Trial Outcomes & Findings for A First-in-human Study to Evaluate the Safety and Tolerability of AZD8853 in Participants With Selected Advanced/Metastatic Solid Tumours (NCT NCT05397171)

Last Updated: 2024-10-01

Results Overview

The safety and tolerability of AZD8853 in participants with selected advanced/metastatic solid tumors was assessed. As per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, severity scale ranged from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. This outcome measure was assessed only for substudy 1 Part A.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

17 participants

Primary outcome timeframe

From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year)

Results posted on

2024-10-01

Participant Flow

This study was conducted from 07 Jun 2022 to 06 Jun 2023 at multiple centers in the United States of America and Canada.

Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment. Due to early termination of the study, only Part A was started, Parts B \& C were not started.

Participant milestones

Participant milestones
Measure	AZD8853 300 mg Participants with advanced/metastatic solid tumors received AZD8853 300 milligrams (mg) every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Overall Study STARTED	3	6	7
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	3	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD8853 300 mg Participants with advanced/metastatic solid tumors received AZD8853 300 milligrams (mg) every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Overall Study Death	2	3	3
Overall Study Study Terminated By Sponsor	1	2	3
Overall Study Withdrawal by Subject	0	1	1

Baseline Characteristics

A First-in-human Study to Evaluate the Safety and Tolerability of AZD8853 in Participants With Selected Advanced/Metastatic Solid Tumours

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	Total n=16 Participants Total of all reporting groups
Age, Continuous	62.0 Years STANDARD_DEVIATION 13.2 • n=5 Participants	62.8 Years STANDARD_DEVIATION 4.2 • n=7 Participants	65.1 Years STANDARD_DEVIATION 7.4 • n=5 Participants	63.7 Years STANDARD_DEVIATION 7.3 • n=4 Participants
Sex: Female, Male Female	NA Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	NA Participants n=4 Participants
Sex: Female, Male Male	NA Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	NA Participants n=4 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 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

PRIMARY outcome

Timeframe: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year)

Population: Safety set included all participants who received any amount of IP.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any AE	3 Participants	4 Participants	6 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any AE possibly related to treatment	1 Participants	0 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any serious adverse event (SAE)	1 Participants	3 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any SAE possibly related to treatment	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any AE leading to discontinuation of IP	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any AE leading to discontinuation of IP and possibly related to treatment	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any AE leading to interruption of IP	0 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any SAE leading to discontinuation of IP	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any SAE leading to discontinuation of IP and possibly related to treatment (IP)	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any AE of greater than or equal to (>=) CTCAE Grade 3	1 Participants	3 Participants	4 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any AE of >= CTCAE Grade 3 possibly related to treatment	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any SAE of >= CTCAE Grade 3 possibly related to treatment	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any SAE with outcome death	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any SAE with outcome death and possibly related to treatment	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any SAE of >= CTCAE Grade 3	1 Participants	3 Participants	2 Participants

PRIMARY outcome

Timeframe: From Cycle 1 Day 1 to end of Cycle 1 (21 days)

Population: DLT evaluable set included enrolled participants who completed the DLT evaluation period (defined as 21 days after receiving the first infusion of IP) with at least 75% dosing and had completed safety evaluation requirements during the DLT evaluation period.

DLTs (in dose escalation Parts only) of AZD8853 in participants with selected advanced/metastatic solid tumors was assessed. The DLTs are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) as per NCI-CTCAE version 5.0 non-hematological toxicity or hematological toxicity. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Number of Participants With Dose Limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: First dose until progression of disease (PD) or last evaluable assessment in the absence of progression (1 Year)

Population: Response evaluable set included all dosed participants who had measurable disease at baseline. Here, "number of participants analyzed" specifies all participants who were evaluated for this outcome measure.

ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Objective Response Rate (ORR)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 15 weeks

Population: Response evaluable set included all dosed participants who had measurable disease at baseline.

Disease control was defined as a best overall response (BOR) of confirmed CR or PR or having stable disease (SD) (without subsequent cancer therapy) maintained for greater than or equal to (\>=) 14 weeks (study week 15) from first IP. Disease control rate at study week 15 weeks (DCR-15) was defined as the percentage of participants who had disease control at study week 15 weeks. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Disease Control Rate (DCR) at 15 Weeks	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: First documented response until date of first documented disease progression or study end (1 Year)

Population: Response evaluable set included all dosed participants who had measurable disease at baseline. Only participants in the response evaluable set who had a response were planned to include. However, data was not evaluated for this outcome measure as there were no objective responses available for any participant at any dose level.

The DOR was defined as the time from the date of first documented response (which was subsequently confirmed) until the date of documented progression or death in the absence of disease progression. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: First dose until documented disease progression or study end (1 Year)

Population: Safety set included all participants who received any amount of IP.

