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

• ClinicalTrials.gov Identifier: NCT05169437
• Recruitment Status: Recruiting
• First Posted: December 27, 2021
• Last Update Posted: May 6, 2023
• Sponsor: Tempus Labs
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Tempus Labs

Tracking Information

• First Submitted Date: December 13, 2021
• First Posted Date: December 27, 2021
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: March 15, 2022
• Estimated Primary Completion Date: June 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 22, 2021)

Overall Response Rate (ORR) - Independent Central Review (ICR) [ Time Frame: Up to 4 years ]

To evaluate overall response rate (ORR) as assessed by Independent Central Review (ICR) using RECIST v1.1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 22, 2021)

• Duration of Response (DOR) - Independent Central Review (ICR) [ Time Frame: Up to 4 years ]
  To evaluate duration of response (DOR) as assessed by ICR using RECIST v1.1
• Progression-Free Survival (PFS) - Independent Central Review (ICR) [ Time Frame: Up to 4 years ]
  To evaluate progression-free survival (PFS) as assessed by ICR using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Overall Response Rate (ORR) - Investigator [ Time Frame: Up to 4 years ]
  To evaluate ORR as assessed by Investigator using RECIST v1.1
• Duration of Response (DOR) - Investigator [ Time Frame: Up to 4 years ]
  To evaluate DOR as assessed by Investigator using RECIST v1.1
• Progression-Free Survival (PFS) - Investigator [ Time Frame: Up to 4 years ]
  To evaluate PFS as assessed by Investigator using RECIST v1.1
• Clinical Benefit Rate (CBR) - Investigator and ICR [ Time Frame: Up to 4 years ]
  To evaluate Clinical Benefit Rate (CBR) as assessed by ICR and Investigator
• ORR with untreated measurable CNS lesions - Investigator [ Time Frame: Up to 4 years ]
  To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by Investigator using RECIST v1.1
• ORR with untreated measurable CNS lesions - ICR [ Time Frame: Up to 4 years ]
  To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by ICR using RECIST v1.1
• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to 4 years ]
  To evaluate safety and tolerability per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)
• Overall Survival (OS) [ Time Frame: Up to 4 years ]
  To evaluate overall survival (OS)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors
• Official Title: A Single-Arm Phase-II Study of Niraparib in Locally Advanced or Metastatic Solid Tumor Patients With PALB2 Mutations
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumor
• Breast Tumor
• Colon Tumor, Malignant
• Lung Tumor
• Urologic Cancer
• Pancreatic Cancer
• Melanoma
• Metastatic Cancer
• Locally Advanced Solid Tumor
• Esophageal Cancer
• Endometrial Cancer
• Head and Neck Cancer

Intervention

Drug: Niraparib

Eligible participants will receive daily dosing of Niraparib.

Other Name: Zejula

Study Arms

Experimental: Niraparib in Locally Advanced or Metastatic Solid Tumor Patients with PALB2 Mutations

Intervention: Drug: Niraparib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 22, 2021): 110
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 1, 2025
• Estimated Primary Completion Date: June 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Brad Johnson; (630)687-5723; pavo@tempus.com

Contact: Anjali Avadhani, MD; pavo@tempus.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05169437
• Other Study ID Numbers: TMPS-101; IND Number: 159142 ( Other Identifier: FDA )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Tempus Labs
• Original Responsible Party: Same as current
• Current Study Sponsor: Tempus Labs
• Original Study Sponsor: Same as current
• Collaborators: GlaxoSmithKline

Investigators

• Study Director: Anjali Avadhani, MD; Tempus Labs, Inc.

• PRS Account: Tempus Labs
• Verification Date: May 2023