Hematology Oncology Specialists
    • San Diego, California, United States, 92123
      • Sharp HealthCare
    • Santa Barbara, California, United States, 93105
      • Ridley-Tree Cancer Center
    • Santa Rosa, California, United States, 95403
      • St Joseph Health Medical Group - Santa Rosa
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford HealthCare
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross
    • Jacksonville, Florida, United States, 32256
      • Cancer Specialists of North Florida
    • Ocala, Florida, United States, 34474
      • Ocala Community Cancer Center
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Rolling Meadows, Illinois, United States, 60008
      • Northwest Oncology & Hematology
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology
    • Goshen, Indiana, United States, 46526
      • Goshen Health
    • Indianapolis, Indiana, United States, 46250
      • Community Health Network
    • South Bend, Indiana, United States, 46601
      • Beacon Health System
  • Louisiana
    • Hammond, Louisiana, United States, 70403
      • Pontchartrain Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • The Center for Cancer and Blood Disorders - Maryland
    • Frederick, Maryland, United States, 21702
      • Frederick Health
    • Rockville, Maryland, United States, 20850
      • Maryland Oncology Hematology
  • Massachusetts
    • Fairhaven, Massachusetts, United States, 02719
      • Southcoast Health
  • Michigan
    • Lansing, Michigan, United States, 48912
      • Sparrow Health
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center
    • Saint Joseph, Missouri, United States, 64507
      • Mosaic Life Care
    • Springfield, Missouri, United States, 65807
      • Oncology Hematology Associates
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • OptumCare Cancer Care
  • New Jersey
    • Belleville, New Jersey, United States, 07109
      • New Jersey Cancer Care and Blood Disorders
    • Englewood, New Jersey, United States, 07631
      • Englewood Health
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Inc. - Charlotte
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Inc. - Winston-Salem
  • Ohio
    • Canton, Ohio, United States, 44708
      • Aultman Medical Group
    • Cincinnati, Ohio, United States, 45220
      • TriHealth
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Seidman
    • Columbus, Ohio, United States, 43214
      • OhioHealth
    • Toledo, Ohio, United States, 43623
      • The Toledo Clinic
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists
  • Oregon
    • Salem, Oregon, United States, 97301
      • Oregon Oncology Specialists
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Gettysburg Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Bon Secours - St. Francis Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57117
      • Sanford Health
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Cancer Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Austin, Texas, United States, 78745
      • Texas Oncology - South Austin
    • Austin, Texas, United States, 78705
      • Texas Oncology - Austin Midtown
    • Austin, Texas, United States, 78731
      • Texas Oncology - Austin Central Pharmacy
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Oncology Consultants
    • Longview, Texas, United States, 75601
      • Texas Oncology - Longview Cancer Center
    • Palestine, Texas, United States, 75801
      • Texas Oncology - Palestine Cancer Center
    • Paris, Texas, United States, 75460
      • Texas Oncology - Paris Cancer Center
    • Sugar Land, Texas, United States, 77479
      • Lumi Research
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler Pharmacy
  • Utah
    • Ogden, Utah, United States, 84405
      • Community Cancer Trials of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Institute
    • Fredericksburg, Virginia, United States, 22408
      • Hematology Oncology Associates of Fredericksburg
    • Richmond, Virginia, United States, 23230
      • Virginia Cancer Institute
    • Richmond, Virginia, United States, 23229
      • Virginia Cancer Institute
  • Washington
    • Bellingham, Washington, United States, 98225
      • PeaceHealth
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties
  • Wisconsin
    • Appleton, Wisconsin, United States, 54911
      • ThedaCare
    • Madison, Wisconsin, United States, 53717
      • SSM Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must be at least 18 years of age or older.
• Participants must have a histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor(s).
• Participants must have tested positive for a pathogenic or likely pathogenic tPALB2 gene mutation using a CLIA-certified laboratory as described in the Next-Generation Sequencing (NGS) Laboratory Manual.
• Participants who have stable and asymptomatic Central Nervous System (CNS) disease must be receiving a stable (for at least 7 days) or decreasing corticosteroid dose at the time of study entry.
• Participants must submit fresh or archived (collected within 24 months of enrollment) Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample to the central laboratory for post-enrollment confirmation of tPALB2 status.
• Participants must have received all standard therapies appropriate for their tumor type and stage of disease or, in the opinion of the Investigator, the patient would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy, or the participant has no satisfactory alternative treatments.

