Clinical trial NCT05397496: Study of PIT565 in Relapsed and/or Refractory B-cell Malignancies
Official title: A Phase I, Open-label, Multi-center Study of PIT565 in Patients With Relapsed and/or Refractory B-cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: B-cell Non-Hodgkin Lymphoma (B-NHL)
B-cell Acute Lymphoblastic Leukemia (B-ALL)
Keywords: Phase I
Trispecific antibody
Non-Hodgkin lymphoma
Acute Lymphoblastic Leukemia
PIT565
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-05-31
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and severity of Dose Limiting Toxicities (DLTs)
timeFrame: 28 days or 35 days, depending on the dosing schedule
measure: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 21 months
measure: Frequency of dose interruptions
timeFrame: 21 months
measure: Frequency of dose reductions
timeFrame: 21 months
measure: Dose intensities
timeFrame: 21 months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 21 months
measure: Complete Response (CR) rate
timeFrame: 21 months
measure: Best Overall Response (BOR)
timeFrame: 21 months
measure: Duration Of Response (DOR)
timeFrame: 21 months
measure: Overall Survival (OS)
timeFrame: 33 months
measure: Progression Free Survival (PFS)
timeFrame: 21 months
measure: Event-free survival (EFS)
timeFrame: 21 months
measure: Maximum concentration of PIT565 (Cmax)
timeFrame: 21 months
measure: Area Under the Curve of PIT565 (AUC)
timeFrame: 21 months
measure: Trough concentration of PIT565 (C trough)
timeFrame: 21 months
measure: Prevalence of Anti-drug antibodies (ADA) at baseline
timeFrame: Baseline
measure: Incidence of Anti-drug antibodies (ADA) on treatment
timeFrame: 21 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Ctr
state: New York
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Reggio Emilia
country: Italy
facility: Novartis Investigative Site
state: RE
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
Study officials:
References: