RESULTS FROM ONGOING PHASE 1/2 TRIAL OF SL-401 IN PATIENTS WITH INTERMEDIATE OR HIGH RISK RELAPSED/REFRACTORY MYELOFIBROSIS
Author(s): ,
Naveen Pemmaraju
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Vikas Gupta
Affiliations:
Princess Margaret Cancer Centre,Toronto,Canada
,
Gary Schiller
Affiliations:
UCLA,Los Angeles,United States
,
Sangmin Lee
Affiliations:
Weill Cornell Medical Center,New York,United States
,
Abdulraheem Yacoub
Affiliations:
Kansas University Cancer Center,Westwood,United States
,
Haris Ali
Affiliations:
City of Hope,Duarte,United States
,
Moshe Talpaz
Affiliations:
University of Michigan Health System,Ann Arbor,United States
,
Megan Sardone
Affiliations:
Stemline Therapeutics,New York,United States
,
Halyna Wysowskyj
Affiliations:
Stemline Therapeutics,New York,United States
,
Shay Shemesh
Affiliations:
Stemline Therapeutics,New York,United States
,
Janice Chen
Affiliations:
Stemline Therapeutics,New York,United States
,
Chris Brooks
Affiliations:
Stemline Therapeutics,New York,United States
,
Trishna Goswami
Affiliations:
Stemline Therapeutics,New York,United States
,
Vanessa Dunn
Affiliations:
Stemline Therapeutics,New York,United States
,
Animesh Pardanani
Affiliations:
Mayo Clinic,Rochester,United States
,
Ayalew Tefferi
Affiliations:
Mayo Clinic,Rochester,United States
,
Srdan Verstovsek
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Joseph Khoury
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
Mrinal Patnaik
Affiliations:
Mayo Clinic,Rochester,United States
EHA Library. Pemmaraju N. 06/15/18; 215063; PF618
Naveen Pemmaraju
Naveen Pemmaraju
Contributions
Abstract

Abstract: PF618

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background
Myelofibrosis (MF) patients that have failed or are intolerant to JAK inhibitors (JAKi) have no standard treatment options. SL-401 is a novel targeted therapy directed to the interleukin-3 receptor-α (CD123), a target expressed on a variety of malignancies, including certain myeloproliferative neoplasms (MPNs) such as MF. CD123 is also expressed on plasmacytoid dendritic cells (pDCs), which can reside in the tumor microenvironment and may play a role in promoting growth of MPN and other malignancies. Accordingly, a therapy directed at CD123-expressing malignant cells and/or neighboring pDCs may offer a novel therapeutic approach. SL-401 demonstrates high levels of clinical activity against blastic plasmacytoid dendritic cell neoplasm (BPDCN), a CD123+ malignancy derived from pDCs, and is being evaluated in Phase 1/2 trials of other cancers.

Aims
Primary objectives include assessment of safety, determining optimal dose/regimen, and evaluating efficacy outcomes.

Methods
This multicenter, 2-stage Phase 1/2 trial is enrolling MF patients that were relapsed, refractory, or unable to tolerate JAKi. In the Stage 1 dose escalation cohort (completed), SL-401 was dosed as a daily IV infusion at 7, 9, and 12 mcg/kg/day, on days 1-3 every 21 days (cycle 1-4), every 28 days (cycles 5-7), and every 42 days (cycles 8+). In Stage 2 (ongoing), the optimal dose determined in Stage 1 (12 mcg/kg) is being employed.

Results
As of 2/1/18, 14 patients (pts) with MF were treated with SL-401 (n=6 as 2nd-line; n=8 as 3rd-line, and beyond; with JAKi being the most commonly administered prior therapy). Median age 69 yrs (range 55-81); 71% female. DIPPS Plus risk group was intermediate-1 in 7% (1/14), intermediate-2 in 57% (8/14), and high in 36% (5/14) of pts. Median platelet count 56K/uL (range 19-232). 79% (11/14) of pts had baseline platelets <100K/uL, of which 4 pts (29%) had platelets <50K/uL. 79% (11/14) of pts had baseline splenomegaly defined as 5 cm below costal margin (BCM) by physical exam. Most common treatment-related adverse events (TRAEs), all grades, were thrombocytopenia, hypoalbuminemia and dizziness (all 29%). Most common ≥grade 3 TRAEs were anemia (21%) and thrombocytopenia (14%). Capillary leak syndrome reported in 1 pt (7%; grade 3). 55% (6/11) of pts with baseline splenomegaly had spleen reductions 25% (range 29-100%), including 3 pts (27%) with spleen reductions 35%, by physical exam: baseline to best response of 5 to 0 cm (100%), 19 to 10 cm (47%), 35 to 19 cm (46%), 30 to 20 cm (33%), 17 to 12 cm (29%), and 14 to 10 cm (29%) BCM. 5 spleen reductions occurred in pts with platelets <100K/uL, including 1 pt with a platelet count <50K/uL (100% spleen reduction [5 to 0 cm]). 75% (9/12) of evaluable pts experienced reductions in total symptom score (TSS) (range: 25%>100%), of which 4 pts (33%) had >50% TSS reduction. Median overall survival has not been reached (median follow-up 6.5 mos; range 0.1-20.6+ mos).

