53 subjects were randomized (27 placebo, 26 rusfertide) and completed part 2. 

Demographics: Median age 58 yr (range, 27-77); 37 men (71.7%) 15 women (28.3%); concurrent therapy: PHL alone 29 (54.7%) PHL + CYTO 24 (45.3%). 

Rusfertide met its primary efficacy end point of response as defined by not needing phlebotomy within 12 weeks (69.2% vs 18.5% in the placebo arm; P = .0003). Subgroup analysis showed superior efficacy for rusfertide relative to placebo in both concurrent therapy groups: TP alone (p=0.02) and TP+CYTO (p=0.02). 

Rusfertide significantly improved maintenance of response, absence of the need for TP and persistent HCT control compared to placebo (p<0.0001). 

In Part 1 the phlebotomy-free rate was 76.9% (wk 1-17) and 87.3% (wk 17-29). 

In Part 2, the rate was 92.3% for rusfertide cohort. 

Rusfertide was generally well tolerated; 83% of treatment-emergent adverse events (TEAEs) were grade 1-2, 17% were grade 3 with none grade 4 or 5. 

Most common TEAEs were injection site reactions (ISRs), which were localized, and grade 1-2 in severity. ISRs decreased in incidence with continued treatment. Only 2 TEAEs led to treatment discontinuation. 

Of the 70 patients enrolled, 52 (74.3%) have been treated for ≥1 year, 32 (45.7%) for ≥1.5 years, and 10 (14.3%) for ≥2 years, indicating long-term tolerability of rusfertide.

Rusfertide demonstrated favorable effects on several patient-reported outcomes, such as fatigue, problems with concentration, pruritus, and inactivity, and that was particularly seen in patients who had more severe symptoms at baseline.

The study included: screened 620, registered 488, and randomized 356 pts. 

By intention-to-treat analysis, RFS was higher for pts randomized to gilteritinib, but the difference was not statistically significant (HR: 0.679; 95% CI: 0.459, 1.005; 2-sided p-value: 0.0518). 

OS was similar in both groups (HR: 0.846; 95% CI: 0.554, 1.293; 2-sided p-value: 0.4394. 

Two-year RFS was 77.2% (95% CI 70.1%, 82.8%) for gilteritinib and 69.9% (95% CI: 62.4%, 76.2%) for placebo. 50.6% of pts had MRD (10-6 or greater) pre-HCT or pre-randomization. 

In pre-specified subgroup analysis, the effect of gilteritinib was more pronounced in pts with detectable MRD (HR=0.515, 95% CI: 0.316, 0.838, p = 0.0065) than in pts without detectable MRD (HR=1.213, 95% CI: 0.616, 2.387, p = 0.575). 143 (80.3%) in gilteritinib arm and 129 (72.9%) in placebo arm experienced dose interruptions and 97 (54.5%) in gilteritinib arm and 45 (25.4%) in placebo arm required dose reductions. 

No new safety signals were observed, with the most common being nausea and differentiation syndrome, and there was encouraging clinical activity, with about one-third of participants achieving complete remission and a 45% overall response rate.

Treatment-emergent adverse events (TEAE), including neutrophil decrease (42.1 versus 15.8%) and chronic GVHD (52.2 versus 42.1%), were more common in the gilteritinib arm, as were TEAEs leading to withdrawal of treatment.

Sixty-one participants were randomized (23 in 400mg CVP, 26 in 200 mg CVP, and 12 in PBO, respectively). 

Participants had severe ITP (median baseline PLT of 8,500/μL) and 68.3% of the participants had received ≥3 previous lines of therapies. 

Cevidoplenib was associated with a numerically greater rate of platelet response vs placebo (400 mg: 63.6%; 200 mg: 46.2%; placebo: 33.3%), but the difference was not statistically significant for either dose. Patients who sustained their platelet count, defined as having counts above 50,000 per μL at 4 or more of their last 6 visits, made up 27.3% of the 400 mg arm and 19.2% of the 200 mg arm; no patients in the placebo arm achieved this outcome.

Participants achieving 2 or more consecutive PLT counts ≥50,000/μL without the use of rescue medication were 40.9% on 400 mg CVP, 19.2% on 200 mg CVP vs. 8.3% on PBO (P=0.055 and P=0.371 for 400 mg and 200 mg CVP, respectively, vs. PBO). 

Sustained PLT count (defined retrospectively as PLT counts ≥50,000/μL at ≥4 of the last 6 visits) was reached in 27.3% on 400 mg CVP and 19.2% on 200 mg CVP vs. 0% on PBO. 