Exclusion Criteria:

• Participants have other active concomitant malignancy that warrants systemic, biologic, or hormonal therapy.
• Participants who have ovarian or prostate cancer.
• Participants who have variants of undetermined significance (VUS), but not pathogenic variants of PALB2, at the time of screening.
• Participants who relapsed while receiving platinum based therapy in the adjuvant/curative setting.
• Participants progressing within 14-18 weeks while receiving platinum based therapy in the metastatic setting.
• Participants who have received Poly (ADP-ribose) polymerase (PARP) inhibitor(s) in prior lines of treatment.
• Participants with leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiologic signs of CNS hemorrhage.
• Participants with germline or somatic BRCA1 or BRCA2 mutations.
• Participant has systolic blood pressure (BP) over 140 mmHg or diastolic BP over 90 mmHg, despite optimal medical therapy.
• Participants have previously or are currently participating in a treatment study of an investigational agent within 3 weeks of the first dose of therapy preceding the study.
• Participants have received prior systemic cytotoxic chemotherapy, biological therapy, or hormonal therapy for cancer, or received radiation therapy within 3 weeks of the first dose therapy preceding the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Niraparib in Locally Advanced or Metastatic Solid Tumor Patients with PALB2 Mutations	Drug: Niraparib; Eligible participants will receive daily dosing of Niraparib.; Other Names: Zejula

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) - Independent Central Review (ICR)	To evaluate overall response rate (ORR) as assessed by Independent Central Review (ICR) using RECIST v1.1	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) - Independent Central Review (ICR)	To evaluate duration of response (DOR) as assessed by ICR using RECIST v1.1	Up to 4 years
Progression-Free Survival (PFS) - Independent Central Review (ICR)	To evaluate progression-free survival (PFS) as assessed by ICR using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)	Up to 4 years
Overall Response Rate (ORR) - Investigator	To evaluate ORR as defined as the proportion of patients who had a partial or complete response (PR or CR) to therapy, as assessed by Investigator using RECIST v1.1 and assessed periodically throughout the treatment period based on imaging every 8 weeks (56 ± 7 days).	2 years 3 months
Duration of Response (DOR) - Investigator	To evaluate DOR as assessed by Investigator using RECIST v1.1 defined as from first documentation of objective tumor response (CR or PR) to first documentation of objective tumor progression or death due to any cause.	2 years 3 months
Progression-Free Survival (PFS) - Investigator	To evaluate PFS as assessed by Investigator using RECIST v1.1 determined from the first dose to the date of first radiographic progression or death from any cause in the absence of progression, whichever occurred first, or were censored.	2 years 3 months
Clinical Benefit Rate (CBR) - Investigator and ICR	To evaluate Clinical Benefit Rate (CBR), defined as the percentage of patients who had achieved Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for 8 weeks or more, as assessed by Investigator only (ICR not performed due to early study termination).	2 years 3 months
ORR With Untreated Measurable CNS Lesions - Investigator	To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by Investigator using RECIST v1.1	Up to 4 years
ORR With Untreated Measurable CNS Lesions - ICR	To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by ICR using RECIST v1.1	Up to 4 years
Number of Participants With Treatment-Emergent Adverse Events	To evaluate safety and tolerability per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)	2 years 3 months
Overall Survival (OS)	To evaluate overall survival (OS) defined as the time from the date of first dose of study drug to the date of death by any cause. Patients who were alive were censored at the date of last contact.	6 months and 12 months

Collaborators and Investigators

• Sponsor: Tempus AI
• Collaborators: GlaxoSmithKline
• Investigators: Study Director: Virginia Rhodes, Tempus AI, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2022
• Primary Completion (Actual): August 6, 2024
• Study Completion (Actual): August 27, 2024

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: December 22, 2021
• First Posted (Actual): December 27, 2021

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 15, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Niraparib; Pancreatic Cancer; Melanoma; Solid Tumor; Endometrial Cancer; Metastatic Cancer; Esophageal Cancer; Advanced Solid Tumor; Metastatic Solid Tumor; PALB2; Lung Tumor; Breast Tumor; Locally Advanced Solid Tumor; Local Solid Tumor; PALB2 Mutation; tPALB2; tPALB2 Mutation; Pathogenic tumor; Colon Tumor; Zejula; Urologic Cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Neoplastic Processes; Esophageal Diseases; Genital Neoplasms, Female; Skin Diseases; Breast Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Uterine Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Lung Neoplasms; Colonic Neoplasms; Esophageal Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Head and Neck Neoplasms; Melanoma; Urologic Neoplasms; Endometrial Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; niraparib
• Other Study ID Numbers: TMPS-101; IND Number: 159142 (Other Identifier: FDA)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No