Abstracts of High Interest Highlighted by PETAL Investigators from the American Society of Hematology’s 2025 Annual Meeting
Abstracts of High Interest Highlighted by PETAL Investigators from the American Society of Hematology’s 2025 Annual Meeting
Abstracts of High Interest Highlighted by PETAL Investigators from the American Society of Hematology’s 2025 Annual Meeting
By Nathan Roberts, MD, Maya Srinivasan, MD, MS, and Mwanasha Merrill, MD
By Nathan Roberts, MD, Maya Srinivasan, MD, MS, and Mwanasha Merrill, MD
Initial clinical data from the Phase 1 study of DR-01, a non-fucosylated anti-CD94 antibody in patients with large granular lymphocytic leukemia
Initial clinical data from the Phase 1 study of DR-01, a non-fucosylated anti-CD94 antibody in patients with large granular lymphocytic leukemia
DR-01 is a first-in-human, non-fucosylated anti-CD94 monoclonal antibody designed to deplete pathogenic cytotoxic T-cell populations in large granular lymphocyte leukemia (LGLL) by enhancing antibody-dependent cellular cytotoxicity. CD94 is commonly expressed on the leukemic LGL clone.
This Phase 1/2 trial (NCT05475925) evaluates safety, tolerability, pharmacokinetics, and early efficacy in relapsed/refractory (R/R) LGLL patients. Patients were heavily pretreated, with most having prior to standard immunosuppressive therapies such as methotrexate, cyclophosphamide, or cyclosporine. Early safety findings from the first 31 enrolled patients show that DR-01 is generally well tolerated with no unexpected safety signals. Infusion-related reactions, occurring in 23% of patients, were among the most common adverse events; however, these were nearly all manageable with supportive care alone. Other common treatment-related adverse events included fatigue (16%) and nausea (16%) however the majority were Grade 1–2. No treatment-related deaths or dose-limiting toxicities were observed.
Preliminary efficacy was promising with early signs of hematologic improvement and responses (overall response rate [ORR] 44%, complete response [CR] rate 26% among 23 evaluable patients). Responses were typically observed early on with time to first response ranging from 0.9 to 1.8 months. These Phase 1 data suggest that DR-01 has an acceptable safety profile and preliminary clinical activity in R/R LGLL.
DR-01 is a first-in-human, non-fucosylated anti-CD94 monoclonal antibody designed to deplete pathogenic cytotoxic T-cell populations in large granular lymphocyte leukemia (LGLL) by enhancing antibody-dependent cellular cytotoxicity. CD94 is commonly expressed on the leukemic LGL clone.
This Phase 1/2 trial (NCT05475925) evaluates safety, tolerability, pharmacokinetics, and early efficacy in relapsed/refractory (R/R) LGLL patients. Patients were heavily pretreated, with most having prior to standard immunosuppressive therapies such as methotrexate, cyclophosphamide, or cyclosporine. Early safety findings from the first 31 enrolled patients show that DR-01 is generally well tolerated with no unexpected safety signals. Infusion-related reactions, occurring in 23% of patients, were among the most common adverse events; however, these were nearly all manageable with supportive care alone. Other common treatment-related adverse events included fatigue (16%) and nausea (16%) however the majority were Grade 1–2. No treatment-related deaths or dose-limiting toxicities were observed.
Preliminary efficacy was promising with early signs of hematologic improvement and responses (overall response rate [ORR] 44%, complete response [CR] rate 26% among 23 evaluable patients). Responses were typically observed early on with time to first response ranging from 0.9 to 1.8 months. These Phase 1 data suggest that DR-01 has an acceptable safety profile and preliminary clinical activity in R/R LGLL.
Clinical activity, tolerability, and pharmacodynamics of ulviprubart in patients with T-cell large granular lymphocytic leukemia: interim results of a Phase 1 trial
Clinical activity, tolerability, and pharmacodynamics of ulviprubart in patients with T-cell large granular lymphocytic leukemia: interim results of a Phase 1 trial
Ulviprubart (ABC008) is a first-in-class monoclonal antibody targeting KLRG1 that is designed to selectively deplete highly differentiated cytotoxic T cells that drive T-cell large granular lymphocytic leukemia (T-LGLL). This is a Phase 1/2 open-label, ascending dose clinical trial (NCT05532722) in patients with neutropenia and/or anemia due to T-LGLL. Early safety findings from the first 21 enrolled patients show that ulviprubart is well tolerated with only one treatment-related severe adverse event (infusion-related reaction) occurring and otherwise no discontinuations due to adverse events. Ulviprubart was effective at depleting pathogenic T-cell populations, with sustained reductions of >50% CD8+CD57+KLRG1+ T-cells in 54% of patients, including 23% of patients with >90% reduction of these target cells. Ulviprubart also showed promising clinical activity with ORR of 53% among patients with neutropenia and 22% among patients with anemia. The observed responses along with pharmacodynamic effects provide early evidence of clinical benefit, supporting continued development in this rare disease.
