Trial Outcomes & Findings for A Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML) (NCT NCT03730012)

Last Updated: 2024-11-29

Results Overview

DLTs were defined as: * Confirmed Hy's Law case * Any Grade ≥ 3 non-hematologic or extramedullary toxicity with the following exceptions: * Anorexia or fatigue * Grade 3 nausea and/or vomiting if participant did not require tube feeding or total parenteral nutrition, or diarrhea if the events did not require or prolong hospitalization that could be managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset. * Grade 3 mucositis that resolved to Grade ≤ 2 within 7 days of onset * Grade 3 fever with neutropenia, with or without infection * Grade 3 infection * Grade 3 infusion-related toxicity, if successfully managed and resolved within 72 hours.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Day 1 up to 28 days

Results posted on

2024-11-29

Participant Flow

Study was planned for two phases, dose-escalation (phase 1) and dose expansion (phase 2). Sponsor decided not to open the phase 2 extension part of the study after completion of phase 1 dose escalation part.

Participants with relapsed or treatment refractory FMS-like tyrosine kinase 3 (FLT3) mutated acute myeloid leukemia (AML) were enrolled in this study.

Participant milestones

Participant milestones
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg Participants received 120 mg (milligrams) giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Overall Study STARTED	3	8
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	3	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg Participants received 120 mg (milligrams) giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Overall Study Adverse Event	0	1
Overall Study Lack of Efficacy	1	5
Overall Study Withdrawal by Subject	0	1
Overall Study Miscellaneous	2	1

Baseline Characteristics

A Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).	Total n=11 Participants Total of all reporting groups
Age, Continuous	78 years STANDARD_DEVIATION 8.7 • n=5 Participants	64.8 years STANDARD_DEVIATION 20.8 • n=7 Participants	68.4 years STANDARD_DEVIATION 18.9 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 up to 28 days

Population: Safety Population

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Number of Participants With Dose Limiting Toxicities (DLT)	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From the date of first dose up to end of treatment (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Population: The full analysis set (FAS) consisted of all participants who were enrolled in the study and took at least 1 dose of study drug (gilteritinib or atezolizumab).

CRc was defined as rate of all complete and incomplete remissions i.e. CR + CR with incomplete platelet recovery (CRp) + CR with incomplete hematological recover (CRi). Participants were classified as: CR if they achieved morphologic leukemia-free state \& their bone marrow was regenerating normal hematopoietic cells. If they had absolute neutrophil count (ANC) \> 1 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, normal marrow differential \< 5% blasts, \& were red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and platelet transfusion prior to disease assessment). There was also no evidence of extramedullary leukemia. CRp if they achieved CR with incomplete platelet recovery (\< 100 × 10\^9/L). CRi if they achieved CR with incomplete hematological recovery with residual neutropenia \< 1 × 10\^9/L, with or without complete platelet recovery. RBC and platelet transfusion independence was not required. Percentage of participants with CRc was reported.

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Composite Complete Remission (CRc) Rate	33.3 Percentage of participants Interval 0.8 to 90.6	12.5 Percentage of participants Interval 0.3 to 52.7

SECONDARY outcome

Timeframe: Pre-dose on C1D1, C1D8, C1D15, C2D1,C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C5D15, C6D1, C6D15

Population: The pharmacokinetic analysis set (PKAS) consisted of the administered population for which sufficient plasma concentration data was available to facilitate derivation of at least 1 PK parameter and for whom at least 1 plasma concentration datum was available and both the date and time of dosing on the day of PK sampling and the date and time of sampling were known. Participants with available data at specified time point were included.

Plasma Ctrough concentrations of gilteritinib was reported. One cycle = 28 days. C= cycle, D=day

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=7 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Plasma Ctrough Concentration of Gilteritinib Pre-dose C2D1	228 Nanogram per milliliter	422 Nanogram per milliliter Standard Deviation 328
Plasma Ctrough Concentration of Gilteritinib Pre-dose C1D1	NA Nanogram per milliliter Standard Deviation NA Concentrations below the limit of quantification (10 nanogram per milliliter)	NA Nanogram per milliliter Standard Deviation NA Concentrations below the limit of quantification (10 nanogram per milliliter)
Plasma Ctrough Concentration of Gilteritinib Pre-dose C1D8	355 Nanogram per milliliter Standard Deviation 240	302 Nanogram per milliliter Standard Deviation 155
Plasma Ctrough Concentration of Gilteritinib Pre-dose C1D15	483 Nanogram per milliliter Standard Deviation 272	553 Nanogram per milliliter Standard Deviation 436
Plasma Ctrough Concentration of Gilteritinib Pre-dose C2D15	—	83.3 Nanogram per milliliter
Plasma Ctrough Concentration of Gilteritinib Pre-dose C3D1	—	62.1 Nanogram per milliliter
Plasma Ctrough Concentration of Gilteritinib Pre-dose C3D15	—	75.2 Nanogram per milliliter

SECONDARY outcome

Timeframe: From the date of first dose up to end of treatment (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Population: FAS Population

Participants were classified as CR if they achieved a morphologic leukemia-free state and their bone marrow was regenerating normal hematopoietic cells. In addition, these participants had ANC \> 1 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, normal marrow differential with \< 5% blasts, and were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion prior to disease assessment). There was also no evidence of extramedullary leukemia. CR rate was defined as the number of participants with CR divided by the number of participants in the analysis population. Percentage of participants with CR was reported.

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Complete Remission (CR) Rate	33.3 Percentage of participants Interval 0.8 to 90.6	0 Percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From the date of first dose up to end of treatment (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Population: FAS Population

Participants were classified as CRh if they achieved CR with ANC level of \> 0.5 × 10\^9/L and platelet count of \> 50 × 10\^9/L. CRh rate was defined as the number of participants with CRh divided by the number of participants in the analysis population. Participants were classified as CR if they achieved a morphologic leukemia-free state and their bone marrow was regenerating normal hematopoietic cells. In addition, these participants had ANC \> 1 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, normal marrow differential with \< 5% blasts, and were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion prior to disease assessment). There was also no evidence of extramedullary leukemia. Percentage of participants with CRh was reported.

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Complete Remission With Partial Hematologic Recovery (CRh) Rate	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From the date of first dose up to end of treatment (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Population: FAS Population

Best response was defined as the best-measured response (CR, CRp, CRi or PR) post-treatment. Best response rate was defined as the number of participants with CR or CRp or CRi or PR divided by the number of participants in the analysis population (i.e., CR+ CRp + CRi + PR). Participants with unknown or missing response, or who provide no information on response at the end of study will be treated as non-responders and will be included in the denominator when calculating rates. CR, CRp and CRi were described in outcome measure 2#. Participants were classified as PR if their bone marrow was regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts and a decrease of at least 50% in the percentage of blasts in the bone marrow aspirate/biopsy, with the total marrow blasts between 5% and 25%. Percentage of participants with best response was reported.

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Best Response Rate	33.3 Percentage of participants Interval 0.8 to 90.6	25 Percentage of participants Interval 3.2 to 65.1

SECONDARY outcome

Timeframe: From date of first response until the date of documented relapse (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Population: FAS Population

DoR: duration of CRc, CR, CRi, CRp \& response (CRc + PR). Duration of CRc/CR/CRi/CRp: time from date of first CRc/CR/CRi/CRp until date of documented relapse for participants who achieved CRc/CR/CRi/CRp. Duration of response: time from date of either first CRc or PR until date of documented relapse of any type for participants who achieved CRc or PR. CRc, CR, CRi, CRp were described in outcome measure #2 \& PR was described in outcome measure #6. Relapse after CR, CRp or CRi: reappearance of leukemic blasts in peripheral blood or ≥ 5% blasts in bone marrow aspirate/biopsy not attributable to any other cause or reappearance or new appearance of extramedullary leukemia. Relapse after PR: reappearance of significant numbers of peripheral blasts \& an increase in the percentage of blasts in the bone marrow aspirate/biopsy to \> 25% not attributable to any other cause or reappearance or new appearance of extramedullary leukemia. Analysis was performed using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Duration of Remission (DoR)	NA Days Median, upper and lower limit of 95% CI were not estimable due to low number of events.	NA Days Interval 31.0 to Median and upper limit of 95% CI were not estimable due to low number of events.

SECONDARY outcome

Timeframe: From the date of first dose until the date of documented relapse from CR, CRp or CRi, treatment failure or death from any cause, whichever occurred first (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Population: FAS Population

EFS was defined as time from date of first dose until date of documented relapse from CR, CRp or CRi, treatment failure or death from any cause, whichever occurred first. CRc, CR, CRi, CRp were described in Outcome measure #2. For a participant with none of these events, EFS was censored at date of last disease assessment. Relapse after CR, CRp or CRi was defined as reappearance of leukemic blasts in peripheral blood or ≥ 5% blasts in bone marrow aspirate/biopsy not attributable to any other cause or reappearance or new appearance of extramedullary leukemia. Relapse after PR was defined with reappearance of significant numbers of peripheral blasts \& an increase in the percentage of blasts in the bone marrow aspirate/biopsy to \> 25% not attributable to any other cause or reappearance or new appearance of extramedullary leukemia. Treatment failure was defined as lack of CR, CRp or CRi, \& was determined at the end of treatment (EoT). Analysis was performed using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Event Free Survival (EFS)	175.00 Days Interval 71.0 to Upper limit of 95% CI was not estimable due to low number of events.	52.50 Days Interval 2.0 to 58.0

SECONDARY outcome

Timeframe: From the date of first dose until the date of death from any cause (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Population: FAS Population

OS was defined as the time from the date of first dose until the date of death from any cause. For a participant who was not known to have died by the end of study follow-up, overall survival was censored at the date of last contact. Analysis was performed using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Overall Survival (OS)	175.00 Days Interval 111.0 to Upper limit of 95% CI was not estimable due to low number of events.	NA Days Interval 51.0 to Median and upper limit of 95% CI was not estimable due to low number of events.

