Trial Information

A Phase 1-2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Background:

- HA22 is a recombinant immunotoxin containing an Fv fragment of an anti-CD22 monoclonal
antibody and truncated Pseudomonas exotoxin.

- HA22 (CAT-8015) is a mutant form of BL22 which had activity, including complete
response (CR), in chemo resistant hairy cell leukemia (HCL) and had activity in chronic
lymphocytic leukemia (CLL). HA22 contains 3 amino acids mutations greatly improved
binding and cytotoxicity toward CD22+ malignant cells due to lower off-rate, and may
enable HA22 to better target the least sensitive CD22+ malignant cells.

Objectives:

- Primary: To determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) and
safety profile of CAT-8015 in subjects with relapsed or refractory advanced B-cell non
Hodgkin's lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL),
mantle cell lymphoma (MCL) and CLL.

The secondary objectives of this study are:

- To describe the preliminary efficacy profile of CAT-8015 in patients with relapsed or
refractory advanced B-cell NHL (DLBCL, FL, MCL) or CLL .

- Determine pharmacokinetics and immunogenicity of CAT-8015 in subjects with B-cell
malignancies and describe the relationship between treatment benefit and safety.

- To determine the % expression of CD22 on tumor lymphocytes in these patient populations
and to describe the relationship between treatment benefit and safety.

- To investigate the following clinical and laboratory parameters as potential predictors
of vascular leak syndrome (VLS): orthostatic blood pressure, albumin levels, weight
changes, edema, and pulmonary findings.

Eligibility

Histologically confirmed B-cell NHL (DLBCL, FL, MCL) and:

- Have relapsed or refractory disease after at least one prior regimen containing
rituximab, either alone or in combination.

- Have measurable disease (at least one lesion greater than or equal to 20 mm in one
dimension or greater than or equal to 15 mm in two dimensions by conventional or high
resolution [spiral] computed tomography (CT).

- Not be a candidate for, or opted not to receive, a hematopoietic stem cell (HSC) or
bone marrow (BM) transplant.

OR, confirmation of B-cell CLL, requiring treatment and:

- Have a characteristic immunophenotype by flow cytometry.

- Have relapsed or refractory disease after at least 2 prior lines of treatment, at least
1 of which must have contained rituximab.

- Not be a candidate for, or opted not to receive, an HSC or BM transplant.

Design (Subjects will be treated on two phases: dose escalation or 4-arm expansion):

Dose Escalation

CAT-8015 will be given as a 30-minute IV infusion at 20, 30, 40, 50, or 60 microg/kg on Days
1, 3, and 5 of every 28-day cycle. Subsequent dose levels with a 10 microg/kg increase from
the previous dose level are possible if an MTD or OBD is not reached by 60 microg/kg.

Arm Expansion

In the 4-arm expansion phase, subjects will be treated at the MTD or OBD as identified in
the dose-escalation phase.