Together, these early phase clinical trials are clinically meaningful because they demonstrate the potential of targeted, clone-directed biologic therapies in LGLL rather than nonspecific immunosuppression. They mark a paradigm shift toward mechanism-based, disease-modifying therapy in LGLL, with the potential for greater efficacy, durability, and improved tolerability compared with current empiric approaches.
Ulviprubart (ABC008) is a first-in-class monoclonal antibody targeting KLRG1 that is designed to selectively deplete highly differentiated cytotoxic T cells that drive T-cell large granular lymphocytic leukemia (T-LGLL). This is a Phase 1/2 open-label, ascending dose clinical trial (NCT05532722) in patients with neutropenia and/or anemia due to T-LGLL. Early safety findings from the first 21 enrolled patients show that ulviprubart is well tolerated with only one treatment-related severe adverse event (infusion-related reaction) occurring and otherwise no discontinuations due to adverse events. Ulviprubart was effective at depleting pathogenic T-cell populations, with sustained reductions of >50% CD8+CD57+KLRG1+ T-cells in 54% of patients, including 23% of patients with >90% reduction of these target cells. Ulviprubart also showed promising clinical activity with ORR of 53% among patients with neutropenia and 22% among patients with anemia. The observed responses along with pharmacodynamic effects provide early evidence of clinical benefit, supporting continued development in this rare disease.
Together, these early phase clinical trials are clinically meaningful because they demonstrate the potential of targeted, clone-directed biologic therapies in LGLL rather than nonspecific immunosuppression. They mark a paradigm shift toward mechanism-based, disease-modifying therapy in LGLL, with the potential for greater efficacy, durability, and improved tolerability compared with current empiric approaches.
Interim analysis of safety and efficacy in a Phase 2 study of MB-105, a CD5.CAR T therapy for patients with R/R T-cell lymphoma
Interim analysis of safety and efficacy in a Phase 2 study of MB-105, a CD5.CAR T therapy for patients with R/R T-cell lymphoma
CAR-T therapy has emerged as one of the most compelling therapeutic advances in R/R peripheral T-cell lymphomas (PTCLs). Updated results from the Phase 2 MB-105 study demonstrated encouraging early efficacy of a CD5-directed CAR-T product engineered to resist fratricide via rapid CD5 degradation. Among patients with ≥50% CD5-expressing disease treated at the Phase 2 dose, 100% of evaluable patients responded (4/4) by investigator assessment, including 3 CR and 1 partial response (PR), despite a heavily pretreated population. Toxicity was manageable, with Grade 1 cytokine release syndrome in 50%, no neurotoxicity, and no prolonged ≥Grade 3 cytopenias supporting continued accrual in this multicenter study.
CAR-T therapy has emerged as one of the most compelling therapeutic advances in R/R peripheral T-cell lymphomas (PTCLs). Updated results from the Phase 2 MB-105 study demonstrated encouraging early efficacy of a CD5-directed CAR-T product engineered to resist fratricide via rapid CD5 degradation. Among patients with ≥50% CD5-expressing disease treated at the Phase 2 dose, 100% of evaluable patients responded (4/4) by investigator assessment, including 3 CR and 1 partial response (PR), despite a heavily pretreated population. Toxicity was manageable, with Grade 1 cytokine release syndrome in 50%, no neurotoxicity, and no prolonged ≥Grade 3 cytopenias supporting continued accrual in this multicenter study.
First‑in‑human Phase 1 dose‑finding study (VIPER 101) of dual‑population autologous CD5‑deleted anti-CD5 CAR‑T (Senza5 CART5) cells in R/R T‑cell lymphomas
First‑in‑human Phase 1 dose‑finding study (VIPER 101) of dual‑population autologous CD5‑deleted anti-CD5 CAR‑T (Senza5 CART5) cells in R/R T‑cell lymphomas
Complementary data from the first-in-human VIPER-101 trial of Senza5 CART5 highlighted an alternative CD5-targeting strategy using CRISPR-mediated CD5 deletion and a dual-population CAR-T product designed to mitigate T-cell aplasia. Among efficacy-evaluable patients, ORR was 100% (3/3), with all achieving complete remission, including patients with PTCL-not otherwise specified (NOS), T-follicular helper lymphoma, angioimmunoblastic T-cell lymphoma (AITL), and mycosis fungoides. CAR-T expansion was robust and durable, with tissue trafficking confirmed on biopsy and early immune reconstitution, with emergence of CD5-negative, CAR-negative T cells. While follow-up remains short, these studies collectively signal a meaningful inflection point for CAR-T therapy in PTCL, demonstrating that rational engineering can translate into high response rates with acceptable safety in a disease space with a high unmet need.
