Study Description
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). 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
(relapsed and/or refractory large B-cell lymphoma (R/R LBCL) who received CAR-T therapy
(A2) or not (A1), 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 recommended dose (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 (once weekly (Q1W) or once every 2 weeks (Q2W) with and without
priming dose) and routes of administrations (intravenous (i.v.) or subcutaneous (s.c.))
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.
Interventions
PIT565
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
than steroids as described above)
Other protocol-defined inclusion/exclusion criteria may apply.
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