STRO-001, an antibody-drug conjugate (ADC) targeting CD74, is showing early promise in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Preliminary results from an ongoing Phase 1 dose-escalation study were presented, highlighting the drug's tolerability and initial anti-tumor activity in a heavily pre-treated patient population.
The open-label, multicenter study is evaluating the safety, tolerability, and preliminary efficacy of STRO-001 in adults with B-cell malignancies. The data presented focused on the NHL cohort. STRO-001, created using cell-free protein synthesis and site-specific conjugation, consists of a potent maytansinoid warhead attached to the anti-CD74 antibody at a drug-antibody ratio of 2 via a stable, non-cleavable linker.
Study Design and Patient Population
Eligible patients had advanced, relapsed/refractory NHL and received STRO-001 as a 60-minute IV infusion. The treatment schedule initially involved administration on Days 1 and 15 of a 28-day cycle, but later shifted to Day 1 of a 3-week cycle, starting at 0.91 mg/kg. Treatment continued until disease progression or unacceptable toxicity. The study utilized a modified 3+3 design with accelerated dose titration.
Eighteen NHL patients were treated across nine dose levels, ranging from 0.05 to 1.78 mg/kg. The NHL subtypes included diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma, Burkitt’s lymphoma, and composite lymphomas. The median age was 64.5 years, the median ECOG performance status was 1, and the median number of prior therapies was 4. Three patients had previously received CAR-T therapy. The median number of STRO-001 doses administered was 2.
Safety and Tolerability
Seventeen patients were evaluable for safety and toxicity. The majority of adverse events (AEs) were grade 1 or 2 (90%), with common AEs including chills, fatigue, nausea, anemia, headache, pyrexia, infusion reaction, decreased appetite, and abdominal pain. One dose-limiting toxicity (DLT), a grade 3 thromboembolic event, occurred at the 0.91 mg/kg dose level. Notably, no ocular or neuropathy toxicity signals were observed.
Efficacy
Sixteen patients were evaluable for response. The preliminary clinical benefit/disease control rate was 25% (4/16), with one complete response (CR), two partial responses (PR), and one stable disease. A DLBCL patient treated at 0.075 mg/kg achieved a CR after 2 cycles but progressed after 12 doses. A DLBCL patient treated at 0.65 mg/kg achieved a PR at Cycle 3 and progressed after 8 doses. A DLBCL patient treated at 1.27 mg/kg achieved a PR and remained on study after 27 weeks.
Pharmacokinetics
Preliminary pharmacokinetic (PK) analysis showed that ADC exposure increased with dose escalation, with Cmax increasing from 0.39 to 19 µg/mL and AUC0-tlast increasing from 0.6 to 71 h*µg/mL as the dose increased from 0.05 to 0.91 mg/kg.
Ongoing Development
STRO-001 is the first ADC generated with novel cell-free protein synthesis technology and site-specific conjugation to be tested in the clinic. The study is ongoing, with plans to enroll patients at higher dose levels of 2.5 mg/kg and 3.5 mg/kg. The trial is registered with clinicaltrials.gov identifier NCT03424603.
