Trial Outcomes & Findings for A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma (NCT NCT05205161)
NCT ID: NCT05205161
Last Updated: 2025-01-07
Results Overview
The safety and the tolerability of AZD0466 in patients with relapsed/ refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) was evaluated.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
7 participants
Primary outcome timeframe
Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
Results posted on
2025-01-07
Participant Flow
Participants were enrolled in the study from 05July 2022 (First subject in) to 17 August 2023 (Last subject last visit) at 24 sites in 8 countries.
Participants meeting the inclusion criteria were enrolled in the study. All the assessments were performed as per the schedule of the assessments.
Participant milestones
| Measure |
600 mg of AZD0466
Participants received 600mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
Participants received 2400mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
1
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
1
|
Reasons for withdrawal
| Measure |
600 mg of AZD0466
Participants received 600mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
Participants received 2400mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Overall Study
Study terminated by sponsor
|
3
|
3
|
1
|
Baseline Characteristics
A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma
Baseline characteristics by cohort
| Measure |
600 mg of AZD0466
n=3 Participants
Participants received 600mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400mg of AZD0466 in Part A of the treatment
|
Total
n=7 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
62.7 Years
STANDARD_DEVIATION 7.0 • n=5 Participants
|
44.0 Years
STANDARD_DEVIATION 16.1 • n=7 Participants
|
NA Years
STANDARD_DEVIATION NA • n=5 Participants
|
57.0 Years
STANDARD_DEVIATION 16.9 • n=4 Participants
|
|
Sex/Gender, Customized
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Sex/Gender, Customized
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Sex/Gender, Customized
Other
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 monthPopulation: The safety analysis included all participants who received at least one dose of AZD0466.
The safety and the tolerability of AZD0466 in patients with relapsed/ refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) was evaluated.
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AE)
Any AE
|
3 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AE)
Any possibly related AE
|
2 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AE)
Any AE of >= CTCAE grade 3
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AE)
Any Serious Adverse events (SAE)
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AE)
Any possibly related SAE
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AE)
Any SAE with outcome death
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AE)
Any SAE of >= CTCAE grade 3
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AE)
Any Adverse event of Special interest
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AE)
Any AE leading to discontinuation of AZD0466
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AE)
Any AE leading to AZD0466 drug interruption
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AE)
Any AE leading to AZD0466 dose reduction
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AE)
Any possibly related deaths
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 to end of Cycle 1 (28 days treatment cycle)Population: The safety analysis included all participants who received at least one dose of AZD0466.
The DLT of AZD0466 in participants with R/R B-NHL was evaluated.
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Number of Participants With Dose Limiting Toxicity (DLT)
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8, Cycle 2 Day 1Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The Cmax of AZD4320 was assessed to characterise the pharmacokinetic (PK) profile of AZD0466.
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320
Released AZD4320 (Cycle 2 Day 1)
|
585.9 nmol/L
Standard Deviation 345.7
|
1760 nmol/L
Standard Deviation 2174
|
—
|
|
Part A: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320
Total AZD4320 (Cycle 1 Day 8)
|
46860 nmol/L
Standard Deviation 11820
|
77090 nmol/L
Standard Deviation 28580
|
NA nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the Statistical Analysis Plan (SAP).
|
|
Part A: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320
Total AZD4320 (Cycle 2 Day 1)
|
47970 nmol/L
Standard Deviation 13460
|
72620 nmol/L
Standard Deviation 26820
|
—
|
|
Part A: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320
Released AZD4320 (Cycle 1 Day 8)
|
1035 nmol/L
Standard Deviation 619.4
|
3658 nmol/L
Standard Deviation 5033
|
NA nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8, Cycle 2 Day 1Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact PK.
The tmax of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) of AZD4320
Total AZD4320 (Cycle 1 Day 8)
|
1.133 hour
Interval 0.67 to 1.23
|
1.083 hour
Interval 1.0 to 1.52
|
NA hour
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) of AZD4320
Total AZD4320 (Cycle 2 Day 1)
|
1.917 hour
Interval 1.12 to 2.08
|
1.167 hour
Interval 1.0 to 2.03
|
—
|
|
Part A: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) of AZD4320
Released AZD4320 (Cycle 1 Day 8)
|
1.167 hour
Interval 1.13 to 1.23
|
2.017 hour
Interval 2.0 to 2.12
|
NA hour
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) of AZD4320
Released AZD4320 (Cycle 2 Day 1)
|
1.12 hour
Interval 1.12 to 1.17
|
2.033 hour
Interval 2.0 to 2.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8 (Study Day 8), Cycle 2 Day 1 (Study Day 22)Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The λz of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) of AZD4320
Released AZD4320 (Cycle 2 Day 1)
|
NA 1/hour
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
NA 1/hour
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
—
|
|
Part A: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) of AZD4320
Total AZD4320 (Cycle 1 Day 8)
|
0.05729 1/hour
Standard Deviation 0.003854
|
0.06054 1/hour
Standard Deviation 0.005678
|
NA 1/hour
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) of AZD4320
Total AZD4320 (Cycle 2 Day 1)
|
0.06238 1/hour
Standard Deviation 0.01430
|
0.06157 1/hour
Standard Deviation 0.008283
|
—
|
|
Part A: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) of AZD4320
Released AZD4320 (Cycle 1 Day 8)
|
0.02643 1/hour
Standard Deviation 0.006131
|
0.03251 1/hour
Standard Deviation 0.008458
|
NA 1/hour
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8, Cycle 2 Day 1Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The t1/2λz of AZD4320 was assessed to characterise Pk profile of AZD0466.
