Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies

Figures & data

Table 1. Demographic and disease characteristics.

Characteristic	Overall N = 44
Sex, n (%)
Male	30 (68.2)
Female	14 (31.8)
Race, n (%)
White/Caucasian	36 (81.8)
Black/African American	5 (11.4)
Asian	1 (2.3)
Other	2 (4.5)
Age (years)
Mean (STD)	64.5 (15.1)
Median	67.0
Min, max	18, 82
Disease type, n (%)
AML	31 (70.5)
CMML	5 (11.4)
MDS	8 (18.2)
Time since initial diagnosis (months)
Median	10.4
Min, max	0.0, 156.6
Number of lines of prior systemic therapy for cancer
Median	3.0
Min, max	1, 11
1	11 (25)
2	8 (18.2)
3	6 (13.6)
≥4	16 (36.4)

AML: acute myeloid leukemia; CMML: chronic myelomonocytic leukemia; Max: maximum; MDS: myelodysplastic syndrome; Min: minimum; STD: standard deviation

Table 2. Summary of DLTs.

System Organ Class Preferred Term^c	24 mg^a N = 3 n (%)	48 mg^a N = 4 n (%)	120 mg^aN = 5 n (%)	170 mg^aN = 3 n (%)	230 mg^aN = 3 n (%)	300 mg^aN = 3 n (%)	400 mg^aN = 6 n (%)	225 mg^bN = 6 n (%)	275 mg^bN = 5 n (%)	Overall N = 38 n (%)
Patients with at least one DLT	0	0	0	0	0	0	1 (16.7)	2 (33.3)	4 (80.0)	7 (18.4)
Gastrointestinal disorders	0	0	0	0	0	0	0	1 (16.7)	4 (80.0)	5 (13.2)
Diarrhea	0	0	0	0	0	0	0	1 (16.7)	1 (20.0)	2 (5.3)
Nausea	0	0	0	0	0	0	0	0	2 (40.0)	2 (5.3)
Vomiting	0	0	0	0	0	0	0	0	2 (40.0)	2 (5.3)
General disorders and administration site conditions	0	0	0	0	0	0	1 (16.7)	1 (16.7)	0	2 (5.3)
Chills	0	0	0	0	0	0	0	1 (16.7)	0	1 (2.6)
Fatigue	0	0	0	0	0	0	1 (16.7)	0	0	1 (2.6)

AE: adverse event; DLT: dose-limiting toxicity; MedDRA: Medical Dictionary for Regulatory Activities; PT: preferred term; SOC: system organ class

Table is sorted in descending order of the frequencies of SOC, then PT in the overall column.

Only DLTs from cycle 1 are included in this table.

Table includes DLTs as assessed by the investigator.

^a Administered as capsules once daily.

^b Administered as tablets once daily.

^c AEs are coded into SOC and PT using MedDRA version 23.0. Patients are counted only once per SOC and per PT.

Figure 1. Mean pelabresib plasma profiles (semi-logarithmic scale). A) Mean pelabresib plasma profile over time at cycle 1 day 1. B) Mean pelabresib plasma profile over time at cycle 1 day 14.

Table 3. Treatment-emergent adverse events by relationship to study drug (incidence ≥10% of patients overall; safety population).

System Organ Class Preferred Term^c	24 mg^a N = 3 n (%)	48 mg^a N = 5 n (%)	120 mg^aN = 5 n (%)	170 mg^aN = 3 n (%)	230 mg^aN = 3 n (%)	300 mg^aN = 4 n (%)	400 mg^aN = 7 n (%)	225 mg^bN = 8 n (%)	275 mg^bN = 6 n (%)	Overall N = 44 n (%)
Patients with any drug-related TEAE^c	3 (100.0)	3 (60.0)	5 (100.0)	3 (100.0)	3 (100.0)	3 (75.0)	6 (85.7)	7 (87.5)	5 (83.3)	38 (86.4)
Gastrointestinal disorders	2 (66.7)	2 (40.0)	4 (80.0)	3 (100.0)	1 (33.3)	3 (75.0)	3 (42.9)	6 (75.0)	4 (66.7)	28 (63.6)
Nausea	2 (66.7)	2 (40.0)	2 (40.0)	3 (100.0)	0	1 (25.0)	1 (14.3)	4 (50.0)	3 (50.0)	18 (40.9)
Diarrhea	1 (33.3)	0	2 (40.0)	1 (33.3)	0	3 (75.0)	1 (14.3)	2 (25.0)	3 (50.0)	13 (29.5)
Vomiting	0	2 (40.0)	0	2 (66.7)	0	0	3 (42.9)	1 (12.5)	4 (66.7)	12 (27.3)
Metabolism and nutrition disorders	0	1 (20.0)	4 (80.0)	2 (66.7)	3 (100.0)	2 (50.0)	3 (42.9)	5 (62.5)	2 (33.3)	22 (50.0)
Decreased appetite	0	1 (20.0)	3 (60.0)	2 (66.7)	2 (66.7)	1 (25.0)	2 (28.6)	5 (62.5)	1 (16.7)	17 (38.6)
General disorders and administration site conditions	2 (66.7)	2 (40.0)	2 (40.0)	1 (33.3)	0	1 (25.0)	5 (71.4)	3 (37.5)	1 (16.7)	17 (38.6)
Fatigue	2 (66.7)	2 (40.0)	2 (40.0)	0	0	0	4 (57.1)	3 (37.5)	1 (16.7)	14 (31.8)
Investigations	2 (66.7)	1 (20.0)	0	1 (33.3)	0	1 (25.0)	2 (28.6)	4 (50.0)	2 (33.3)	13 (29.5)
Platelet count decreased	2 (66.7)	0	0	0	0	0	2 (28.6)	2 (25.0)	1 (16.7)	7 (15.9)
Nervous system disorders	0	1 (20.0)	2 (40.0)	1 (33.3)	0	1 (25.0)	2 (28.6)	3 (37.5)	0	10 (22.7)
Dysgeusia	0	1 (20.0)	1 (20.0)	1 (33.3)	0	1 (25.0)	1 (14.3)	3 (37.5)	0	8 (18.2)
Blood and lymphatic system disorders	1 (33.3)	0	0	0	1 (33.3)	0	3 (42.9)	1 (12.5)	1 (16.7)	7 (15.9)
Anemia	1 (33.3)	0	0	0	1 (33.3)	0	2 (28.6)	1 (12.5)	1 (16.7)	6 (13.6)

AE: adverse event; MedDRA: Medical Dictionary for Regulatory Activities; PT: preferred term; SOC: system organ class; TEAE: treatment-emergent AE

Table is sorted in descending order of the frequencies of SOC, then PT in the overall column.

^a Administered as capsules once daily.

^b Administered as tablets once daily.

^c AEs are coded into SOC and PT using MedDRA version 23.0. Patients are counted only once per SOC and per PT.

Data availability statement

Data sharing requests by qualified researchers pertaining to the MANIFEST phase 1 study will be considered only for noncommercial use on a case-by-case basis (to be approved by MorphoSys; [email protected]), starting 12 months from acceptance of the manuscript and until 36 months thereafter; approval may be subject to a data access agreement.