Trial Outcomes & Findings for Assessing An Oral Janus Kinase Inhibitor, AZD4205 as Monotherapy in Patients Who Have PTCL (JACKPOT8) (NCT NCT04105010)

Last Updated: 2025-04-04

Results Overview

ORR is the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) based on CT scans evaluated by IRC per Lugano criteria.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

171 participants

Primary outcome timeframe

Up to approximately 3 years

Results posted on

2025-04-04

Participant Flow

DZ2019J0005 study includes 2 parts: Part A, the dose escalation and extension part (group A, B, C), and part B, dose expansion part (group D). 51 and 120 participants were recruited in Part A and Part B respectively, based on physician referral at 31 sites in the U.S., Australia, China and South Korea. The first participant was enrolled on 10-Sep-2019 and the last participant was enrolled on 23-Aug-2023.

171 enrolled participants met inclusion criteria and received study drug.

Participant milestones

Participant milestones
Measure	AZD4205 Group A Group A: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D Group D: Open label AZD4205 at the 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Overall Study STARTED	28	16	7	120
Overall Study COMPLETED	13	7	5	39
Overall Study NOT COMPLETED	15	9	2	81

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD4205 Group A Group A: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D Group D: Open label AZD4205 at the 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Overall Study Death	3	1	1	54
Overall Study Lost to Follow-up	0	0	0	4
Overall Study Withdrawal by Subject	8	1	1	4
Overall Study Other reason	4	7	0	19

Baseline Characteristics

Assessing An Oral Janus Kinase Inhibitor, AZD4205 as Monotherapy in Patients Who Have PTCL (JACKPOT8)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD4205 Group A n=28 Participants Group A: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=16 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=7 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=120 Participants Group D: Open label AZD4205 at the 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	Total n=171 Participants Total of all reporting groups
Age, Continuous	62.5 years n=5 Participants	61.5 years n=7 Participants	55.0 years n=5 Participants	58.0 years n=4 Participants	58.0 years n=21 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	44 Participants n=4 Participants	61 Participants n=21 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	13 Participants n=7 Participants	4 Participants n=5 Participants	76 Participants n=4 Participants	110 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	28 Participants n=5 Participants	16 Participants n=7 Participants	7 Participants n=5 Participants	100 Participants n=4 Participants	151 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	14 Participants n=4 Participants	14 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to approximately 3 years

Population: Evaluable for CT-based Response Set (all dosed and central pathology confirmed Peripheral T Cell Lymphoma (PTCL) patients with baseline measurable disease assessed by IRC using CT imaging)

ORR is the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) based on CT scans evaluated by IRC per Lugano criteria.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=102 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part B: CT-based Objective Response Rate (ORR) by Independent Review Committee (IRC)	43.1 percentage of participants Interval 33.4 to 53.3	—	—	—

SECONDARY outcome

Timeframe: The first dose until 28 days after last dose, up to approximately 3 years

To evaluate the safety and tolerability of AZD4205 in patients with PTCL in terms of adverse events (AEs), such as number of participants with AEs

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=28 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=16 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=7 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=120 Participants Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part A and Part B: Number of Participants With Adverse Events	26 Participants	16 Participants	6 Participants	115 Participants

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: Subset of CR or PR responders in Evaluable for CT-based Response Set

DoR is the time from the date of first documented response until the date of documented progression or death due to any cause. Documented response and progression are both identified based on CT scans evaluated by IRC per Lugano criteria.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=44 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part B: Duration of Response (DoR) Assessed by IRC	NA months Interval 16.6 to Not estimable due to insufficient number of participants with events	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: Evaluable for CT-based Response Set

CRR is the percentage of patients with at least one visit response of CR based on CT scans evaluated by IRC per Lugano criteria.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=102 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part B: Complete Response Rate (CRR) Assessed by IRC	21.6 percentage of participants Interval 14.0 to 30.8	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: Evaluable for Survival Set (all dosed and central pathology confirmed PTCL patients)

PFS is the time from the date of first dosing until the date of objective disease progression or death (by any cause) regardless of whether the participant discontinues the study treatments. Progression is identified based on CT scans evaluated by IRC per Lugano criteria.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=105 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part B: Progression Free Survival (PFS) Assessed by IRC	5.5 months Interval 3.0 to 18.7	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: Subset of CR or PR responders in Evaluable for CT-based Response Set

TTR is the time from the date of first dosing to the time of the initial response of PR or CR. Response is identified based on CT scans evaluated by IRC per Lugano criteria.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=44 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part B: Time to Response (TTR) Assessed by IRC	1.4 months Interval 1.4 to 1.5	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: Part A: Evaluable for Response Set (All dosed patients with baseline measurable disease) Part B: Evaluable for CT-based Response Set

ORR is the percentage of patients with at least one visit response of CR or PR based on CT and/or PET scans evaluated by investigator per Lugano criteria.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=28 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=16 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=7 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=102 Participants Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part A and Part B: ORR Assessed by Investigator	46.4 percentage of participants Interval 27.5 to 66.1	37.5 percentage of participants Interval 15.2 to 64.6	14.3 percentage of participants Interval 0.4 to 57.9	38.2 percentage of participants Interval 28.8 to 48.4