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) of AZD4320
Total AZD4320 (Cycle 1 Day 8)
|
12.14 hour
Standard Deviation 0.8454
|
11.52 hour
Standard Deviation 1.062
|
NA hour
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) of AZD4320
Total AZD4320 (Cycle 2 Day 1)
|
11.48 hour
Standard Deviation 2.389
|
11.39 hour
Standard Deviation 1.515
|
—
|
|
Part A: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) of AZD4320
Released AZD4320 (Cycle 1 Day 8)
|
27.35 hour
Standard Deviation 7.302
|
22.22 hour
Standard Deviation 5.234
|
NA hour
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) of AZD4320
Released AZD4320 (Cycle 2 Day 1)
|
NA hour
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
NA hour
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8, Cycle 2 Day 1Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The AUC0-24 of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After the Start of Infusion (AUC0-24) of AZD4320
Total AZD4320 (Cycle 1 Day 8)
|
429900 h*nmol/L
Standard Deviation 143900
|
736800 h*nmol/L
Standard Deviation 405900
|
NA h*nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After the Start of Infusion (AUC0-24) of AZD4320
Total AZD4320 (Cycle 2 Day 1)
|
479200 h*nmol/L
Standard Deviation 204200
|
660700 h*nmol/L
Standard Deviation 388900
|
—
|
|
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After the Start of Infusion (AUC0-24) of AZD4320
Released AZD4320 (Cycle 1 Day 8)
|
7112 h*nmol/L
Standard Deviation 4377
|
30340 h*nmol/L
Standard Deviation 40570
|
NA h*nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After the Start of Infusion (AUC0-24) of AZD4320
Released AZD4320 (Cycle 2 Day 1)
|
NA h*nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
NA h*nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The AUC0-72 of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (AUC0-72) of AZD4320
Released AZD4320 (Cycle 1 Day 8)
|
13320 h*nmol/L
Standard Deviation 8190
|
36710 h*nmol/L
Standard Deviation 42900
|
NA h*nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (AUC0-72) of AZD4320
Total AZD4320 (Cycle 1 Day 8)
|
565200 h*nmol/L
Standard Deviation 193800
|
930500 h*nmol/L
Standard Deviation 543900
|
NA h*nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8, Cycle 2 Day 1Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The AUClast of AZD4320 was assessed to characterise the Pk profile of AZD0466
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Area Under the Plasma Concentration-curve From Time 0 to the Last Quantifiable Concentration (AUClast) of AZD4320
Total AZD4320 (Cycle 1 Day 8)
|
566000 h*nmol/L
Standard Deviation 190300
|
930200 h*nmol/L
Standard Deviation 543800
|
NA h*nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Area Under the Plasma Concentration-curve From Time 0 to the Last Quantifiable Concentration (AUClast) of AZD4320
Total AZD4320 (Cycle 2 Day 1)
|
473600 h*nmol/L
Standard Deviation 204500
|
634800 h*nmol/L
Standard Deviation 360600
|
—
|
|
Part A: Area Under the Plasma Concentration-curve From Time 0 to the Last Quantifiable Concentration (AUClast) of AZD4320
Released AZD4320 (Cycle 2 Day 1)
|
6616 h*nmol/L
Standard Deviation 3688
|
18520 h*nmol/L
Standard Deviation 22660
|
—
|
|
Part A: Area Under the Plasma Concentration-curve From Time 0 to the Last Quantifiable Concentration (AUClast) of AZD4320
Released AZD4320 (Cycle 1 Day 8)
|
12800 h*nmol/L
Standard Deviation 8628
|
36690 h*nmol/L
Standard Deviation 42910
|
NA h*nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8, Cycle 2 Day 1Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The tlast of AZD4320 was assessed to characterise the Pk profile of AZD0466
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Time of Last Observed (Quantifiable) Concentration (Tlast) of AZD4320
Total AZD4320 (Cycle 1 Day 8)
|
72.117 hour
Interval 69.05 to 95.87
|
71.683 hour
Interval 70.93 to 71.75
|
NA hour
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Time of Last Observed (Quantifiable) Concentration (Tlast) of AZD4320
Total AZD430 (Cycle 2 Day 1)
|
23.233 hour
Interval 22.1 to 24.22
|
22.333 hour
Interval 22.0 to 23.5
|
—
|
|
Part A: Time of Last Observed (Quantifiable) Concentration (Tlast) of AZD4320
Released AZD4320 (Cycle 1 Day 8)
|
1.167 hour
Interval 1.13 to 1.23
|
2.017 hour
Interval 2.0 to 2.12
|
NA hour
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Time of Last Observed (Quantifiable) Concentration (Tlast) of AZD4320
Released AZD4320 (Cycle 2 Day 1)
|
23.233 hour
Interval 22.1 to 24.22
|
22.333 hour
Interval 22.0 to 23.5
|
—
|
SECONDARY outcome
Timeframe: Cycle 2 Day 1Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The Ctrough of AZD4320 was assessed to characterise the Pk profile of AZD0466
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Concentration Prior to Dosing (Ctrough) of AZD4320
Total AZD430 (Cycle 2 Day 1)
|
NA nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
48.80 nmol/L
Standard Deviation 43.96
|
—
|
|
