EHA Library - The official digital education library of European Hematology Association (EHA)

ALICE: AN AML STUDY WITH LSD1 INHIBITION IN COMBINATION WITH AZACITIDINE IN THE ELDERLY
Author(s): ,
Pau Montesinos
Affiliations:
Medical,Hospital Universitario La Fe,Valencia,Spain
,
Tim Somervaille
Affiliations:
Medical,University of Manchester,Manchester,United Kingdom
,
Olga Salamero
Affiliations:
Medical,Hospital Universitario Vall D'Hebron,Barcelona,Spain
,
Sonia Gutierrez
Affiliations:
Medical,Oryzon Genomics SA,Barcelona,Spain
,
Jordi Xaus
Affiliations:
Medical,Oryzon Genomics SA,Barcelona,Spain
,
Carlos Buesa
Affiliations:
Oryzon Genomics SA,Barcelona,Spain
,
Tamara Maes
Affiliations:
Oryzon Genomics SA,Barcelona,Spain
Roger Bullock
Affiliations:
Medical,Oryzon Genomics SA,Barcelona,Spain
EHA Library. Buesa C. 06/14/19; 266077; PF277
Carlos Buesa
Carlos Buesa
Contributions
Abstract

Abstract: PF277

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background

Acute Myeloid Leukaemia (AML) is primarily a disease of older people and its incidence is rising. Survival rates decrease with age as does the achievement of complete remission (CR) with current chemotherapy, for which there is no consensus for optimal re-therapy. Azacitidine is approved for AML with 20-30% blasts. Lysine-specific demethylase (LSD1) has been shown to be a partner in some gene transformations in AML and helps sustain the oncogenic process. Iadademstat (ORY-1001) is a highly potent and selective LSD1 inhibitor that has been shown to be effective in preclinical models (both alone or in combination with other compounds, including Azacitidine); and remarkably safe in a phase I study, where it also demonstrated preliminary anti-leukaemic activity as monotherapy.  Iadademstat in combination with azacitidine may thus offer a novel treatment option for a patient group with limited current options.

Aims

To assess safety, tolerability and dose finding of iadademstat in combination with azacitidine, and to measure the clinical activity such as time to response (TTR), duration of response (DOR) and objective response (OR) of this combination in older patients who are not eligible to be treated with intensive chemotherapy. Other assessments include haematological improvement and overall survival, along with PK/PD measures (including a set of 6 blood biomarkers).

Methods

This is a two-stage phase II multicentre open-label study of safety, tolerability, dose-finding and efficacy of iadademstat in combination with azacitidine in elderly patients. The dose finding stage will dose 12-18 patients with a starting dose of iadademstat of 90µg/m2/d. Depending on the DLTs observed, iadademstat may be escalated or de-escalated. Once the Recommended Phase II Dose (RP2D) is identified, an expansion cohort of 18 patients will be enrolled and treated with iadademstat combined with azacitidine. In all cases patients to be recruited correspond to subjects ≥ 60 years of age with AML according to World Health Organization (WHO) classification, who are considered by the investigator to be ineligible for intensive chemotherapy regimen at that time or have refused standard chemotherapy, and which may not have received prior treatment for AML other than Hydroxyurea.

Results

The patient assessments of all the enrolled study subjects will be presented as per May 2019 cut-off, with particular emphasis on available preliminary efficacy outcomes. Current recruitment rate suggests that the available data will include the safety data after the first-cycle of treatment of the first 8-10 participants.  Moreover, preliminary efficacy data of all subjects in any of the cycles will be also presented.

Conclusion

This first combination Phase IIa study with iadademstat aims to further extend the safety and efficacy of iadademstat in the oncology field; in this case, in older unfit leukemic patients as a first line treatment, providing initial support for the effect of its holistic unique MoA, which has been recently related to the potentiation of several other approaches, including immune-oncology therapies in solid tumors.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Clinical trial, Epigenetic, Therapy-related AML

Abstract: PF277

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background

Acute Myeloid Leukaemia (AML) is primarily a disease of older people and its incidence is rising. Survival rates decrease with age as does the achievement of complete remission (CR) with current chemotherapy, for which there is no consensus for optimal re-therapy. Azacitidine is approved for AML with 20-30% blasts. Lysine-specific demethylase (LSD1) has been shown to be a partner in some gene transformations in AML and helps sustain the oncogenic process. Iadademstat (ORY-1001) is a highly potent and selective LSD1 inhibitor that has been shown to be effective in preclinical models (both alone or in combination with other compounds, including Azacitidine); and remarkably safe in a phase I study, where it also demonstrated preliminary anti-leukaemic activity as monotherapy.  Iadademstat in combination with azacitidine may thus offer a novel treatment option for a patient group with limited current options.

Aims

To assess safety, tolerability and dose finding of iadademstat in combination with azacitidine, and to measure the clinical activity such as time to response (TTR), duration of response (DOR) and objective response (OR) of this combination in older patients who are not eligible to be treated with intensive chemotherapy. Other assessments include haematological improvement and overall survival, along with PK/PD measures (including a set of 6 blood biomarkers).

Methods

This is a two-stage phase II multicentre open-label study of safety, tolerability, dose-finding and efficacy of iadademstat in combination with azacitidine in elderly patients. The dose finding stage will dose 12-18 patients with a starting dose of iadademstat of 90µg/m2/d. Depending on the DLTs observed, iadademstat may be escalated or de-escalated. Once the Recommended Phase II Dose (RP2D) is identified, an expansion cohort of 18 patients will be enrolled and treated with iadademstat combined with azacitidine. In all cases patients to be recruited correspond to subjects ≥ 60 years of age with AML according to World Health Organization (WHO) classification, who are considered by the investigator to be ineligible for intensive chemotherapy regimen at that time or have refused standard chemotherapy, and which may not have received prior treatment for AML other than Hydroxyurea.

Results

The patient assessments of all the enrolled study subjects will be presented as per May 2019 cut-off, with particular emphasis on available preliminary efficacy outcomes. Current recruitment rate suggests that the available data will include the safety data after the first-cycle of treatment of the first 8-10 participants.  Moreover, preliminary efficacy data of all subjects in any of the cycles will be also presented.

Conclusion

This first combination Phase IIa study with iadademstat aims to further extend the safety and efficacy of iadademstat in the oncology field; in this case, in older unfit leukemic patients as a first line treatment, providing initial support for the effect of its holistic unique MoA, which has been recently related to the potentiation of several other approaches, including immune-oncology therapies in solid tumors.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Clinical trial, Epigenetic, Therapy-related AML

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