The PFS was defined as the time from the start of study intervention until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from study intervention or received another anti-cancer therapy prior to progression. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Progression Free Survival (PFS)	1.31 Months Interval 1.18 to 3.38	1.23 Months Interval 1.15 to 3.15	1.25 Months Interval 0.95 to 3.29

SECONDARY outcome

Timeframe: Baseline (pre-treatment) up to Week 6 and Week 15

Population: Response evaluable set included all dosed participants who had measurable disease at baseline. Here, "n" (number analyzed in each raw) signifies the participants with available data that were analyzed for each timepoint for this outcome measure.

Tumor size was the sum of the longest diameters (or short axis measurements for lymph nodes) of the target lesions (TLs). Percentage change in tumor size was determined for participants with measurable disease at baseline. Baseline for Response evaluation criteria in solid tumors (RECIST) version 1.1 was defined as the last evaluable assessment prior to first IP dose. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Percentage Change From Baseline in Tumor Size Week 6	10.1 Percentage change in tumor size Interval -0.9 to 16.7	10.9 Percentage change in tumor size Interval -0.9 to 41.4	14.9 Percentage change in tumor size Interval 1.5 to 37.4
Percentage Change From Baseline in Tumor Size Week 15	46.5 Percentage change in tumor size Interval 46.5 to 46.5	5.7 Percentage change in tumor size Interval 5.7 to 5.7	70.0 Percentage change in tumor size Interval 13.2 to 126.7

SECONDARY outcome

Timeframe: First dose until study end (1 Year)

Population: Safety set included all participants who received any amount of IP.

Overall survival was defined as the time from the start of treatment until death due to any cause. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Overall Survival (OS)	4.47 Months Interval 2.92 to The median and 90% CI were calculated with the Kaplan Meier process (a process in medical research to measure the proportion of participants surviving for a certain time after receiving treatment) and were non estimable at the time of analysis as there was insufficient number of participants with the event of interest (less than 50% for the median estimate) occurred in the study.	5.45 Months Interval 2.3 to The median and 90% CI were calculated with the Kaplan Meier process (a process in medical research to measure the proportion of participants surviving for a certain time after receiving treatment) and were non estimable at the time of analysis as there was insufficient number of participants with the event of interest (less than 50% for the median estimate) occurred in the study.	NA Months Interval 0.95 to The median and 90% CI were calculated with the Kaplan Meier process (a process in medical research to measure the proportion of participants surviving for a certain time after receiving treatment) and were non estimable at the time of analysis as there was insufficient number of participants with the event of interest (less than 50% for the median estimate) occurred in the study.

SECONDARY outcome

Timeframe: Baseline (pre-treatment), Day 8 of Cycle 1, Days 1 and 8 of Cycle 2, Day 1 of Cycles 3, 4, 5, 7 (each cycle is equal to 21 days)

Population: Safety set included all participants who received any amount of IP. Here, "number of participants analyzed" specifies all participants who were evaluated for this outcome measure and "n" (number analyzed in each raw) signifies the participants with available data that were analyzed for each timepoint for this outcome measure.

Change in ctDNA is defined as the percentage change in ctDNA from baseline to each timepoint for the safety population. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline Cycle 1 Day 8	74.3700 Percentage change from baseline in ctDNA Standard Deviation 103.6200	30.2546 Percentage change from baseline in ctDNA Standard Deviation 98.8909	10.7795 Percentage change from baseline in ctDNA Standard Deviation 53.1457
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline Cycle 2 Day 1	92.1105 Percentage change from baseline in ctDNA Standard Deviation 83.4783	32.1430 Percentage change from baseline in ctDNA Standard Deviation 48.9060	20.7386 Percentage change from baseline in ctDNA Standard Deviation 78.4507
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline Cycle 2 Day 8	101.0003 Percentage change from baseline in ctDNA Standard Deviation 63.4941	84.2143 Percentage change from baseline in ctDNA Standard Deviation 101.8080	116.3071 Percentage change from baseline in ctDNA Standard Deviation 192.7165
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline Cycle 4 Day 1	-8.3636 Percentage change from baseline in ctDNA Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.	50.2904 Percentage change from baseline in ctDNA Standard Deviation 54.8320	21.4744 Percentage change from baseline in ctDNA Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline Cycle 3 Day 1	64.9807 Percentage change from baseline in ctDNA Standard Deviation 22.7578	131.5277 Percentage change from baseline in ctDNA Standard Deviation 161.3495	26.9231 Percentage change from baseline in ctDNA Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline Cycle 5 Day 1	64 Percentage change from baseline in ctDNA Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.	50.4363 Percentage change from baseline in ctDNA Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.	—
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline Cycle 7 Day 1	67.8182 Percentage change from baseline in ctDNA Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.	—	—

SECONDARY outcome

Timeframe: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)

Population: PK analysis set included all participants who received at least one dose of IP with at least one reportable concentration.

