TABLE 3.
Summary of TEAEs Reported by >10% of All Treated Subjects and Grade 3/4 Treatment-Emergent Laboratory Abnormalities Reported by >5% of All Treated Subjects
| Adverse Event Category and Term | Unesbulin 200 mg + DTIC 1,000 mg/m2 (n = 4), No. (%) | Unesbulin 300 mg + DTIC 1,000 mg/m2 (n = 33), No. (%) | Unesbulin 400 mg + DTIC 1,000 mg/m2 (n = 4), No. (%) | All Treated Subjects (N = 41), No. (%) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Grade 3 | Grade 4 | All | Grade 3 | Grade 4 | All | Grade 3 | Grade 4 | All | Grade 3 | Grade 4 | All | |
| Subjects with any TEAE | 2 (50.0) | 1 (25.0) | 4 (100) | 18 (54.5) | 10 (30.3) | 33 (100) | 0 | 4 (100) | 4 (100) | 20 (48.8) | 15 (36.6) | 41 (100) |
| Blood and lymphatic system disorders | ||||||||||||
| Anemia | 1 (25.0) | 0 | 1 (25.0) | 7 (21.2) | 0 | 16 (48.5) | 2 (50.0) | 0 | 2 (50.0) | 10 (24.4) | 0 | 19 (46.3) |
| GI | ||||||||||||
| Diarrhea | 0 | 0 | 1 (25.0) | 2 (6.1) | 0 | 19 (57.6) | 0 | 0 | 2 (50.0) | 2 (4.9) | 0 | 22 (53.7) |
| Nausea | 0 | 0 | 1 (25.0) | 1 (3.0) | 0 | 18 (54.5) | 0 | 0 | 1 (25.0) | 1 (2.4) | 0 | 20 (48.8) |
| Vomiting | 0 | 0 | 0 | 1 (3.0) | 0 | 9 (27.3) | 0 | 0 | 0 | 1 (2.4) | 0 | 9 (22.0) |
| Constipation | 0 | 0 | 0 | 0 | 0 | 6 (18.2) | 0 | 0 | 1 (25.0) | 0 | 0 | 7 (17.1) |
| Abdominal distension | 0 | 0 | 1 (25.0) | 0 | 0 | 4 (12.1) | 0 | 0 | 1 (25.0) | 0 | 0 | 6 (14.6) |
| Abdominal pain | 0 | 0 | 0 | 0 | 0 | 4 (12.1) | 0 | 0 | 2 (50.0) | 0 | 0 | 6 (14.6) |
| General disorders and administration site conditions | ||||||||||||
| Fatigue | 0 | 0 | 1 (25.0) | 4 (12.1) | 0 | 20 (60.6) | 0 | 0 | 3 (75.0) | 4 (9.8) | 0 | 24 (58.5) |
| Investigations | ||||||||||||
| Platelet count decreased | 1 (25.0) | 1 (25.0) | 3 (75.0) | 9 (27.3) | 5 (15.2) | 19 (57.6) | 0 | 3 (75.0) | 4 (100) | 10 (24.4) | 9 (22.0) | 26 (63.4) |
| Neutrophil count decreased | 1 (25.0) | 1 (25.0) | 2 (50.0) | 10 (30.3) | 6 (18.2) | 19 (57.6) | 0 | 3 (75.0) | 4 (100) | 11 (26.8) | 10 (24.4) | 25 (61.0) |
| Lymphocyte count decreased | 1 (25.0) | 0 | 2 (50.0) | 8 (24.2) | 0 | 16 (48.5) | 0 | 0 | 0 | 9 (22.0) | 0 | 18 (43.9) |
| WBC count decreased | 2 (50.0) | 0 | 2 (50.0) | 6 (18.2) | 1 (3.0) | 12 (36.4) | 4 (100) | 0 | 4 (100) | 12 (29.3) | 1 (2.4) | 18 (43.9) |
| Blood creatinine increased | 0 | 0 | 1 (25.0) | 0 | 0 | 5 (15.2) | 0 | 0 | 0 | 0 | 0 | 6 (14.6) |
| Cardiac disorders | ||||||||||||
| Sinus tachycardia | 0 | 0 | 0 | 0 | 0 | 4 (12.1) | 0 | 0 | 3 (75.0) | 0 | 0 | 7 (17.1) |
| Metabolism and nutrition disorders | ||||||||||||
| Decreased appetite | 0 | 0 | 1 (25.0) | 0 | 0 | 5 (15.2) | 0 | 0 | 1 (25.0) | 0 | 0 | 7 (17.1) |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Bone pain | 0 | 0 | 0 | 0 | 0 | 6 (18.2) | 0 | 0 | 1 (25.0) | 0 | 0 | 7 (17.1) |
| Myalgia | 0 | 0 | 0 | 0 | 0 | 2 (6.1) | 0 | 0 | 3 (75.0) | 0 | 0 | 5 (12.2) |
| Pain in extremity | 0 | 0 | 0 | 1 (3.0) | 0 | 4 (12.1) | 0 | 0 | 1 (25.0) | 1 (2.4) | 0 | 5 (12.2) |
| Nervous system disorders | ||||||||||||
| Headache | 0 | 0 | 0 | 0 | 0 | 5 (15.2) | 0 | 0 | 1 (25.0) | 0 | 0 | 6 (14.6) |
| Respiratory, thoracic, and mediastinal disorders | ||||||||||||
| Dyspnea | 0 | 0 | 0 | 0 | 0 | 5 (15.2) | 0 | 0 | 0 | 0 | 0 | 5 (12.2) |
| Vascular disorders | ||||||||||||
| Hypertension | 0 | 0 | 0 | 0 | 0 | 3 (9.1) | 0 | 0 | 2 (50.0) | 0 | 0 | 5 (12.2) |
NOTE. The number of subjects for each column, and the denominator for all percentages, is the number of subjects in the safety population by group. TEAE is defined as an AE with an onset date or worsening date on or after the date on which unesbulin or DTIC was first administered and within 30 days after the last dose. If a subject experienced multiple AEs under the same SOC, the subject was counted only once for the SOC with the greatest severity. Similarly, if a subject experienced multiple AEs under the same PT and SOC, the subject was counted only once for the PT with the greatest severity. The AE toxicity was graded on the basis of NCI CTCAE version 5.0. If a subject experienced the same AE multiple times, the maximum grade that the subject experienced the event was summarized. A DLT was defined as one of the AEs (listed in the protocol) assessed as being possible or probably related to study treatment administration that was not because of the underlying malignancy and had no clear evidence of an alternative etiology in the opinion of the investigator.
Abbreviations: AE, adverse event; DLT, dose-limiting toxicity; DTIC, dacarbazine; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; PT, preferred term; SOC, System Organ Class; TEAE, treatment-emergent adverse event.