Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Methods:We conducted a multicenter, phase 1/2 trial (CTR20201950) at 17 sites in China. This study included dose-escalation cohort (phase 1) and dose-expansion cohort (phase 2). Aged ≥18 with MF, international prognostic scoring system (IPSS) intermediate- 1/2 or higher risk of MF were enrolled. Eligible pts received escalating doses of oral OB756 at 4 dose cohorts ranging from 8 to 32 mg of each 28-day cycle, and a modified “3 + 3” design was used in phase 1. In phase 2 study, patients (pts) were treated with OB756 with RP2D of 16mg or 20mg twice daily for 28-day cycles until progressive disease or intolerance. The primary endpoints were the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in phase 1, and the proportion of pts with ≥35% spleen volume reduction (SVR35) from baseline at week 24 in phase 2. The main secondary endpoint included symptom response (≥50% reduction in total symptom score, TSS50) from baseline at week 24, platelet and anemia improvement, and safety in phase 2.
Results:Between November 3, 2020 and May 16, 2024, 296 pts were assessed for eligibility, 75 pts of MF were enrolled and treated with OB756 including, 9 pts in phase 1 and 66 pts in phase 2. In phase 1, the number of pts enrolled per dose level was one at 8 mg BID, three at 16 mg BID, four at 24 mg BID, and one at 32 mg BID. No pts experienced dose-limiting toxicities (DLTs) of OB756 form 8 to 32mg BID. Given the safety profile and shrinking spleen, 16 mg BID and 20mg BID was identified as RP2D according to p-STAT3 inhibited percentage in Imax model. In phase 2, median age was 58 (range, 55-69) years. 47/66 (71.2%) pts had a diagnosis of PMF, 14/66 (21.2%) post-PV MF, and 5/66 (7.6%) post-ET MF, with IPSS assessment of intermediate-1 risk in 19/66 (28.8%) pts, intermediate-2 risk in 27/66 (40.9%) pts, and high risk in 21/66 (31.8%) pts. Baseline median spleen volume was 1780.2 (rang, 1132.5~2728.7) ml. Pts identified JAK2 V617F, CALR and MPL mutation were 87.1% (57/66), 12.1% (7/66), 1.6% (1/66), respectively. A total of 36/66 (54.5%) pts achieved SVR35 at EOC6, especially with 7/25 (28%) pts quickly shrinked spleen more than 5cm from baseline at week 1. In addition, pts had SVR35 during study period and EOC12 were 39/66 (59.1%), 12/24 (50.0%), respectively. In secondary endpoints, 31/55 (51.4%), 34/53 (64.2%), and 7/8 (87.5%) pts achieved TSS50 at EOC3, EOC6, and EOC20, respectively. OB756 had quick spleen reduction and durable SVR. OB756 treatment increased hemoglobin level to ≥20 g/L in 15.0% (3/20) of pts with hemoglobin ≤100 g/L at baseline. The most common treatment-emergent adverse events (TEAEs) were 1~2 grade. Only three commonly non-hematological TEAEs (incidence ≥10%) were reported with serum creatinine increased (12/66, 18.2%), aspartate aminotransferase increased (13/66, 29.7%), gamma-glutamyl transferase increased (7/66,10.6%). The most common grade≥3 hematological TEAE (≥10%) were thrombocytopenia (15/66, 22.7%) and anemia (23/66, 34.8%). Occurrence of other grade≥3 non-hematologic TEAEs was very low. No death was reported with related to disease progression of MF or OB756. TEAEs were generally manageable.
Conclusion:OB756 is well tolerated and showed meaningful clinical activity in patients with MF, especially for quick and durable spleen reduction. OB756 also showed few non-hematological TEAEs, and may be a new treatment option for MF patients.
Disclosures: No relevant conflicts of interest to declare.
See more of: Oral and Poster Abstracts