Mean change from baseline in the average of the last 2 available PLT counts (SD) were 41,600/μL (46,586) on 400 mg CVP, 36,020/μL (50,270) on 200mg CVP and 17,500/μL (26,821) on PBO. 

Platelet responses to cevidoplenib were consistent regardless of prior TRO-RAs use or baseline PLT counts <15,000/μL. 

Adverse events (AEs) were reported in 66.7% in the combined CVP groups (32 out of 48 participants treated with cevidoplenib) and 66.7% in the PBO group (8 out of 12 participants). The most frequently reported treatment related adverse events were ALT increase (8.3%), AST increase (6.3%) and nausea (4.2%). Most AEs were grade 1 or 2. Serious AEs were reported in 4.2% of the combined CVP group and 25% in the PBO. 

Treatment related grade 3 or 4 AEs were observed in 6.3% participants in the combined CVP group and resolved spontaneously or with medical management. No death was observed.

Median age of RP2D pts was 70.5 years (22 to 86y). 

FLT3 (30%) and IDH1/2 (40%) co-mutations were common (20% had both co-mutations). 

Median number of prior therapies was 3.0 (r: 1 to 10); 20% had ≥1 prior stem cell transplant (SCT). Based on updated results, the complete remission (CR) rate for NPM1m pts at 600mg is 35%, with 40% of pts overall achieving composite CR (CRc) and ORR of 45%. 

The median time to first response is 51 days (r: 26 to 225). One CR at the 200mg dose has an ongoing DoR of 35 cycles. The median DoR for all NPM1m pts achieving CRc is 8.2 months (m) per Kaplan-Meier estimate (95% CI: 1.0 to NE). 

Two pts (1 CR and 1 CRi) underwent SCT and remain in remission as of the cutoff, one on post-SCT ziftomenib maintenance therapy. Molecular analyses suggest ziftomenib leads to measurable residual disease (MRD) clearance of target mutations such as NPM1, and co-mutations (eg, FLT3 and IDH1) likely by targeting the founding clone and subclonal events or through targeting aberrant gene expression, as at least 2 pts with FLT3 and IDH1 co-mutations present at baseline were undetectable after 2 cycles. 

Most pts (85%) had at least one ≥Gr 3 treatment-emergent adverse event (TEAE); 30% were potentially treatment related. The most frequent (>20%) TEAEs ≥ Gr 3 were anemia (25%) and thrombocytopenia (20%). 

Any grade differentiation syndrome (DS) was reported in 20%; most (n=3) were Gr 2. The resistance profile was explored and the resistance mutation MEN1-M327I was found to develop in 1 of 29 pts (3.4%), detected at C4D28; the pt maintained stable disease through cycle 7. 

One key new biochemical finding, confirmed by crystal structure, demonstrates that ziftomenib retains full activity against the T349M mutation, detected in two thirds of pts who acquired menin gatekeeper mutations on another recent menin inhibitor trial.

Nine treatment-naïve patients (5 male, mean age 43 years [range 27–72], 7 requiring pre-study transfusions) have been treated with OMS906. Coexisting conditions include aplastic anemia (n=2), iron deficiency (n=5), myelodysplastic syndrome (n=2), and chronic renal failure (n=3). 

At baseline (N=9), mean Hgb and LDH were 6.78 g/dL and 1931 U/L. 8 patients have received 2 doses, 4 patients 3 doses, and 3 patients 5 doses. Four weeks after the first dose (n=8), mean Hgb increased by 3.43 g/dL (p=0.002) from a baseline of 6.33/6.20 g/dL (mean/median) and LDH fell by 1637 U/L (80%) (p<0.001) from a baseline of 2047/1573 U/L (mean/median). 

At the latest timepoint of 16 weeks (n=3), mean Hgb increase was 9.70 g/dL (p=0.017) from a baseline of 6.13/6.40 g/dL (mean/median) and LDH reduction was 87% (p=0.003) from a baseline of 2251/2375 U/L (mean/median). 

All patients (N=9) had an increase in Hgb >2 g/dL and all patients reaching 16 weeks have Hgb ≥15.7 g/dL. No patients required transfusions following OMS906 treatment. Mean absolute reticulocyte counts were reduced by 70,000/μL–136,000/μL at all timepoints. OMS906 was well tolerated. 

The most common adverse events were iron deficiency and transient neutropenia. No patients had clinical breakthrough hemolysis. Two patients had increases in LDH and bilirubin, suggesting initiation of hemolysis at the end of a dosing period, although Hgb was not reduced in either.

In terms of safety, it appeared to be well tolerated, with 2 patients reporting headache and 3 reporting itching, but there were no major TEAEs. Its efficacy also appeared promising, as all patients without myelodysplastic syndrome reached hemoglobin levels considered normal for their gender.