The pharmacokinetic (PK) (Cmax) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Maximum Observed Concentration (Cmax) of AZD8853	76.70 Micrograms per milliliter (ug/mL) Standard Deviation 3.439	339.5 Micrograms per milliliter (ug/mL) Standard Deviation 96.74	1121 Micrograms per milliliter (ug/mL) Standard Deviation 225.9

SECONDARY outcome

Timeframe: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)

Population: PK analysis set included all participants who received at least one dose of IP with at least one reportable concentration.

The PK (AUClast) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853	10080 Hoursmicrogram per milliliter (hug/mL) Standard Deviation 1789	49210 Hoursmicrogram per milliliter (hug/mL) Standard Deviation 12130	161100 Hoursmicrogram per milliliter (hug/mL) Standard Deviation 43070

SECONDARY outcome

Timeframe: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)

Population: PK analysis set included all participants who received at least one dose of IP with at least one reportable concentration.

The PK (AUC\[t1-t2\]) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Partial Area Under the Plasma Concentration-time Curve From Time 0 to 504 Hours Post Dose (AUC[0-504 Hours]) of AZD8853	11870 h*ug/mL Standard Deviation 2385	57230 h*ug/mL Standard Deviation 14760	189400 h*ug/mL Standard Deviation 56040

SECONDARY outcome

Timeframe: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)

Population: PK analysis set included all participants who received at least one dose of IP with at least one reportable concentration.

The PK (AUCinf) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD8853	14580 h*ug/mL Standard Deviation 4136	67480 h*ug/mL Standard Deviation 18490	223700 h*ug/mL Standard Deviation 79270

SECONDARY outcome

Timeframe: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 year)

Population: Immunogenicity analysis set included all participants who received at least one dose of IP who have a non-missing baseline ADA result and at least 1 non-missing post-baseline ADA result.

The immunogenicity of AZD8853 in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Number of Participants With Positive Anti-drug Antibody (ADA) of AZD8853	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 0 hours post EOI of Cycle 1 Day 1, Day 1 (Pre-dose) of Cycles 2 and 3 (each cycle equals to 21 days) and 90-days post EOT of 90 days follow-up

Population: PD analysis set included all participants who received at least one dose of IP with at least one reportable concentration. Here, "number of participants analyzed" specifies all participants who were evaluated for this outcome measure and "n" (number analyzed in each raw) signifies the participants with available data that were analyzed for each timepoint for this outcome measure.

The pharmacodynamics (PD) activity of AZD8853 by assessment of candidate biomarkers in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy1 Part A. End of infusion= EOI; End of treatment= EOT

Outcome measures

Outcome measures
Measure	AZD8853 300 mg n=3 Participants Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=6 Participants Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Percentage Change From Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels Cycle 1 Day 1: 0 hours post EOI	-97.7850 Percentage change from baseline in GDF15 Standard Deviation 0.1917	-99.2637 Percentage change from baseline in GDF15 Standard Deviation 0.1161	-99.7472 Percentage change from baseline in GDF15 Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.
Percentage Change From Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels 90 Days Follow-Up: 90 days post EOT	2164.2547 Percentage change from baseline in GDF15 Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.	1311.2845 Percentage change from baseline in GDF15 Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.	2513.913 Percentage change from baseline in GDF15 Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.
Percentage Change From Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels Cycle 2 Day 1 (Pre-dose)	324.2284 Percentage change from baseline in GDF15 Standard Deviation 103.7778	411.2175 Percentage change from baseline in GDF15 Standard Deviation 345.6173	165.9668 Percentage change from baseline in GDF15 Standard Deviation 82.9703
Percentage Change From Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels Cycle 3 Day 1 (Pre-dose)	636.8307 Percentage change from baseline in GDF15 Standard Deviation NA Here, 'NA' indicates that standard deviation was not calculated due to the presence of only one participant at this specific time point.	770.4598 Percentage change from baseline in GDF15 Standard Deviation 520.3336	212.5270 Percentage change from baseline in GDF15 Standard Deviation 111.5861

Adverse Events

AZD8853 300 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

AZD8853 1000 mg

Serious events: 3 serious events

Other events: 4 other events

Deaths: 3 deaths

AZD8853 3000 mg

Serious events: 2 serious events

Other events: 6 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	AZD8853 300 mg n=3 participants at risk Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 1000 mg n=6 participants at risk Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.	AZD8853 3000 mg n=7 participants at risk Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
Vascular disorders Syncope	33.3% 1/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Infections and infestations COVID-19	33.3% 1/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Infections and infestations Clostridium difficile infection	33.3% 1/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Gastrointestinal disorders Anal fistula	33.3% 1/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Infections and infestations Sepsis	33.3% 1/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Investigations Blood bilirubin increased	0.00% 0/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	16.7% 1/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Vascular disorders Embolism	0.00% 0/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	16.7% 1/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Cardiac disorders Cardiac arrest	0.00% 0/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	16.7% 1/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	16.7% 1/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	14.3% 1/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/3 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	0.00% 0/6 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.	14.3% 1/7 • From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year). Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.

Other adverse events

Additional Information

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