TEMPUS STUDIES

PAVO: A Pan-Tumor PALB2 PARP Inhibitor Study

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 if the study drug, a PARP inhibitor called niraparib (Zejula), is safe and effective for certain people who have been diagnosed with an advanced solid tumor with either an inherited or tumor PALB2 mutation.

All participants will receive the study drug, niraparib. Study participants will be dosed with niraparib orally once daily throughout each 28-day cycle and be evaluated via CT or MRI scans every 8 weeks for approximately one year.

Key Inclusion Criteria

  • Positive test for a pathogenic PALB2 gene mutation (inherited or tumor)
  • Provide archival tissue representative of current tumor status
  • 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

Key Exclusion Criteria

  • Do not have a histologically or cytologically confirmed diagnosis of an advanced or metastatic solid cancer
  • Ovarian or prostate cancer
  • Variants of undetermined significance (VUS), but not pathogenic variants of PALB2, at the time of screening
  • Inherited or tumor BRCA1 or BRCA2 mutations
  • Received prior PARP inhibitor(s) in prior lines of treatment

Background

About PALB2 mutations and PARP inhibitors

The PALB2-mutation is present in 1.66% of solid tumor patients. While present at a much lower frequency than other HRR-related genes (BRCA1/2), PALB2 is similarly associated with an increased risk of cancer.1

Similar to BRCA, PALB2 is also considered a potent regulator of the homologous recombination repair (HRR) pathway. Therefore, one potential avenue to treat this population is with poly (ADP-ribose) polymerase inhibitors (PARPi) such as niraparib, which prevent DNA damage repair and promote cancer cell cytotoxicity. Recent studies demonstrate that patients with metastatic breast and advanced pancreatic cancers with inherited PALB2 mutations have achieved clinical benefit from treatment with PARP inhibitors.2,3

  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.