Dose Escalation and Expansion Study of CPO107 for Patients with Advanced CD20-positive Non-Hodgkins Lymphoma

Inclusion Criteria:

The following key inclusion criteria apply to both Part A and Part B:

• Diagnosis of CD20 positive NHL. CD20 assay to have been performed within 6 monthsprior to protocol entry. Eligible NHL subtypes include Diffuse Large B-Cell Lymphoma (DLBCL, not otherwise specified, NOS), Follicular Lymphoma, Chronic lymphocyticleukemia/small lymphocytic lymphoma, B cell prolymphocytic leukemia and Mantle celllymphoma.

• Patients with SLL must have received, or not be eligible for, BTK and BCL-2inhibitor therapy.

• Disease progression or relapse following at least two prior lines of conventionalsystemic therapy for advanced disease. Dosing regimen must have included a CD20targeted therapy (for example, RCHOP).

• A clinical indication for treatment must be present for patients with FollicularLymphoma and Chronic/Small/Prolymphocytic/Mantle B-cell non-Hodgkin lymphoma.

• Having at least one measurable target lesion present and documented by RECIST 1.1.

• Adequate organ function, such as Renal function, Hepatic Function, Cardiovascular,Adequate hematological reserve.

• Complete resolution of all prior toxicities from prior anticancer therapy, definedas having resolved to baseline or to common terminology criteria for adverse events (CTCAE) grade≤1, with the exception of alopecia, or to the levels dictated in theinclusion/exclusion criteria, and a washout period of 5 half-lives of prior smallmolecule systemic therapy.

• Life expectancy >12 weeks.

• Age: Lower age limit of 18 years.

• ECOG performance status 0 or 1 at screening.

• Ability to understand the nature of this study, comply with protocol requirements,and give written informed consent. For minors, legal guardian willingness to givewritten informed consent with patient assent, where appropriate.

• Patients of reproductive potential: All female study participants of reproductivepotential must have a negative serum or urine pregnancy test performed within 48hours before study entry.

Exclusion Criteria:

The following key exclusion criteria apply:

• Patients with indolent Follicular Lymphoma or Chronic/Small/Prolymphocytic/MantleB-cell non-Hodgkin lymphoma in need of immediate cytoreductive therapy are excluded,unless the patient has no remaining treatment choice with potential benefit.

• Patient has participated in any investigational research study and is being screenedfor participation within a period of 5 half-lives, or 4 weeks of the last dose ofthe investigational therapy, whichever is longer.

• Patients with history of severe hypersensitivity reactions to anti-CD20 treatment orany components of study drug formulation.

• Presence or recent history within 6 months of arteritis or any systemic clottingdisorder, thrombotic or thromboembolic events.

• History or presence of autoimmune conditions; patients who have a medical conditionthat requires chronic systemic steroid therapy or requires any other form ofimmunosuppressive medication.

• Patients with a marked baseline prolongation of QT/QTc interval (e.g., repeateddemonstration of a QTc interval >480 milliseconds (ms) (CTCAE grade 1) usingFredericia's QT correction formula.

• Active or latent hepatitis B or active hepatitis C or any uncontrolled infection atscreening; HIV positive test within 8 weeks of screening.

• Serious active infection at the time of treatment, or another serious underlyingmedical condition that would impair the ability of the patient to receive protocoltreatment.

• Presence of other active cancers, or history of treatment for invasive cancer ≤3years.

• Patients who started erythropoietin or granulocyte colony-stimulating factor (G-CSF), pegfilgrastim, or filgrastim ≤4 weeks prior to the first dose of the studydrug.

• Psychological, familial, sociological, or geographical conditions that do not permitcompliance with the protocol.

• Active CNS disease involvement; CNS directed radiation must be completed >8 weeksprior to CPO107 infusion.

• Disease progression or relapse following at least two prior lines of conventional
systemic therapy for advanced disease. Dosing regimen must have included a CD20
targeted therapy (for example, RCHOP).
 

• A clinical indication for treatment must be present for patients with Follicular
Lymphoma and Chronic/Small/Prolymphocytic/Mantle B-cell non-Hodgkin lymphoma.
 

• Having at least one measurable target lesion present and documented by RECIST 1.1.
 

• Adequate organ function, such as Renal function, Hepatic Function, Cardiovascular,
Adequate hematological reserve.
 

• Complete resolution of all prior toxicities from prior anticancer therapy, defined
as having resolved to baseline or to common terminology criteria for adverse events
 (CTCAE) grade≤1, with the exception of alopecia, or to the levels dictated in the
inclusion/exclusion criteria, and a washout period of 5 half-lives of prior small
molecule systemic therapy.
 

• Life expectancy >12 weeks.
 

• Age: Lower age limit of 18 years.
 

• ECOG performance status 0 or 1 at screening.
 

• Ability to understand the nature of this study, comply with protocol requirements,
and give written informed consent. For minors, legal guardian willingness to give
written informed consent with patient assent, where appropriate.
 

• Patients of reproductive potential: All female study participants of reproductive
potential must have a negative serum or urine pregnancy test performed within 48
hours before study entry.
 
 Exclusion Criteria:
 
 The following key exclusion criteria apply:
 

• Patients with indolent Follicular Lymphoma or Chronic/Small/Prolymphocytic/Mantle
B-cell non-Hodgkin lymphoma in need of immediate cytoreductive therapy are excluded,
unless the patient has no remaining treatment choice with potential benefit.
 

• Patient has participated in any investigational research study and is being screened
for participation within a period of 5 half-lives, or 4 weeks of the last dose of
the investigational therapy, whichever is longer.
 

• Patients with history of severe hypersensitivity reactions to anti-CD20 treatment or
any components of study drug formulation.
 

• Presence or recent history within 6 months of arteritis or any systemic clotting
disorder, thrombotic or thromboembolic events.
 

• History or presence of autoimmune conditions; patients who have a medical condition
that requires chronic systemic steroid therapy or requires any other form of
immunosuppressive medication.
 

• Patients with a marked baseline prolongation of QT/QTc interval (e.g., repeated
demonstration of a QTc interval >480 milliseconds (ms) (CTCAE grade 1) using
Fredericia's QT correction formula.
 

• Active or latent hepatitis B or active hepatitis C or any uncontrolled infection at
screening; HIV positive test within 8 weeks of screening.
 

• Serious active infection at the time of treatment, or another serious underlying
medical condition that would impair the ability of the patient to receive protocol
treatment.
 

• Presence of other active cancers, or history of treatment for invasive cancer ≤3
years.
 

• Patients who started erythropoietin or granulocyte colony-stimulating factor
 (G-CSF), pegfilgrastim, or filgrastim ≤4 weeks prior to the first dose of the study
drug.
 

• Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.
 

• Active CNS disease involvement; CNS directed radiation must be completed >8 weeks
prior to CPO107 infusion.
 

• Non-CNS site of radiation must be completed >2 weeks prior to CPO107 infusion.

• Pregnant or nursing (lactating) women

• And others