Phase 2
Completed N=19
A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)
Source: ClinicalTrials.gov NCT04079296 ↗Enrolled (actual)
19
Serious AEs
46.5%
Results posted
Jun 2024
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities (DLTs) — 0; 0; 0; 0 participants
Summary
The purpose of this study was to evaluate the safety and tolerability and to determine the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) of ASP7517.
This study also evaluated the clinical response of ASP7517 as well as other measures of anticancer activity of ASP7517.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0; 0; 0; 1 | — |
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAE) & Serious TEAE |
5; 5; 6; 12; 10; 1 | — |
| PRIMARY Phase 2: Composite Complete Remission (CRc) Rate for Participants With R/R AML |
0.0; 0.0; 14.3; 8.3 | — |
| PRIMARY Phase 2: Complete Remission + Bone Marrow Complete Remission + Partial Remission (CR + BM CR + PR) Rate for Participants With R/R Higher Risk MDS |
100.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at Cycle 1(C1) Day2(D2) |
1; 3; 3; 8; 6; 5 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C1D4 |
1; 3; 2; 5; 2; 5 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C1D8 |
1; 3; 2; 8; 4; 5 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C1D11 |
3; 2; 2; 5; 0; 1 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C1D15 |
2; 3; 3; 5; 5; 3 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C1D18 |
3; 3; 2; 3; 0; 1 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C1D22 |
2; 3; 3; 6; 3; 2 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C1D25 |
2; 3; 2; 3; 0; 1 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C2D1 |
1; 1; 2; 6; 4; 3 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C2D2 |
1; 1; 3; 5; 4; 3 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C2D4 |
1; 0; 3; 3; 2; 2 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C2D8 |
2; 0; 2; 6; 3; 2 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C2D15 |
2; 0; 2; 5; 3; 1 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C2D22 |
2; 0; 3; 3; 3; 1 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C3D1 |
2; 3; 0; 4; 1; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C3D15 |
1; 3; 2; 3; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C4D1 |
1; 2; 2; 3; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C4D15 |
1; 2; 1; 2; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C5D1 |
1; 2; 1; 3; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C5D15 |
1; 2; 0; 3; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C6D1 |
0; 0; 1; 3; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at C6D15 |
0; 1; 1; 1; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at End of Treatment (EOT) (Dose Escalation Phase) |
3; 1; 3; 2; 2; 3 | — |
| PRIMARY Number of Participants With ECOG Performance Status at EOT (Dose Expansion Phase) |
5; 2; 1; 6; 2; 1 | — |
| PRIMARY Number of Participants With ECOG Performance Status at Observation Period (OP) (Week 2) |
0; 0; 1; 2; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at OP (Week 4) |
1; 0; 0; 2; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at OP (Week 6) |
0; 2; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at OP (Week 8) |
1; 0; 0; 2; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at OP (Week 10) |
0; 2; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With ECOG Performance Status at OP (Week 12) |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Duration of Remission (DR) for Participants With R/R AML |
15.0; 55.0 | — |
| SECONDARY Duration of Remission (DR) for Participants With R/R Higher Risk MDS |
2.0 | — |
| SECONDARY Event Free Survival (EFS) |
44.0; 32.0; 58.0; 30.0; NA; 63.0 | — |
| SECONDARY Overall Survival (OS) |
159.0; 343.0; 162.0; 883.0; 88.5; 180.0 | — |
| SECONDARY CR for Participants With R/R AML |
0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Best Response (CRc + PR) Rates for Participants With R/R AML |
0.0; 0.0; 28.6; 25.0 | — |
| SECONDARY CRh for Participants With R/R AML |
0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY CR for Participants With R/R Higher Risk MDS |
0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Hematologic Improvement (HI) for Participants With R/R Higher Risk MDS |
0.0; 0.0; 0.0; 8.3; 0.0; 0.0 | — |
| SECONDARY Objective Response (OR) (CR + BM CR + PR + HI) Rates (ORR) for Participants With R/R Higher Risk MDS |
100.0; 0.0; 0.0; 8.3 | — |
Eligibility Criteria
Inclusion Criteria
- Subject diagnosed with R/R AML or R/R higher risk MDS is defined as:
- R/R AML: Morphologically documented primary or secondary AML by the WHO criteria (2016); and refractory to at least 2 cycles of induction chemotherapy/not a candidate for re-induction or relapsed after achieving remission with a prior therapy; and received all standard therapies including targeted therapies (unless the therapy is contraindicated or intolerable) which are known to provide clinical benefit in the opinion of the treating investigator; and received salvage therapy or is not a candidate for salvage therapy.
- R/R higher risk MDS: Has MDS by the WHO criteria (2016); and either relapsed after achieving remission or refractory to standard therapies, including ≥ 4 cycles of hypomethylating agents (unless the therapy is contraindicated or intolerable); and is classified as higher risk MDS with a score of > 3.5 by Revised International Prognostic Scoring System (IPSS-R) in MDS.
- Subject has an Eastern Cooperative Oncology Group performance status of ≤ 2.
- Subject must meet the following criteria as indicated on the clinical laboratory tests during screening period:
- Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × upper limit of normal (ULN).
- Serum total bilirubin ≤ 1.5 × ULN.
- Serum creatinine ≤ 1.5 × ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
- Platelets ≥ 50, 000/μL at cycle 1 day 1 (C1D1) in the dose escalation cohorts only.
- Subject has a life expectancy of ≥ 12 weeks at the time of screening.
- Subjects with AML must have peripheral blood absolute blast count of < 20,000/μL at C1D1. Note: Blast count can be controlled by hydroxyurea during screening period.
- Female subject is not pregnant and at least 1 of the following conditions apply:
- Not a woman of childbearing potential (WOCBP).
- WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 180 days after final study treatment administration.
- Female subject must agree not to breastfeed starting at screening and throughout the study period and for 180 days after the final study treatment administration.
- Female subject must not donate ova starting at first dose of investigational product (IP) and throughout the study period and for 180 days after final study treatment administration.
- Male subject with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 180 day after final study treatment administration.
- Male subject must not donate sperm during the treatment period and for 180 days after the final study treatment administration.
- Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 180 days after final study treatment administration.
- Subject agrees not to participate in another interventional study while receiving study treatment in the present study.
Exclusion Criteria
- Subject was diagnosed with acute promyelocytic leukemia.
- Subject has breakpoint cluster region-Abelson-positive leukemia (BCR-ABL).
- Subject has persistent non-hematological toxicities of ≥ grade 2 (National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI-CTCAE], version 5.0), with symptoms and objective findings from prior AML or MDS treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation or surgery).
- Subject has received any of the following therapies:
- Systemic immunomodulators or immunosuppressive drugs including steroids ≤ 28 days prior to C1D1 (steroids can be used if not intended for treatment of AML or MDS; steroids for AML/MDS related symptoms can be used at low doses [less than 10 mg/day dexamethasone]).
- Cytotoxic agents (except hydroxyurea given
Data sourced from ClinicalTrials.gov (NCT04079296). 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.