PNT2258 for Treatment of Patients With r/r DLBCL (Wolverine)

A Phase II Study of PNT2258 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It is a multi-center, nonrandomized, open label, phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma, Diffuse Large B-Cell
• Intervention / Treatment: Drug: PNT2258

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion de Investigacion
• United States
  • California
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood and Cancer Institute
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute
    • Winter Haven, Florida, United States, 33880
      • Bond Clinic, P.A.
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research, Inc.
  • Louisiana
    • Lafayette, Louisiana, United States, 70506
      • UHC Oncology
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Western Maryland Health System
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grosse Pointe Woods, Michigan, United States, 48236
      • St. John Hospital and Medical Center
    • Lansing, Michigan, United States, 48910
      • Michigan State University
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Bon Secours Saint Francis Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Avera Research Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor Research Institute
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center
    • Tyler, Texas, United States, 75701
      • Tyler Hematology Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
    • Newport News, Virginia, United States, 23601
      • Peninsula Cancer Institute
  • Washington
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates, PS

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Histologically confirmed diffuse large B-cell lymphoma that is refractory to prior therapy or relapsed after prior therapy.

FDG PET-CT (disease) positive baseline scan with measurable disease.

The patient must have received prior therapy that included:

• CD20-targeted therapy (for example, rituximab),
• Alkylating agent (for example, cyclophosphomide), and
• Steroid, unless the patient is steroid intolerant

Exposure to at least 1 or 2 (but no more than 3) prior systemic cytotoxic chemotherapeutic regimens.

Note: Only those subjects who are not eligible for high-dose chemotherapy and autologous stem cell transplant (HD-ASCT), or who refuse HD-ASCT, are eligible with exposure to only 1 prior cytotoxic chemotherapeutic regimen.

ECOG performance status of 0-1.

The patient must be a stable baseline with CTCAE grade ≤ 2 regarding any acute or chronic toxicity associated with prior therapy, and have discontinued prior anti-cancer therapy for ≥ 14 days prior to C1D1; mitomycin-C for at least 6 weeks prior to C1D1; SCT ≥ 2 months prior to C1D1.

Note: Palliative steroids for control of disease-related symptoms are allowed and maintenance hormone therapy is allowed.

Adequate organ function including:

• Hematologic: ANC ≥ 0.5 x 10^9/L. and platelets ≥ 50 x 10^9/L.
• Hepatic: Total Bilirubin ≤ 2 x ULN (patients with Gilbert's syndrome must have total bilirubin ≤ 3 x ULN) and serum transaminase levels ≤ 2.5 x ULN. In the case of known liver metastasis (i.e., radiological or biopsy documented), serum transaminase levels must be ≤ 5 x ULN.
• Renal: Serum creatinine ≤ 2 x ULN, or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above 2 x ULN.

Willingness to: 1.) undergo pre-treatment biopsy to obtain adequate tissue for analysis (e.g., core needle, excisional or incisional tumor biopsy) or 2.) provide archived tumor (e.g., FFPE block) for analysis.

Exclusion Criteria:

Eligibility for high-dose chemotherapy (HDT) and stem cell transplant (SCT). Note: Subjects who progressed ≥ 2 months after HDT/SCT are eligible

Concurrent malignancies requiring treatment.

Primary mediastinal (thymic) large B-cell lymphoma

Symptomatic CNS or leptomeningeal involvement of lymphoma.

Concurrent clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram or laboratory finding that, in the opinion of the investigator, could adversely affect the safety of the patient or impair the assessment of the study results.

Signs or symptoms of heart failure characterized as greater than NYHA Class II or other significant cardiac abnormalities.

Pregnant or breast-feeding.

Prior exposure to PNT2258.

Life expectancy less than 3 months.

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: PNT2258; PNT2258 will be administered at 120 mg/m2 on days 1-5 of a 21-day cycle. Treatment may continue unless there is disease progression or the occurrence of unacceptable toxicity for a total of 8 "induction" cycles of therapy. Subjects with CR/CMR, PR/PMR or SD/NMR at the end-of-cycle 8 scan then receive ongoing PNT2258 therapy at a dose of 100 mg/m2 on days 1-4 of a 28 day cycle until progressive disease, the occurrence of unacceptable toxicity, non-compliance, voluntary withdrawal or if in the opinion of the investigator the subject is no longer benefiting from exposure to PNT2258.

Drug: PNT2258; Other Names: DNAi, BCL2 targeted therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	The proportion of patients with complete response (CR/complete metabolic response [CMR]) or partial response (PR/partial metabolic response [PMR]) according to the revised 2014 International Working Group (IWG) criteria for lymphoma (Cheson 2014)	19 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate	The proportion of patients who have a response of stable disease (SD/no metabolic response [NMR]) or better by investigator assessment	19 months
Time to Response	The number of months from Cycle 1 Day 1 until the date of the first documented response	19 months
Progression-free Survival	The number of months from C1D1 until the date of DLBCL progression or death from any cause, or to the last date at which progression status was adequately assessed for censored observation	19 months
Safety - Assessment of Adverse Events	Characterization of the type, frequency, severity, timing of onset, duration, and relationship to study drug of any treatment-emergent adverse events, laboratory abnormalities, serious adverse events or adverse events leading to discontinuation of study treatment	36 months
Overall Survival	The number of months from C1D1 until the date of death from any cause, or to the last date at which survival status was adequately assessed for censored observations	19 months
Duration of Overall Response	The time from the initial CMR or PMR until the date of progression or death from any cause, or to the last date at which progression status was adequately assessed for censored observations	19 months

Collaborators and Investigators

• Sponsor: Sierra Oncology LLC - a GSK company
• Investigators: Study Chair: Barbara Klencke, MD, Sierra Oncology LLC - a GSK company

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): July 11, 2016
• Study Completion (Actual): August 22, 2018

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: August 26, 2014
• First Posted (Estimated): August 27, 2014

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: DLBCL; Lymphoma; NHL; Non-Hodgkin's Lymphoma; Diffuse Large B-cell Lymphoma; PNT2258
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: PNT2258-03-DLBCL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED