All Drugs and Chemicals

Terephthalic acid

Dose finding study. Number of arms dependant upon dose limiting toxicities.

Precomplexed powder in bottle formulation supplied as 135 mg in a 60 cc polyethylene terephthalate (PET) plastic bottle. Requires reconstitution by a pharmacist, must be stored securely, and protected from light.

Compound AC220

Guy Gammon, MB BS, MRCP

AC220 will be administered as a once daily oral solution given continuously as 28-day treatment cycles, without food and without any rest periods, as long as there is no evidence of disease progression or unacceptably severe adverse events (AEs) related to the study drug.

A phase 1 open-label, dose finding study of AC220 in patients with solid tumors.

Dose Finding, Safety and Tolerability Study for AC220 to Treat Advanced Solid Tumors

A Phase 1 Open-Label, Dose Finding, Safety and Tolerability Study of AC220 Administered Daily to Patients With Advanced Solid Tumors

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Daiichi Sankyo

Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Quizartinib

Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission \<12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.

Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-)

After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.

Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.

Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-)

After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.

Precomplexed powder in bottle formulation supplied as 200 mg in a 60 cc polyethylene terephthalate (PET) plastic bottle. Requires reconstitution by a pharmacist, must be stored securely, and protected from light.

Interim Chief Medical Officer

AC220 will be administered as a once daily oral solution given continuously as 28-day treatment cycles, without any rest periods, until disease progression, relapse, intolerance to the drug, or elective allogeneic hematopoietic stem cell transplantation (HSCT).

Efficacy Study for AC220 to Treat Acute Myeloid Leukemia (AML)

Phase 2 Open-Label, AC220 Monotherapy Efficacy (ACE) Study in Patients With Acute Myeloid Leukemia (AML) With and Without FLT3-ITD Activating Mutations

Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD\[+\] Participants)

Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission.

Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD\[-\] Participants)

Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission.

CRc is defined as composite complete remission (CR+CRp+CRi) - CR = complete remission; CRp = complete remission with incomplete platelet recovery; CRi = complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia = all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib = all criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion.

Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population).

The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of \>1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria.

Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population).

Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population).

Kaplan-Meier analysis of overall survival (Safety Population)

Early treatment-related deaths included all treatment-related deaths prior to the end of Cycle 3 with a 3-day window (Cycle 3 end date + 3 days), unless the death was following a CRc response assessed by the Investigator.

Of note, AML disease progression (which includes the verbatim terms of progressive disease, disease progression, and relapsed AML) is reported as an AE in the data output and in the in-text tables; however, it is not considered an AE because of the population under study and is not further discussed.

FLT3-ITD positive and negative populations will be divided into 2 cohorts as follows:

Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission \<12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.

Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-)

After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.

Cohort 1; ≥60 Years of Age

Cohort 2; ≥18 Years of Age

Total

Age, Continuous

Less than 60 years

At least 60 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

Netherlands

United States

Poland

Italy

United Kingdom

France

Germany

Spain

Region of Enrollment

Weight

Composite complete remission (CRc)

Complete remission (CR)

Complete remission with incomplete platelet (CRp)

Complete remission with incomplete hematologic CRi

Partial remission (PR)

No response (NR)

Unknown

Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission \<12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.

* Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0
* Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1
* Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1

After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.

Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.

* Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0
* Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0

Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0

After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.

Derived disease assessments were conducted in the Safety Population (FLT3-ITD \[+\] participants).

Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants)

Derived disease assessments were conducted in the Safety Population (FLT3-ITD \[-\] participants).

Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants)

FLT3-ITD(+)

FLT3-ITD(-)

Composite complete remission was assessed in the Safety Population.

Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status

Duration of composite complete remission was assessed in the Safety Population based on FLT3-ITD (+) participants available for this analysis (Cohort 1: n=63; Cohort 2: n=62).

Duration of Composite Complete Remission in FLT3-ITD (+) Participants Who Achieved CRc Based on All On-Treatment Data

Duration of composite complete remission was assessed in the Safety Population based on FLT3-ITD (-) participants available for this analysis (Cohort 1: n=16; Cohort 2: n=12).

Duration of Composite Complete Remission in FLT3-ITD (-) Participants Who Achieved CRc Based on All On-Treatment Data

Response (based on local morphology) was assessed in the Safety Population (FLT3-ITD \[+\] participants).

Duration of Any Response in FLT3-ITD (+) Participants

Response (based on local morphology) was assessed in the Safety Population (FLT3-ITD \[-\] participants).

Duration of Any Response in FLT3-ITD (-) Participants

Leukemia-free survival (based on local morphology) was assessed in the Safety Population (FLT3-ITD \[+\] participants).

Median Duration of Leukemia-free Survival in FLT3-ITD (+) Participants

Leukemia-free survival (based on local morphology) was assessed in the Safety Population (FLT3-ITD \[-\] participants).

Median Duration of Leukemia-free Survival in FLT3-ITD (-) Participants

Overall survival was assessed in the Safety Population (FLT3-ITD \[+\] participants).

Median Duration of Overall Survival in FLT3-ITD (+) Participants

Overall survival was assessed in the Safety Population (FLT3-ITD \[-\] participants).

Median Duration of Overall Survival in FLT3-ITD (-) Participants

Early treatment-related deaths were assessed in the Safety Population.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Dose Finding, Safety and Tolerability Study for AC220 to Treat Advanced Solid Tumors	NCT01049893	Solid Tumors	Compound AC220	18 Years -	Daiichi Sankyo
Efficacy Study for AC220 to Treat Acute Myeloid Leukemia (AML)	NCT00989261	Acute Myeloid L...	Compound AC220	18 Years - 85 Years	Daiichi Sankyo

Spots Global Cancer Trial Database for compound ac220