Part A: Concentration Prior to Dosing (Ctrough) of AZD4320
Released AZD4320 (Cycle 2 Day 1)
|
NA nmol/L
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
2.277 nmol/L
Standard Deviation 2.145
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8, Cycle 2 Day 1Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The Dose normalised AUClast of total AZD4320 was assessed to characterise the Pk profile of AZD0466
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A:Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Analyte Concentration Divided by the Dose Administered (Dose Normalised AUClast) of AZD4320
Total AZD430 (Cycle 1 Day 8)
|
943.4 h*nmol/L/mg
Standard Deviation 317.2
|
775.1 h*nmol/L/mg
Standard Deviation 453.2
|
NA h*nmol/L/mg
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A:Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Analyte Concentration Divided by the Dose Administered (Dose Normalised AUClast) of AZD4320
Total AZD430 (Cycle 2 Day 1)
|
789.4 h*nmol/L/mg
Standard Deviation 340.8
|
529.0 h*nmol/L/mg
Standard Deviation 300.5
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The Dose normalised AUC0-72 of total AZD4320 was assessed to characterise the Pk profile of AZD0466
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (Dose Normalised AUC0-72) of AZD4320
|
942.0 h*nmol/L/mg
Standard Deviation 323.0
|
775.4 h*nmol/L/mg
Standard Deviation 453.3
|
NA h*nmol/L/mg
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8, Cycle 2 Day 1Population: The Pk analysis set included dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may impact Pk.
The Dose normalised Cmax of total AZD4320 was assessed to characterise the Pk profile of AZD0466
Outcome measures
| Measure |
600mg of AZD0466
n=3 Participants
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 Participants
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 Participants
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Part A: Maximum Observed Plasma (Peak) Drug Concentration Divided by the Dose Administered (Dose Normalised Cmax) of AZD4320
Total AZD4320 (Cycle 1 Day 8)
|
78.11 nmol/L/mg
Standard Deviation 19.70
|
64.24 nmol/L/mg
Standard Deviation 23.81
|
NA nmol/L/mg
Standard Deviation NA
Due to insufficient number of participants (less than 3), no summary statistics were presented as per methodology mentioned in the SAP.
|
|
Part A: Maximum Observed Plasma (Peak) Drug Concentration Divided by the Dose Administered (Dose Normalised Cmax) of AZD4320
Total AZD4320 (Cycle 2 Day 1)
|
79.95 nmol/L/mg
Standard Deviation 22.44
|
60.51 nmol/L/mg
Standard Deviation 22.35
|
—
|
Adverse Events
600mg of AZD0466
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
1200 mg of AZD0466
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
2400 mg of AZD0466
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
600mg of AZD0466
n=3 participants at risk
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 participants at risk
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 participants at risk
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Investigations
Troponin increased
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
100.0%
1/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
Other adverse events
| Measure |
600mg of AZD0466
n=3 participants at risk
Participants received 600 mg of AZ0466 in Part A of the treatment
|
1200 mg of AZD0466
n=3 participants at risk
Participants received 1200 mg of AZD0466 in Part A of the treatment
|
2400 mg of AZD0466
n=1 participants at risk
Participants received 2400 mg of AZD0466 in Part A of the treatment
|
|---|---|---|---|
|
Infections and infestations
COVID-19
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Infections and infestations
Cystitis
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Infections and infestations
Nasopharyngitis
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
100.0%
1/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Vascular disorders
Hypertension
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Vascular disorders
Phlebitis
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
General disorders
Discomfort
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
General disorders
Fatigue
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
General disorders
Pyrexia
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Investigations
Neutrophil count decreased
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
33.3%
1/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
|
Investigations
Platelet count decreased
|
66.7%
2/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
66.7%
2/3 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
0.00%
0/1 • Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
|
Additional Information
Global Clinical Lead
AstraZeneca Clinical Study Information Center
Phone: 1-877-240-9479
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.
- Publication restrictions are in place
Restriction type: OTHER