Updated clinical data and biomarker analyses from the phase 1 study of DR-01, a non-fucosylated anti-CD94 antibody in patients with relapsed/refractory cytotoxic lymphomas

Abstract

Abstract Introduction: DR-01 is a non-fucosylated human IgG antibody targeting CD94, expressed on terminal effector CD8+T cells, γδT cells, and NK cells leading to depletion of CD94-expressing malignant cells by antibody-dependent cellular cytotoxicity including fratricide. Patients with relapsed/refractory (RR) cytotoxic T cell lymphomas (CTLs) have no established effective treatment options. This Phase 1/2 open-label, dose-escalation and expansion study (NCT05475925) is assessing DR-01 safety, pharmacokinetics (PK), pharmacodynamics and initial efficacy and in R/R CTL patients.As previously presented, DR-01 demonstrated promising safety and efficacy (Iyer 2025). Preliminary data on CD94 expression in CTL, and the predictive value of this data with respect to DR-01 treatment response, is presented. Methods : CTL patients who failed ≥1 prior line of therapy were enrolled. Dose escalation (0.3-10 mg/kg) was followed by expansion at 1 or 6 mg/kg with induction regimens of C1D1/D15 or C1D1/D8/D15. For biomarker analyses, an immunohistochemistry (IHC) method for CD94 was developed and validated for exploratory use with FFPE tissue using a non-competing CD94 antibody. Tumor biopsies were collected from patients (pts) enrolled in the study at baseline, C2D1 and/or at progression for analysis. Tissue samples from the clinical study and from external sources [Samsung Medical Center and Stanford] were evaluated for CD94 expression by IHC at a centralized testing laboratory using the validated method. Stained slides were reviewed by a certified pathologist and H-scoring was used to semi-quantify CD94 expression on mononuclear cells. Preliminary correlation analyses were performed to elucidate the relationship between CD94 expression and clinical outcome in CTL patients receiving DR-01. Results As of May 2025, 64 pts with CTL (37 males) were enrolled. The median age was 53 years (range 18–82) with a median of 3 prior lines of therapy (range 1–14). Thirty-five pts (55%) were White, 6 (9.4%) Black, and 12 (19%) Asian, remaining pts were other or unknown; 9 (14%) reported Hispanic ethnicity. ECOG scores were evenly distributed between 0 and 1. Disease was resistant or intolerant to most recent therapy in 50% (n=32) of pts and relapsed post autologous or allogeneic hematopoietic stem cell transplant in 19% (n=12). Infusion-related reactions were the predominant treatment-related adverse events (TRAEs), occurring in 34% of pts (n=22; including 2 Grade 3 events), primarily during initial administration and managed effectively with standard mitigation measures. At the selected dose of 1 mg/kg (n=28), the ORR was 54% (8 CR, 7 PR), with the longest duration of response ongoing at 16 months. Responses were seen across majority of histologic subtypes. Of 35 baseline CTL samples from the study and 48 specimens from external sources, 82 out of 83 (98.8%) were CD94-positive by IHC. Staining was localized to mononuclear cells and was primarily membranous in location. In the CTL subtypes evaluated to date, median (interquartile range, IQR) H-scores were 205 (123) for extranodal NK T-cell lymphoma (n=25), 75 (53) for subcutaneous panniculitis-like T-cell lymphoma (n=15), 125 (249) for primary cutaneous γδ T-cell lymphoma (n=14), 33 (129) for primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (n=9) and 43 (153) for other subtypes (n=20) including PTCL-NOS (CD8+, γδ+ phenotype), primary cutaneous PTCL-NOS. These data are consistent with literature, which also demonstrate high CD94 expression across various histological subtypes of CTL. CD94 expression in CTL specimens highly correlated with granzyme B expression emphasizing its association with cytotoxic NK/T cell populations (n=42, r=0.54, p=0.0002). Among 10 patients with serial biopsies, a reduction in CD94 H-score (relative to baseline) indicative of tumor cell depletion was observed at C2D1 in 9 patients across all DR-01 dose levels ≥1 mg/kg. Responses were seen in patients with a wide range of baseline CD94 expression (H-score range of 15-295). Conclusions DR-01 continues to demonstrate promising safety and efficacy, supporting its development as a potential treatment option for CTL. Biomarker analyses show that CD94 is widely expressed across most CTL. Notably, the preliminary data suggest that patients with CTL may benefit from DR-01 regardless of baseline positive CD94 expression by IHC.