TEMPUS STUDIES

PAVO: A Tempus Study of PALB2

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

PAVO is an open-label phase II study investigating whether niraparib (Zejula®), a PARP inhibitor, is safe and effective for certain patients with a locally advanced or metastatic solid tumor and a germline or somatic PALB2 mutation.

PALB2 is a protein that helps normal cells repair changes in DNA.  If a patient carries a mutation in PALB2, cancer cells can grow more rapidly leading to an increased risk of some cancers such as breast and pancreatic cancer. The study drug niraparib can target and kill cancer cells.

Niraparib is already approved by the FDA for other uses with years of clinical research data. All PAVO study participants will receive niraparib at no cost and it will be given orally once daily throughout each 28-day cycle. Subjects will have routine blood tests and will be evaluated by CT or MRI scans every 8 weeks for approximately one year.

Key Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of a locally advanced or metastatic solid tumor(s)
  • Must have locally advanced or metastatic disease
  • Positive test for a pathogenic or likely pathogenic PALB2 gene mutation (germline or somatic) 
  • If clinically feasible, must submit FFPE archival tissue, fresh tumor tissue or a liquid biopsy, representative of current tumor status

Key Exclusion Criteria

  • Participants with ovarian or prostate cancer
  • PALB2 mutation(s) categorized as a variants of undetermined significance (VUS), at the time of screening
  • A germline or somatic BRCA1 or BRCA2 mutation
  • Participants who have received prior PARP inhibitor(s) in prior lines of treatment
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Background

About PALB2 mutations and PARP inhibitors

The PALB2 mutation is present in a variety of solid tumors, such as a prevalence of 1.8% in brain cancer and 3.8% in bladder cancer. While present at a much lower frequency than BRCA1/2, PALB2 is similarly associated with an increased risk of cancer.<sup>1</sup> Recent studies demonstrate that patients with metastatic breast or advanced pancreatic cancers with germline PALB2 mutations have achieved clinical benefit from treatment with PARP inhibitors.<sup>2,3</sup>

Similar to BRCA I/2, PALB2 is also considered a potent regulator of the homologous recombination repair (HRR) pathway and mutations in PALB2 can result in homologous recombination repair deficiency (HRD). Cancer cells with HRD cannot repair DNA damage and are more sensitive to PARP inhibition.

  1. Hofstatter, Erin W, et al. “PALB2 Mutations in Familial Breast and Pancreatic Cancer.” Familial Cancer, U.S. National Library of Medicine, June 2011, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836668/.
  2. Reiss KA;Mick R;O’Hara MH;Teitelbaum U;Karasic TB;Schneider C;Cowden S;Southwell T;Romeo J;Izgur N;Hannan ZM;Tondon R;Nathanson K;Vonderheide RH;Wattenberg MM;Beatty G;Domchek SM; “Phase II Study of Maintenance Rucaparib in Patients with Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or palb2.” Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/33970687/.
  3. Nadine M. Tung; Mark E. Robson; Steffen Ventz; Cesar A. Santa-Maria; Rita Nanda;Paul K. Marcom; Payal D. Shah; Tarah J. Ballinger\; Eddy S. Yang, MD; Shaveta Vinayak; Michelle Melisko; Adam Brufsky; Michelle DeMeo; Colby Jenkins; Susan Domchek;Alan D’Andrea; Nancy U. Lin; Melissa E. Hughes; Lisa A. Carey;Nick Wagle;Gerburg M. Wulf; Ian E. Krop; Antonio C. Wolff; Eric P. Winer; and Judy E. Garber. “TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.” Journal of Clinical Oncology https://doi. org/10.1200/JCO.20. 02151

Gather more information about the study, including the complete list of inclusion and exclusion criteria.

Individuals interested in joining the study should talk with their doctor.

View the PAVO Study, NCT05169437

PAVO Study Contact Information

For additional information and inquiries, please send an email to pavo@tempus.com.