Page 154 - Haematologica Vol. 109 - July 2024

ARTICLE - Sovleplenib Syk inhibitor in R/R B-cell tumors
Y. Song et al.
stage III or IV. The median time from diagnosis to first dose was 32.9 months (range, 5.4-104.3) (Online Supplementary Table S1). All patients had received previous anti-tumor treatment, with 13 (48.1%) having received ≥3 lines of treatment. Twenty-one (77.8%) patients had received pre- vious anti-CD20 antibody treatment. All patients received ≥1 dose of sovleplenib, as follows: 200 mg q.d. (N=7), 400 mg q.d. (N=3), 600 mg q.d. (N=6), 800 mg q.d. (N=3), 200 mg b.i.d. (N=8). At data cutoff (April 30, 2021), all patients had discontinued treatment, most of them discontinued because of PD (N=12; 44.4%).
Dose expansion
horts A (N=19), B (N=14), C (N=10) or D (N=64). The number of enrolled patients being less than the planned sample size was due to difficulties in enrolling patients with CLL/ SLL and indolent B-cell lymphoma. The median time from diagnosis to first dose was 37.3 months (range, 1.9-152.4) (Table 1). Of patients enrolled, 83 (77.6%) were classified as Ann Arbor stage III or IV. All patients received prior anti-tumor treatment, and 48 (44.9%) received ≥3 lines of treatment. Eighty-seven (81.3%) patients had received previous anti-CD20 antibody treatment. In cohort A, eight (42.1%) patients had received a prior BTKi, and two (10.5%) patients had a received prior BCL-2 inhibitor (Table 1). Oth- er baseline demographic and disease characteristics are presented in Online Supplementary Table S2. One (0.9%)
During dose expansion, 107 patients were enrolled in co-
Table 1. Baseline demographic and disease characteristics of the safety set in the dose-expansion phase.
Parameter
CLL/SLL N=19
Aggressive B-cell lymphomas N=14
MCL N=10
Indolent B-cell lymphoma N=64
Total N=107
Age in years, median (range)
57.0 (33-78)
65.0 (40-74)
65.0 (56-73)
57.0 (30-77)
58.0 (30-78)
Sex: male, N (%)
13 (68.4)
4 (28.6)
9 (90.0)
36 (56.3)
62 (57.9)
Baseline ECOG score, N (%) 01
7 (36.8) 12 (63.2)
5 (35.7) 9 (64.3)
4 (40.0) 6 (60.0)
29 (45.3) 35 (54.7)
45 (42.1) 62 (57.9)
Median time in months since diagnosis (range)
42.10 (4.1-152.4)
22.85 (3.8-107.2)
47.30 (15.3-135.5)
35.15 (1.9-152.2)
37.30 (1.9-152.4)
Time since last relapse or disease progression N of patients
Months, median (range)
17
1.05 (0.3-2.9)
12
1.05 (0.5-2.1)
9
1.91 (0.3-17.5)
59
1.31 (0.2-42.6)
97
1.28 (0.2-42.6)
Lines of last anti-tumor drug treatment, N (%) 1 line
2 lines ≥3 lines
4 (21.1) 6 (31.6) 9 (47.4)
4 (28.6) 1 (7.1) 9 (64.3)
2 (20.0) 3 (30.0) 5 (50.0)
22 (34.4) 17 (26.6) 25 (39.1)
32 (29.9) 27 (25.2) 48 (44.9)
Median time in months from last systemic therapy to sovleplenib treatment (range)
2.05 (1.0-58.3)
2.55 (1.0-28.2)
6.00 (1.2-63.8)
5.90 (1.0-50.8)
3.80 (1.0-63.8)
Prior anticancer agents, N (%)
19 (100)
14 (100)
10 (100)
64 (100)
107 (100)
Chemotherapy, N (%) Alkylating agents Anthracycline Vinblastines
Purine analogs
18 (94.7) 9 (47.4) 7 (36.8) 12 (63.2)
14 (100) 13 (92.9) 10 (71.4) 4 (28.6)
10 (100) 10 (100) 5 (50.0) 2 (20.0)
63 (98.4) 62 (96.9) 39 (60.9) 15 (23.4)
105 (98.1) 94 (87.9) 61 (57.0) 33 (30.8)
Rituximab-based therapy, N (%) Anti-CD20 antibody
12 (63.2)
9 (64.3)
9 (90.0)
57 (89.1)
87 (81.3)
BCR inhibitors, N (%)
8 (42.1)
3 (21.4)
3 (30.0)
5 (7.8)
19 (17.8)
Immunomodulators, N (%) BTK inhibitor
Pi3K inhibitors
BCL-2 inhibitor
5 (26.3) 8 (42.1) 0
2 (10.5)
1 (7.1) 3 (21.4)
0
0
2 (20.0) 1 (10.0) 0
12 (18.8) 4 (6.3) 3 (4.7) 0
18 (16.8) 17 (15.9) 4 (3.7) 2 (1.9)
Prior ASCT, N (%)
0
1 (7.1)
0
0
1 (0.9)
ASCT: autologous stem cell therapy; BCL-2: B-lymphocytoma-2; BCR: B-cell receptor; BTK: Bruton tyrosine kinase; CLL: chronic lymphocytic leukemia; DLBCL: diffuse large B-cell lymphoma; ECOG: Eastern Cooperative Oncology Group; IPI: International Prognostic Index; MCL: man- tle cell lymphoma; Pi3K: phosphatidylinositol 3-kinase; SLL: small lymphocytic lymphoma.
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