Conclusion
Single agent SL-401 was well-tolerated and demonstrated spleen reductions and symptom improvement in relapsed/refractory MF pts, including in some pts with thrombocytopenia. Given CD123 expression on certain myeloid neoplastic cells and tumor microenvironmental pDCs, SL-401 may offer a novel targeted approach in MF. Enrollment continues, and updated safety and efficacy data will be presented. Registration-directed designs are being evaluated. Clinical trial information: NCT02268253.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Microenvironment, Myelofibrosis, Targeted therapy

Abstract: PF618

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background
Myelofibrosis (MF) patients that have failed or are intolerant to JAK inhibitors (JAKi) have no standard treatment options. SL-401 is a novel targeted therapy directed to the interleukin-3 receptor-α (CD123), a target expressed on a variety of malignancies, including certain myeloproliferative neoplasms (MPNs) such as MF. CD123 is also expressed on plasmacytoid dendritic cells (pDCs), which can reside in the tumor microenvironment and may play a role in promoting growth of MPN and other malignancies. Accordingly, a therapy directed at CD123-expressing malignant cells and/or neighboring pDCs may offer a novel therapeutic approach. SL-401 demonstrates high levels of clinical activity against blastic plasmacytoid dendritic cell neoplasm (BPDCN), a CD123+ malignancy derived from pDCs, and is being evaluated in Phase 1/2 trials of other cancers.

Aims
Primary objectives include assessment of safety, determining optimal dose/regimen, and evaluating efficacy outcomes.

Methods
This multicenter, 2-stage Phase 1/2 trial is enrolling MF patients that were relapsed, refractory, or unable to tolerate JAKi. In the Stage 1 dose escalation cohort (completed), SL-401 was dosed as a daily IV infusion at 7, 9, and 12 mcg/kg/day, on days 1-3 every 21 days (cycle 1-4), every 28 days (cycles 5-7), and every 42 days (cycles 8+). In Stage 2 (ongoing), the optimal dose determined in Stage 1 (12 mcg/kg) is being employed.

Results
As of 2/1/18, 14 patients (pts) with MF were treated with SL-401 (n=6 as 2nd-line; n=8 as 3rd-line, and beyond; with JAKi being the most commonly administered prior therapy). Median age 69 yrs (range 55-81); 71% female. DIPPS Plus risk group was intermediate-1 in 7% (1/14), intermediate-2 in 57% (8/14), and high in 36% (5/14) of pts. Median platelet count 56K/uL (range 19-232). 79% (11/14) of pts had baseline platelets <100K/uL, of which 4 pts (29%) had platelets <50K/uL. 79% (11/14) of pts had baseline splenomegaly defined as 5 cm below costal margin (BCM) by physical exam. Most common treatment-related adverse events (TRAEs), all grades, were thrombocytopenia, hypoalbuminemia and dizziness (all 29%). Most common ≥grade 3 TRAEs were anemia (21%) and thrombocytopenia (14%). Capillary leak syndrome reported in 1 pt (7%; grade 3). 55% (6/11) of pts with baseline splenomegaly had spleen reductions 25% (range 29-100%), including 3 pts (27%) with spleen reductions 35%, by physical exam: baseline to best response of 5 to 0 cm (100%), 19 to 10 cm (47%), 35 to 19 cm (46%), 30 to 20 cm (33%), 17 to 12 cm (29%), and 14 to 10 cm (29%) BCM. 5 spleen reductions occurred in pts with platelets <100K/uL, including 1 pt with a platelet count <50K/uL (100% spleen reduction [5 to 0 cm]). 75% (9/12) of evaluable pts experienced reductions in total symptom score (TSS) (range: 25%>100%), of which 4 pts (33%) had >50% TSS reduction. Median overall survival has not been reached (median follow-up 6.5 mos; range 0.1-20.6+ mos).

Conclusion
Single agent SL-401 was well-tolerated and demonstrated spleen reductions and symptom improvement in relapsed/refractory MF pts, including in some pts with thrombocytopenia. Given CD123 expression on certain myeloid neoplastic cells and tumor microenvironmental pDCs, SL-401 may offer a novel targeted approach in MF. Enrollment continues, and updated safety and efficacy data will be presented. Registration-directed designs are being evaluated. Clinical trial information: NCT02268253.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Microenvironment, Myelofibrosis, Targeted therapy

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