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: Part A: Subset of CR or PR responders in Evaluable for Response Set Part B: Subset of CR or PR responders in Evaluable for CT-based Response Set

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=13 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=6 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=1 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=39 Participants Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part A and Part B: DoR Assessed by Investigator	5.09 months Interval 2.04 to Not estimable due to insufficient number of participants with events	NA months Interval 2.07 to Not estimable due to insufficient number of participants with events	3.19 months Not estimable due to insufficient number of participants with events	NA months Interval 4.4 to Not estimable due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: Part A: Evaluable for Response Set Part B: Evaluable for CT-based Response Set

CRR is the percentage of patients with at least one visit response of CR based on CT and/or PET scans evaluated by investigator per Lugano criteria.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=28 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=16 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=7 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=102 Participants Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part A and Part B: CRR Assessed by Investigator	28.6 percentage of participants Interval 13.2 to 48.7	12.5 percentage of participants Interval 1.6 to 38.3	14.3 percentage of participants Interval 0.4 to 57.9	14.7 percentage of participants Interval 8.5 to 23.1

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: Part A: Safety Analysis Set Part B: Evaluable for Survival Set

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=28 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=16 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=7 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=105 Participants Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part A and Part B: PFS Assessed by Investigator	3.29 months Interval 1.31 to 3.58	2.50 months Interval 1.41 to Not estimable due to insufficient number of participants with events	3.32 months Interval 1.41 to 5.26	3.4 months Interval 1.7 to 5.6

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: Subset of CR or PR responders in Evaluable for CT-based Response Set

TTR is the time from the date of first dosing to the time of the initial response of PR or CR. Response is identified based on CT scans evaluated by investigator per Lugano criteria.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=39 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part B: TTR Assessed by Investigator	1.4 months Interval 1.4 to 1.5	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D).

Population: PK population (all dosed patients with at least one reportable AZD4205 plasma concentrations and no important AEs or protocol deviations that may impact PK) with Intensive PK sampling on Cycle 1, Day 1

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the single dose.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=27 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=16 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=7 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=38 Participants Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part A and Part B: Maximum Plasma Concentration (Cmax) of AZD4205	279.8 ng/mL Geometric Coefficient of Variation 29.2	512.0 ng/mL Geometric Coefficient of Variation 27.7	258.8 ng/mL Geometric Coefficient of Variation 36.9	229.2 ng/mL Geometric Coefficient of Variation 40.91

SECONDARY outcome

Timeframe: Cycle 1, Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D).

Population: PK population with Intensive PK sampling on Cycle 1, Day 1

Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear up/log down rule.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=27 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=16 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=7 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=38 Participants Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part A and Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of AZD4205	3592 h*ng/mL Geometric Coefficient of Variation 26.0	6755 h*ng/mL Geometric Coefficient of Variation 25.0	3276 h*ng/mL Geometric Coefficient of Variation 21.1	3271 h*ng/mL Geometric Coefficient of Variation 35.24

SECONDARY outcome

Timeframe: Cycle 2 Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D).

Population: PK population with Intensive PK sampling on Cycle 2, Day 1

Maximum observed plasma concentration (ng/mL) at steady state, obtained directly from the observed concentration versus time data. Calculated for the multiple doses.

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=20 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=7 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=6 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=23 Participants Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part A and Part B: Cmax,ss, at Steady State of AZD4205	673.5 ng/mL Geometric Coefficient of Variation 28.9	1152 ng/mL Geometric Coefficient of Variation 30.6	665.9 ng/mL Geometric Coefficient of Variation 27.4	539.0 ng/mL Geometric Coefficient of Variation 35.92

SECONDARY outcome

Population: PK population with Intensive PK sampling on Cycle 2, Day 1

Area under the plasma concentration-time curve from time zero to the last quantifiable time point at steady state, calculated by the linear up/log down rule

Outcome measures

Outcome measures
Measure	AZD4205 Group D n=20 Participants Group D: Open label AZD4205 at 150 mg (RP2D), once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group B n=7 Participants Group B: Open label AZD4205 at 250 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group C n=6 Participants Group C: Open label AZD4205 at 150 mg, once daily (Phase 1) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions	AZD4205 Group D n=23 Participants Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) AZD4205: AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions
Part A and Part B: AUCss, at Steady State of AZD4205	11978 h*ng/mL Geometric Coefficient of Variation 27.1	20991 h*ng/mL Geometric Coefficient of Variation 33.5	11822 h*ng/mL Geometric Coefficient of Variation 29.2	10000 h*ng/mL Geometric Coefficient of Variation 36.85

Adverse Events

AZD4205 Group A

Serious events: 12 serious events

Other events: 26 other events

Deaths: 3 deaths

AZD4205 Group B

Serious events: 9 serious events

Other events: 16 other events

Deaths: 2 deaths

AZD4205 Group C

Serious events: 1 serious events

Other events: 6 other events

Deaths: 1 deaths

AZD4205 Group D

Serious events: 44 serious events

Other events: 114 other events

Deaths: 54 deaths

Serious adverse events

Other adverse events

Additional Information

Rika Chen

Dizal Pharmaceuticals

Phone: 862161095875

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60