Page 157 - Haematologica Vol. 109 - July 2024

ARTICLE - Sovleplenib Syk inhibitor in R/R B-cell tumors
Y. Song et al.
1.9-not calculable [NC]) and median DOR (mDOR) was 11.0 months (95% CI: 4.7-NC). The median PFS (mPFS) was 8.3 months (95% CI: 1.8-16.5), and median TTP (mTTP) was 8.3 months (95% CI: 1.8-16.5).
Dose expansion
Cohort A: chronic lymphocytic leukemia/small lymphocytic lymphoma
Among CLL/SLL patients in the EEAS (N=16), ORR was 56.3% (95% CI: 29.9-80.2) per investigator assessments (Table 3; Online Supplementary Figure S1). The mean best percentage change in tumor burden from baseline in CLL/SLL patients was -66.58 (± 30.80%) (Online Supplementary Figure S1). mTTR was 1.9 months (95% CI: 1.8-1.9) and mDOR was 13.1 months (95% CI: 1.8-NC). In the SS (N=16), mPFS was 14.9 months (95% CI: 3.7-NC; Online Supplementary Figure S2).
Cohort B: aggressive B-cell lymphomas
Among aggressive B-cell lymphoma patients in the EEAS (N=9), ORR was 33.3% (95% CI: 7.5-70.1) per investigator assessments (Table 3; Online Supplementary Figure S1). The mean best percentage change in tumor burden from base- line in aggressive B-cell lymphoma patients was 21.90% (± 87.407%) (Online Supplementary Figure S1). In the SS (N=14), mTTP was 1.9 months (95% CI: 0.8-9.1) and mPFS was 1.9 months (95% CI: 0.8-9.1; Online Supplementary Figure S2).
Cohort C: mantle cell lymphoma
Among MCL patients in the EEAS (N=7), the ORR was 28.6% (95% CI: 3.7-71.0) per investigator assessments, and two
(28.6%) patients achieved PR (Table 3; Online Supplementary Figure S1). The mean best percentage change in tumor bur- den from baseline in MCL patients was -9.8% (± 28.265%) (Online Supplementary Figure S1). Kaplan-Meier plots of PFS are provided in Online Supplementary Figure S2.
Cohort D: indolent B-cell lymphoma
Per independent review committee assessments, eight (13.6%) patients in the EEAS for cohort D (N=59) achieved CR and 22 (37.3%) patients achieved PR; the overall ORR was 50.8% (95% CI: 37.5-64.1; Table 3; Figure 2). In addi- tion, 26 (44.1%) achieved SD. mTTR was 2.7 months (95% CI: 1.8-3.7), and mDOR was 15.7 months (95% CI: 7.4-NC). In the SS (N=64), mTTP was 12.0 months (95% CI: 8.2-NC), and mPFS was 12.0 months (95% CI: 6.3-NC). FL patients (grade 1, 2, 3a; EEAS, N=43) achieved an IRC-assessed ORR of 60.5% (95% CI: 44.4-75.0); with seven (16.3%) patients achieved CR and 19 (44.2%) patients achieved PR. The mDOR was not reached and 14 (32.6%) maintained SD. Among FL patients in the SS (N=47), mTTP was 12.0 months (95% CI: 8.2-NC) and mPFS was 11.0 months (95% CI: 6.3-NC). Among 14 MZL patients in the EEAS, the IRC-assessed ORR was 28.6% (95% CI: 8.4-58.1).
Tumor response per investigator assessments (Table 3; Online Supplementary Figures S1-3) was consistent with that per IRC assessments in cohort D.
The mean best percentage change in tumor burden from baseline based on investigator assessment was similar to that based on IRC assessment (Figure 2). Among 57 patients with change in tumor burden from baseline, the
Table 3. Anti-tumor activity of sovleplenib based on the efficacy evaluable analysis set in the dose-expansion phase.
Dose-expansion phase
CLL/SLL N=19
Aggressive B-cell lymphomas N=14
MCL N=10
Indolent B-cell lymphoma N=64
Total N=107
Efficacy evaluable (INV/IRCa), N
CR PR/PR-L SD
PD
16 1 4/4
61
91 2/0 15
70 2/0 41
59
INV 3, IRC 8 INV 25/0, IRC 22/0 INV 23b, IRC 26 INV 8, IRC 2
91 5 33/4 34b 15
Not evaluable, N
0
0
0
INV 0, IRC 1
0
ORR % (95% CI)
56.3 (29.9-80.2)
33.3 (7.5-70.1)
28.6 (3.7-71.0)
INV 47.5 (34.3-60.9) IRC 50.8 (37.5-64.1)
46.2 (35.6-56.9)
Median DOR in months (95% CI)
13.1 (1.8-NC)
5.3 (3.7-NC)
4.6 (1.9-NC)
INV 13.9 (6.4-NC) IRC 15.7 (7.4-NC)
13.1 (6.5-NC)
Median PFS in months (95% CI)c
14.9 (3.7-NC)
1.9 (0.8-9.1)
3.7 (0.9-NC)
INV 8.3 (5.5-16.6) IRC 12.0 (6.3-NC)
8.2 (5.5-12.0)
Median TTR in months (95% CI)
1.9 (1.8-1.9)
1.9 (1.8-NC)
1.9 (1.9-NC)
INV 2.0 (1.9-3.6) IRC 2.7 (1.8-3.7)
1.9 (1.9-2.0)
aIRC: tumor response in the indolent B-cell lymphoma cohort was assessed by the independent review committee (IRC) and investigators (INV), and in the other cohorts was assessed by the INV. bIncluding 1 patient with minor response. cMedian progression-free survival (PFS) was evaluated from the safety set. CI: confidence interval; CLL: chronic lymphocytic leukemia; CR: complete response; DOR: duration of response; MCL: mantle cell lymphoma; NC: not calculable; ORR: objective response rate; PD: progressive disease; PR: partial response; PR-L: partial response with increased lymphocyte count; SD: stable disease; SLL: small lymphocytic lymphoma; TTR: time to response.
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