Complementary data from the first-in-human VIPER-101 trial of Senza5 CART5 highlighted an alternative CD5-targeting strategy using CRISPR-mediated CD5 deletion and a dual-population CAR-T product designed to mitigate T-cell aplasia. Among efficacy-evaluable patients, ORR was 100% (3/3), with all achieving complete remission, including patients with PTCL-not otherwise specified (NOS), T-follicular helper lymphoma, angioimmunoblastic T-cell lymphoma (AITL), and mycosis fungoides. CAR-T expansion was robust and durable, with tissue trafficking confirmed on biopsy and early immune reconstitution, with emergence of CD5-negative, CAR-negative T cells. While follow-up remains short, these studies collectively signal a meaningful inflection point for CAR-T therapy in PTCL, demonstrating that rational engineering can translate into high response rates with acceptable safety in a disease space with a high unmet need.
Final results of a Phase 1 trial with soquelitinib (SQL), a selective interleukin-2-inducible T cell kinase (ITK) inhibitor for treatment of R/R T-cell lymphomas (TCL)
Final results of a Phase 1 trial with soquelitinib (SQL), a selective interleukin-2-inducible T cell kinase (ITK) inhibitor for treatment of R/R T-cell lymphomas (TCL)
ITK expression in T cells and associated signaling pathways results in T-cell receptor activation and differentiation of T helper (Th) cells. Soquelitinib is a small molecule oral selective covalent inhibitor of ITK which results in a suppressed Th2 response with sparing of Th1 function and cytokine production. Given the role of TCR signaling in TCL, SQL is active in TCL due to direct effects on tumor cells and induction of anti-tumor immunity.
75 R/R TCL patients were enrolled in this Phase 1 study, with 28 patients in dose escalation and 48 patients in dose expansion. The cohort included 57% males, and 3 median prior therapies (range 1 to 19). Histology included PTCL-NOS (n=32), AITL (n=12), cutaneous T-cell lymphoma (n=19), and others (n=12). Sustained complete target occupancy was achieved with >200 mg BID.
At 200 mg BID of SQL, expansion and escalation cohorts resulted in durable and effective ORRs. An ORR of 39% (6/23) was achieved in patients who had 1–3 prior cytotoxic regimens including 6 durable CR (28, 25, 22+, 21, 17+, and 12 months), 3 PR (29+, 7, and 7 months) across a range of histologies. However, ORR was 0% in 14 patients with >3 prior lines of therapies. 11 patients were tested for GATA3+ by IHC (H score>100), associated with poorer response, 6 of which were PTCL-NOS and 2 achieved CR. Th1 effector cells increased in blood and decreased in Th17 as well as decreased IL-5. Median PFS was 6.2 months with a median overall survival of 28.1 months. There were no dose-limiting toxicities, and 29% of patients had Grade 3+ adverse events, with the most common being pruritus and anemia, which were unrelated to the drug.
ITK expression in T cells and associated signaling pathways results in T-cell receptor activation and differentiation of T helper (Th) cells. Soquelitinib is a small molecule oral selective covalent inhibitor of ITK which results in a suppressed Th2 response with sparing of Th1 function and cytokine production. Given the role of TCR signaling in TCL, SQL is active in TCL due to direct effects on tumor cells and induction of anti-tumor immunity.
75 R/R TCL patients were enrolled in this Phase 1 study, with 28 patients in dose escalation and 48 patients in dose expansion. The cohort included 57% males, and 3 median prior therapies (range 1 to 19). Histology included PTCL-NOS (n=32), AITL (n=12), cutaneous T-cell lymphoma (n=19), and others (n=12). Sustained complete target occupancy was achieved with >200 mg BID.
At 200 mg BID of SQL, expansion and escalation cohorts resulted in durable and effective ORRs. An ORR of 39% (6/23) was achieved in patients who had 1–3 prior cytotoxic regimens including 6 durable CR (28, 25, 22+, 21, 17+, and 12 months), 3 PR (29+, 7, and 7 months) across a range of histologies. However, ORR was 0% in 14 patients with >3 prior lines of therapies. 11 patients were tested for GATA3+ by IHC (H score>100), associated with poorer response, 6 of which were PTCL-NOS and 2 achieved CR. Th1 effector cells increased in blood and decreased in Th17 as well as decreased IL-5. Median PFS was 6.2 months with a median overall survival of 28.1 months. There were no dose-limiting toxicities, and 29% of patients had Grade 3+ adverse events, with the most common being pruritus and anemia, which were unrelated to the drug.
For Healthcare Professionals
@2025 PETAL Consortium • All rights reserved
For Healthcare Professionals
@2025 PETAL Consortium • All rights reserved
For Healthcare Professionals
@2025 PETAL Consortium • All rights reserved