Phase 2
Completed N=17
Phase I/II Trial of S64315 Plus Azacitidine in Acute Myeloid Leukaemia
Source: ClinicalTrials.gov NCT04629443 ↗Enrolled (actual)
17
Serious AEs
94.1%
Results posted
Jun 2024
Primary outcomePrimary: Dose Limiting Toxicity (DLT) (Phase I - Dose Escalation) — 0; 1; 1 Participants
Summary
The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S64315 with azacitidine in patients with acute myeloid leukaemia.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dose Limiting Toxicity (DLT) (Phase I - Dose Escalation) |
0; 1; 1 | — |
| PRIMARY Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation) |
72; 56; 41; 39; 22; 13 | — |
| PRIMARY Number of Serious Adverse Event (SAEs) and Fatal SAEs (Phase I - Dose Escalation) |
16; 14; 5; 2; 2; 0 | — |
| PRIMARY Number of Participants With Dose Interruptions (Phase I - Dose Escalation) |
3; 2; 1; 4; 4; 3 | — |
| PRIMARY Number of Participants With Dose Reductions (Phase I - Dose Escalation) |
1; 0; 0 | — |
| PRIMARY Dose Intensity for S64315 (Phase I - Dose Escalation) |
41.0; 60.3; 119.6 | — |
| PRIMARY Dose Intensity for Azacitidine (Phase I - Dose Escalation) |
23.5; 18.8; 22.9 | — |
| SECONDARY Assess Anti-leukemic Activity of S64315 in Combination With Azacitidine (Phase I - Dose Escalation) |
— | — |
| SECONDARY Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation) |
— | — |
| SECONDARY Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Area Under the Curve (AUC) (Phase I - Dose Escalation) |
1588; 1929; 7393; 2235; 8584 | — |
| SECONDARY Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Maximum Concentration (Cmax) (Phase I - Dose Escalation) |
923; 1021; 3646; 1850; 4520 | — |
Eligibility Criteria
Inclusion Criteria
- Patients aged ≥ 18 years
- Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization 2016 classification (Arber, 2016) excluding acute promyelocytic leukaemia (APL, French American-British M3 classification) with: relapsed or refractory disease and without established alternative therapy, or secondary to MyeloDysplastic Syndrome and without established alternative therapy or, newly diagnosed AML, not previously treated for AML and who are not candidate for intensive chemotherapy due to age or comorbidities.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Adequate haematological, renal and hepatic functions based on the last assessment performed within 7 days prior to the first Investigational Medicinal Product administration.
Exclusion Criteria
- Previous myeloproliferative syndrome (MPS).
- Patients previously treated with any Mcl-1 inhibitor.
- Patients who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 2 toxicity (except alopecia of any grade) according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) version 5.0, prior to the first IMP administration.
- Severe or uncontrolled active acute or chronic infection.
- Uncontrolled hepatitis B or C infection.
- Known carriers of HIV antibodies, history of significant liver disease, active acute or chronic pancreatitis, active central nervous system disease.
- Troponin > ULN (Upper Limit of reference range) or Troponin T > ULN if Troponin I cannot be assessed.
- Clinically significant cardiac dysfunction (including New York Heart Association class ≥II heart failure, Left Ventricular Ejection Fraction (LVEF) 450 ms for males and > 470 ms for females, obtained from triplicate 12-lead ECG.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.
- Uncontrolled arterial hypertension (systolic blood pressure (SBP) > 150 mmHg or diastolic blood pressure (DBP) > 95 mmHg).
Data sourced from ClinicalTrials.gov (NCT04629443). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.