Study of PIT565 in Relapsed and/or Refractory B-cell Malignancies

A Phase I, Open-label, Multi-center Study of PIT565 in Patients With Relapsed and/or Refractory B-cell Malignancies

This is an open-label, multicenter, phase I study, which primary objective is to characterize the safety and tolerability of PIT565 and to identify maximal tolerated doses (MTDs) and/or recommended doses (RDs), schedule and route of administration in relapsed and/or refractory B-cell Non-Hodgkin lymphoma (R/R B-NHL) and relapsed and/or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

Study Overview

• Status: Active, not recruiting
• Conditions: B-cell Non-Hodgkin Lymphoma (B-NHL); B-cell Acute Lymphoblastic Leukemia (B-ALL)
• Intervention / Treatment: Biological: PIT565

Detailed Description

This is an open-label, multicenter, phase I study of PIT565 in patients with R/R B-NHL and R/R B-ALL.

The study comprises a dose escalation part of PIT565 in two independent groups (group A: R/R B-NHL and B: R/R B-ALL) and a dose expansion part in three independent groups (R/R large B-cell lymphoma (LBCL) randomized in 1:1 ratio to two RDs (A1 and A2), and R/R B-ALL (B1)).

During the dose escalation, the safety (including the dose-dose limiting toxicity (DLT) relationship) and tolerability of PIT565 will be assessed, and schedule(s), route(s) of administration and dose(s) will be identified for use in the expansion part based on the review of these data. The RD will also be guided by the available information on pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity. The dose escalation will be guided by an adaptive Bayesian logistic regression model (BLRM) following the Escalation with Overdose Control (EWOC) principle.

Different schedules and routes of administrations will be explored in the dose escalation groups.

The dose expansion will further explore the MTD(s) and/or RD(s) and the selected schedule(s) and route of administration(s) in the three patients' groups.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Shanghai, China, 200032
    • Novartis Investigative Site
  • Tianjin, China, 300020
    • Novartis Investigative Site
• France
  • Créteil, France, 94010
    • Novartis Investigative Site
  • Marseille, France, 13273
    • Novartis Investigative Site
• Israel
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Novartis Investigative Site
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Novartis Investigative Site
  • Barcelona, Spain, 08036
    • Novartis Investigative Site
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Clinical Research Ctr
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Ctr
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.
• Male or female patients ≥18 years of age at the date of signing the informed consent form
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2

NHL patient population

• Refractory or relapsed B-NHL
• Must have relapsed after or failed to respond to at least two prior treatment therapies including an αCD20 monoclonal antibody containing chemotherapy combination regimen
• Must have at least one bi-dimensionally measurable nodal lesion or one bi-dimensionally measurable extranodal lesion, as measured on positron emission tomography-computed tomography (PET/CT) scan

ALL patient population

• Refractory or relapsed CD19-positive B-ALL
• Morphologic disease in the bone marrow (≥ 5% blasts)

Exclusion Criteria:

• History of severe hypersensitivity to any ingredient of the study treatment or its excipients
• Contraindication to tocilizumab
• History of ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection
• Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type
• Active central nervous system (CNS) involvement by malignancy or presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within the 2 weeks prior to the start of study treatment
• Active, known or suspected autoimmune disease other than patients with vitiligo, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur
• Patients receiving systemic treatment with any immunosuppressive medication

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PIT565 Group A (dose escalation part); PIT565 in adult NHL patients for whom two or more lines of chemotherapy have failed and either having progressed (or relapsed) after autologous hematopoietic stem cell transplantation (HSCT), or being ineligible for or not consenting to the procedure	Biological: PIT565; Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
Experimental: PIT565 Group B (dose escalation part); PIT565 in adult R/R ALL patients.	Biological: PIT565; Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
Experimental: PIT565 Group A1 (dose expansion part); PIT565 Recommended dose 1 (RD1) in adult R/R large B-cell lymphoma (LBCL) (DLBCL, double/triple hit High-grade B-cell lymphoma (HGBCL), Primary mediastinal large B-cell lymphoma (PMBCL), Follicular lymphoma grade 3B (FL3B)) patients.	Biological: PIT565; Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
Experimental: PIT565 Group A2 (dose expansion part); PIT565 RD2 in adult R/R LBCL (DLBCL, double/triple hit HGBCL, PMBCL, FL3B) patients.	Biological: PIT565; Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
Experimental: PIT565 Group B1 (dose expansion part); PIT565 in adult R/R ALL patients.	Biological: PIT565; Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Dose Limiting Toxicities (DLTs)	Assessment of safety of study drug. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of CTCAE grade 3 or higher that occurs within the DLT evaluation period (28 days or 35 days depending on the schedule) and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications with exceptions provided in the clinical protocol.	28 days or 35 days, depending on the dosing schedule
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Assessment of safety of study drug.	21 months
Frequency of dose interruptions	Assessment of tolerability of study drug	21 months
Frequency of dose reductions	Assessment of tolerability of study drug	21 months
Dose intensities	Assessment of tolerability of study drug Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure.	21 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Complete Response (CR) rate	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Best Overall Response (BOR)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Duration Of Response (DOR)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Overall Survival (OS)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	33 months
Progression Free Survival (PFS)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Event-free survival (EFS)	Evaluation of anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Maximum concentration of PIT565 (Cmax)	Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)	21 months
Area Under the Curve of PIT565 (AUC)	Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)	21 months
Trough concentration of PIT565 (C trough)	Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)	21 months
Prevalence of Anti-drug antibodies (ADA) at baseline	Assessment of anti-PIT565 antibodies in serum.	Baseline
Incidence of Anti-drug antibodies (ADA) on treatment	Assessment of anti-PIT565 antibodies in serum.	21 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): August 20, 2026

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: May 25, 2022
• First Posted (Actual): May 31, 2022

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Phase I; Acute Lymphoblastic Leukemia; Non-Hodgkin lymphoma; Trispecific antibody; PIT565
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; Hematologic Diseases; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Leukemia, Lymphoid; Leukemia; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: CPIT565A12101; 2022-000367-45 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No