SECONDARY outcome

Timeframe: Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Population: Safety Population

An AE was any untoward medical occurrence in a participant administered study drug, \& which did not necessarily have to have a causal relationship with this treatment. Abnormalities was defined as AE only if met 1 of the criteria:Induced clinical signs/symptoms, required active intervention, required interruption or discontinuation of ST, abnormality or investigational value was clinically significant. Serious AE:resulted in death, was life threatening, persistent or significant disability/incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/birth defect, required hospitalization or prolongation of hospitalization, other medically important events. Any AE recorded on treatment including within 30 days from last study treatment was classified as treatment-emergent AE (TEAE). Grades(Gr) based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) (Gr 1=mild, Gr 2=moderate, Gr 3 =severe, Gr 4 =life threatening, Gr 5 =death).

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Number of Participants With Treatment-Emergent Adverse Events TEAE	3 Participants	8 Participants
Number of Participants With Treatment-Emergent Adverse Events Drug-Related Adverse Events	3 Participants	7 Participants
Number of Participants With Treatment-Emergent Adverse Events TEAE leading to Deaths	1 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events Drug-related TEAE Leading to Deaths	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events Serious Adverse Events	3 Participants	7 Participants
Number of Participants With Treatment-Emergent Adverse Events Drug-Related Serious Adverse Events	3 Participants	6 Participants
Number of Participants With Treatment-Emergent Adverse Events Adverse Events Leading to Withdrawal of Treatment	2 Participants	6 Participants
Number of Participants With Treatment-Emergent Adverse Events Drug-Related Adverse Events Leading to Withdrawal of Treatment	1 Participants	5 Participants
Number of Participants With Treatment-Emergent Adverse Events Grade 3 or Higher TEAE	3 Participants	8 Participants
Number of Participants With Treatment-Emergent Adverse Events Treatment Emergent Deaths	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and end of treatment (EoT) (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Population: Safety population with available data at specified timepoint

ECOG performance status was measured on an 6 point scale. 0-Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.

Outcome measures

Outcome measures
Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 Participants Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score Baseline: Grade 0	0 Participants	3 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score Baseline: Grade 1	3 Participants	4 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score Baseline: Grade 2	0 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score Baseline: Grade 3	0 Participants	0 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score Baseline: Grade 4	0 Participants	0 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score Baseline: Grade 5	0 Participants	0 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score EoT: Grade 0	0 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score EoT: Grade 1	1 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score EoT: Grade 2	0 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score EoT: Grade 3	1 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score EoT: Grade 4	0 Participants	0 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Score EoT: Grade 5	0 Participants	0 Participants

Adverse Events

Gilteritinib 120 mg + Atezolizumab 420 mg

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Gilteritinib 120 mg + Atezolizumab 840 mg

Serious events: 7 serious events

Other events: 8 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical trial Disclosure

Astellas Pharma Global Development, Inc

Phone: 800-888-7704

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Publication restrictions are in place

Restriction type: OTHER

Measure	Gilteritinib 120 mg + Atezolizumab 420 mg n=3 participants at risk Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).	Gilteritinib 120 mg + Atezolizumab 840 mg n=8 participants at risk Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 2 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Blood and lymphatic system disorders Febrile neutropenia	100.0% 3/3 • Number of events 6 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	62.5% 5/8 • Number of events 6 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Cardiac disorders Myocarditis	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Endocrine disorders Adrenal insufficiency	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
General disorders Fatigue	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
General disorders Pyrexia	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	37.5% 3/8 • Number of events 3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Hepatobiliary disorders Hepatitis	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Infections and infestations Bacteraemia	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Infections and infestations Enterocolitis infectious	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Infections and infestations Pneumonia	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	25.0% 2/8 • Number of events 3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Infections and infestations Sepsis	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Infections and infestations Urinary tract infection pseudomonal	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Injury, poisoning and procedural complications Fall	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Injury, poisoning and procedural complications Infusion related reaction	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Injury, poisoning and procedural complications Subdural haematoma	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Investigations Alanine aminotransferase increased	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Investigations Platelet count decreased	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Metabolism and nutrition disorders Adult failure to thrive	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Metabolism and nutrition disorders Hyperuricaemia	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	25.0% 2/8 • Number of events 2 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Nervous system disorders Cerebrovascular accident	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Nervous system disorders Encephalopathy	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Psychiatric disorders Delirium	66.7% 2/3 • Number of events 2 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	0.00% 0/8 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 2 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Respiratory, thoracic and mediastinal disorders Hypoxia	33.3% 1/3 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.00% 0/3 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)	12.5% 1/8 • Number of events 1 • Baseline to 30 days after last study treatment (Maximum treatment duration was 535 days for giltertinib and 112 days for atezolizumab)