Study of STRO-001, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies

Study Overview
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Brief Summary
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First-in-human Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-001 given intravenously every 3 weeks.

Detailed Description
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This study is a first-in-human Phase 1, open-label, multicenter, dose escalation study with dose expansion to identify the maximum tolerated dose (MTD), the recommended phase 2 doses (RP2D) and to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-001 in adult subjects with B-cell malignancies (MM and NHL) who are refractory to, or intolerant of, all established therapy known to provide clinical benefit for their condition (i.e., trial subjects must not be candidates for any regimens known to provide clinical benefit). The study will consist of two parts: Part 1, dose escalation, and Part 2, dose expansion. The study uses an accelerated dose titration design for dose escalation. Doses will be escalated using an N-of-1 per dosing cohort until the first instance of a treatment-related, clinically relevant Grade 2 non-hematologic toxicity or a Grade 3 hematologic toxicity of any type is observed during Cycle 1 (first 21 days). Following this a standard 3+3 trial design is used for all further escalation cohorts. Dose escalation is conducted independently for the two dose escalation tumor cohorts (MM and NHL). A recommended STRO-001 dose for expansion will be determined for MM and NHL. The dose expansion (Part 2) portion of the study will begin when Part 1 is completed. Enrollment in dose expansion will include separate tumor cohorts of MM and NHL. In both Part 1 and Part 2 of the study, STRO-001 will be dosed as an intravenous (IV) infusion on Day 1 of a 21-day cycle, until disease progression. Labs will be drawn on a weekly basis for Cycles 1-4, and every three weeks starting with Cycle 5. Weekly clinical evaluations will be conducted during the first 4 cycles; thereafter, clinical evaluations will be conducted on infusion days (Day 1 of each cycle). Samples for pharmacokinetics (PK) analysis will occur at specific times on Days 1, 2, and 8 of the first two cycles of treatment, Day 1 of the third cycle of treatment and at End of Treatment visit. Additional clinical evaluations and labs may occur at the discretion of the investigator. Subjects who receive any dose of STRO-001 will be included in safety analyses. Disease evaluations will include peripheral blood analysis, bone marrow assessments and scans as appropriate. Disease status will be evaluated per MM-specific or NHL-specific criteria. Samples will be collected to assess the PK and immunogenicity of STRO-001. Biomarkers may be assessed from bone marrow, peripheral blood and/or tissue samples. Subjects will continue to receive study drug until disease progression, unacceptable toxicity, withdrawal of consent, or end of study (study completion).

Official Title
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A Phase 1 Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of STRO-001, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies

Conditions
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B-cell Lymphoma, Non Hodgkin Lymphoma, Multiple Myeloma, Follicular Lymphoma, Mantle Cell Lymphoma, Diffuse Large B Cell Lymphoma, Indolent Lymphoma, B Cells--Tumors

Intervention / Treatment
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* Drug: STRO-001


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Confirmation of diagnosis Relapsed or relapsed/refractory disease Age ≥ 18 years ECOG performance status (0-2) Life expectancy > 3 months Adequate bone marrow and renal functions QTcF <500 msec Ability to comply with treatment, PK and test schedules NHL only- at least one measurable lesion Key Exclusion Criteria: Active plasma cell leukemia and/or leukemic manifestations of lymphoma Known amyloidosis (MM patients) Chronic lymphocytic leukemia and Richter's transformation, and prolymphocytic leukemia (NHL subjects) T-cell malignancy Sensory or motor neuropathy ≥ grade 2 Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis C Ongoing immunosuppressive therapy, including systemic corticosteroids. Note: Subjects may be using topical or inhaled corticosteroids. Clinically significant cardiac disease Significant concurrent, uncontrolled medical condition History or clinical signs of meningeal or active CNS involvement Known severe chronic obstructive pulmonary disease or asthma History of significant cerebrovascular disease Known Human Immunodeficiency Virus seropositivity Positive serology for hepatitis B defined by a positive test for HBsAg Concurrent participation in another therapeutic treatment trial High screening liver function tests Prior treatment with CD74 targeting therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STRO-001<br>intravenous | Drug: STRO-001<br>* intravenous antibody drug conjugate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001) | Incidence of adverse events (AEs) observed across STRO-001 dose levels | 18 months | 
| Part 1: Define the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of STRO-001 | Frequency of dose-limiting toxicity and exposure across STRO-001 dose levels | 18 months | 
| Part 2: Evaluate preliminary anti-tumor activity (multiple myeloma patients) | Objective response rates per International Myeloma Working Group (IMWG) criteria for response assessment | 24 months | 
| Part 2: Evaluate preliminary anti-tumor activity (NHL patients) | Objective response rates per the Lugano classification for response assessment | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Characterize the pharmacokinetics (PK) of STRO-001 by measuring the maximum plasma concentration (Cmax) | Measurement of maximum plasma concentration after the administration of STRO-001 | 18 months | 
| Part 1: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001 | Measurement of terminal half-life of STRO-001 after the administration of STRO-001 | 18 months | 
| Part 1: Characterize the PK of STRO-001 measuring the total area under the concentration versus time curve from zero to infinity (AUCinf) | Measurement of AUC to infinity (AUCinf) | 18 months | 
| Part 1: Characterize the PK of STRO-001 by measuring the clearance (CL) | Measurement of total body clearance | 18 months | 
| Part 1: Characterize the PK of STRO-001 by measuring the the steady state volume of distribution (Vss) | Measurement of steady state volume of distribution | 18 months | 
| Part 1: Assess the immunogenic potential of STRO-001 | Evaluation and quantitation of circulating anti-drug antibodies (ADAs) over time | 18 months | 
| Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001) | Number of patients with abnormal laboratory values and/or adverse events related to STRO-001 treatment | 24 months | 
| Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of duration of response (DOR) in patients treated with STRO-001 | Each cohort will be analyzed independently | 24 months | 
| Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of progression-free survival (PFS) in patients treated with STRO-001 | Each cohort will be analyzed independently | 24 months | 
| Part 2: Characterize the PK of STRO-001 by measuring the maximum plasma concentration (Cmax) | Measurement of maximum plasma concentration after the administration of STRO-001 | 24 months | 
| Part 2: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001 | Measurement of terminal half-life of STRO-001 after the administration of STRO-001 | 24 months | 
| Part 2: Characterize the PK of STRO-001 by measuring the area under the plasma concentration versus time curve (AUC) | Measurement of AUC to infinity (AUC inf) | 24 months | 
| Part 2: Characterize the PK of STRO-001 by measuring the clearance (CL) | Measurement of total body clearance | 24 months |