Background: Sutro’s cell-free antibody production system was used to generate STRO-001, a novel CD74 targeting antibody drug conjugate. CD74 is expressed on B cells throughout differentiation and is an attractive target for treatment of B cell malignancies (Zhao et al, J Path Clin Res, Jan 2019). STRO-001 demonstrates potent cytotoxicity in non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) cell lines and anti-tumor activity in xenograft models. Toxicology studies demonstrate dose-dependent B-cell depletion and reversible hematologic toxicity when STRO-001 is administered at up to 10 mg/kg (Solis et al, Proc AACR 2018, Abs 742).

Methods: This study (NCT03424603) is a first-in-human Phase 1, open-label, multicenter, dose escalation (Part 1) study with dose expansion (Part 2) to identify the maximum tolerated dose (MTD), recommended phase 2 doses (RP2D) and to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-001 in adults with B-cell malignancies (MM and NHL) who are refractory to, or intolerant of, all therapy known to provide clinical benefit. STRO-001 is given to all patients on study via intravenous infusion on Day 1 and Day 15 of each cycle until disease progression. Dose limiting toxicities are assessed in the first cycle (Days 1-28) of dose escalation. In Part 1, 2 cohorts (1 for MM and 1 for NHL) will enroll 30 patients each to determine the MTD and RP2D for expansion while Part 2 will enroll 4 dose expansion cohorts based on disease subtypes (MM, diffuse large B cell, mantle cell and follicular lymphomas). Efficacy will be evaluated per MM-specific or NHL-specific criteria. Key inclusion criteria include relapsed or relapsed/refractory disease, adequate bone marrow and renal function, and ability to comply with treatment, testing and pharmacokinetic (PK) schedules. NHL patients must have at least one measurable lesion. Key exclusion criteria include leukemic manifestations of lymphoma, need for ongoing anti-coagulants or immunotherapy including systemic corticosteroids and a history of CNS involvement. Samples will be collected to assess the PK and immunogenicity. No formal statistical hypothesis testing will be conducted in this study. This study is currently open for enrollment in the US at the following sites: Medical College of Wisconsin, City of Hope, UCSF, Rocky Mountain Cancer Centers, Texas Oncology, Virginia Cancer Specialists, Winship Cancer Institute of Emory University, and the Willamette Valley Cancer Institute and Research Center.

Citation Format: Nirav N. Shah, Amrita Y. Krishnan, Nina D. Shah, John M. Burke, Jason M. Melear, Alexander I. Spira, Jonathan L. Kaufman, Jonathon B. Cohen, Ruben Niesvizky, Leslie L. Popplewell, Saurabh Chhabra, Jeff P. Sharman, Thomas G. Martin, Shannon L. Matheny, John P. Leonard, Arturo Molina. A Phase I open-label, safety, pharmacokinetic, and preliminary efficacy study of STRO-001, an anti-CD74 antibody drug conjugate, in patients with advanced B-cell malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT104.