American Society of Hematology Conference 2020 – STRO-001 – Abstract

To view the abstract on ASH click here, ASH Website Preliminary Results of an Ongoing Phase 1 Dose Escalation Study of the Novel Anti-CD74 Antibody Drug Conjugate (ADC), STRO-001, in Patients with B-cell Non-Hodgkin Lymphoma Nirav N. Shah 1 , Ahmad Mattour 2 , Leslie Popplewell 3 , Charalambos B. Andreadis 4 , Jason M. Melear 5 , Alexander I. Spira 6 , Jonah Shulman 7 , Sudhir Manda 8 , John M. Burke 9 , Saurabh Chhabra 1 , Jeff P. Sharman 10 , Amrita Y. Krishnan 3 , Nina D. Shah 4 , Clifford DiLea 11 , Jason Kuriakose 12 , Craig J.Berman 12 , Shannon L. Matheny 12 , John Paul Leonard 13 , Arturo Molina 12 . Medical College of Wisconsin, Milwaukee, WI 1 ; Henry Ford Health System, Detroit, MI 2 ; City of Hope, Duarte, CA 3 ; University of California, San Francisco, San Francisco, CA 4 ; Texas Oncology, Austin, TX 5 ; Virginia Cancer Specialists, Fairfax, VA 6 ; Icahn School of Medicine at Mount Sinai, New York, NY 7 , Arizona Oncology Associates, Tucson, AZ 8 ; Rocky Mountain Cancer Centers, Aurora, CO 9 ; Willamette Valley Cancer Institute and Research Center, Eugene, OR 10 ; Aclairo Pharmaceutical Development Group, Vienna, VA 11 ; Sutro Biopharma, South San Francisco, CA 12 ; Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 13 . Background: CD74 is highly expressed on B cell malignancies, including non-Hodgkin’s lymphoma (NHL). STRO-001, a novel CD74-targeting ADC was generated using cell-free protein synthesis and site-specific conjugation platform technologies. STRO-001 contains a potent maytansinoid warhead conjugated to two specific sites (drug-antibody ratio of 2) using a stable non-cleavable linker. This first-in-human Phase 1, open-label, multicenter, dose escalation study was designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-001 in adults with B-cell malignancies (NHL and multiple myeloma). Herein we report preliminary results from the B-cell NHL cohort. Methods: Patients with advanced, relapsed/refractory NHL are eligible for enrollment. STRO-001 is administered as a 60-minute IV infusion. STRO-001 was initially administered on Days 1 and 15 of a 28-day cycle. Starting at 0.91 mg/kg, STRO-001 was administered on Day 1 of a 3-week cycle. Treatment is administered until disease progression or unacceptable toxicity. The study employed a modified 3+3 design with an accelerated dose titration (N=1 per cohort until set specified AEs are observed) for initial dosing cohorts. Results: 18 patients with NHL have been treated at 9 dose levels: .05, .075, .15, .27, .43, .65, .91, 1.27 and 1.78 mg/kg. NHL subtypes include: 6 diffuse large B-cell lymphoma (DLBCL), 5 follicular lymphoma (FL), 2 mantle cell lymphoma (MCL), 2 marginal zone lymphoma, 1 Burkitt’s lymphoma, 1 composite DLBCL/FL and 1 composite DLBCL/CLL. Median age is 64.5 (range 21-82). Median ECOG performance status is 1 (range 0-2). Median number of prior therapies is 4 (range 1-12). Three patients received prior CAR-T therapy. Median number of STRO-001 doses administered is 2 (range 1-12). 17 patients have completed at least one cycle of STRO-001 and are evaluable for safety and toxicity for dose escalation recommendation. One patient at the 1.78 mg/kg dose level is currently completing Cycle 1 and not yet evaluable for DLT assessment. Most AEs are grade 1 or 2 (90%) with the most common grade 1-2 TEAEs of chills, fatigue, nausea, anemia, headache, pyrexia, infusion reaction, decreased appetite, and abdominal pain occurring in ≥ 20% of patients. There was one DLT in the NHL cohort, a grade 3 thromboembolic event at the 0.91 mg/kg dose level. 16 patients are evaluable for response. The preliminary clinical benefit/disease control rate for all patients is 25% (4/16) including 1 patient with complete response (CR) 2 with partial response (PR) and 1 with stable disease (Table). One patient with DLBCL treated at .075 mg/kg achieved a CR after 2 cycles (4 doses) and progressed after 12 doses (on study 24 weeks). A DLBCL patient treated at 0.65 mg/kg achieved a PR at Cycle 3 and progressed after 8 doses (on study 15 weeks). A DLBCL patient treated at 1.27 mg/kg who achieved a PR has received 10 cycles and remains on study after 27 weeks. Preliminary PK analysis of ADC shows exposure increased (Cmax from 0.39 to 19 µg/mL) and (AUC0-tlast from 0.6 to 71 h*µg/mL) as dose increased from 0.05 to 0.91 mg/kg. Summary/Conclusion: STRO-001 is the first ADC generated with novel cell-free protein synthesis technology and site-specific conjugation to be tested in the clinic. STRO-001 has been well-tolerated. No ocular or neuropathy toxicity signals have been observed and the MTD has not been reached. Preliminary anti-tumor activity has been observed in this heavily pre-treated patient population, including two DLBCL patients who had previously progressed after a CAR-T (Table). The study continues to enroll patients in dose escalation. Next planned dose levels are 2.5 mg/kg and 3.5 mg/kg. This study is registered with clinicaltrials.gov identifier NCT03424603. Dose Level mg/kg Demographics Prior Therapies Best Response Doses Received Duration of Treatment 0.075 82-year-old man with Stage III diffuse large B-cell lymphoma (DLBCL), non-GC type diagnosed in 2015 – CHOP-R, – Rituximab/lenalidomide – Bendamustine/rituximab – Obinituzumab + gemcitabine + oxaliplatin Complete response 12 24 weeks 0.65 64-year old man diagnosed with double-hit Stage IV DLBCL in August 2017 – CHOP-R x 1 and EPOCH x 6 (2017) – RICE with IT prophylaxis (2017/2018) – Rituximab and XRT (2018) – Rituximab, gemcitiabine + oxaloplatin with XRT (2018) – Yescarta (CAR-T) (May 2018) – Rituximab and lenalidomide (Nov 2018) Partial response 8 15 weeks 1.27 68-year old woman stage IV extratranodal DLBCL, non-GC diagnosed in Feb 2018 – R-CHOP – RICE x 2 – DHAP x 2 – CAR-T May 2019 – Lenalidomide Nov 2019 Partial response 10 27 weeks ongoing 1,78 36-year old man with stage IIIA follicular lymphoma – Flt3L-vaccine IT – Rituximab – IT Prevnar – polyICIC (TLR-3 agonist) – IT – Pembrolizumab Stable response 4 12 weeks Keywords: Diseases, Lymphoid Malignancies, Non-Hodgkin Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, DLBCL, B-Cell Lymphoma

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