Last reviewed · How we verify

NCT05397171

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

Terminated Phase 1, PHASE2 Results posted Last updated 1 October 2024
What this trial tests

Phase 1, PHASE2 trial testing AZD8853 in Urinary Bladder Neoplasms in 17 participants. Terminated before completion.

Timeline
7 June 2022
Primary endpoint
6 June 2023
6 June 2023

Quick facts

Lead sponsorAstraZeneca
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment17
Start date7 June 2022
Primary completion6 June 2023
Estimated completion6 June 2023
Sites6 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with Urinary Bladder Neoplasms or Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Primary · From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year)

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.

Any AE
GroupValue95% CI
AZD8853 300 mg3
AZD8853 1000 mg4
AZD8853 3000 mg6
Any AE possibly related to treatment
GroupValue95% CI
AZD8853 300 mg1
AZD8853 1000 mg0
AZD8853 3000 mg2
Any serious adverse event (SAE)
GroupValue95% CI
AZD8853 300 mg1
AZD8853 1000 mg3
AZD8853 3000 mg2
Any SAE possibly related to treatment
GroupValue95% CI
AZD8853 300 mg0
AZD8853 1000 mg0
AZD8853 3000 mg0
Any SAE with outcome death
GroupValue95% CI
AZD8853 300 mg0
AZD8853 1000 mg1
AZD8853 3000 mg0
Any SAE with outcome death and possibly related to treatment
GroupValue95% CI
AZD8853 300 mg0
AZD8853 1000 mg0
AZD8853 3000 mg0
Any AE leading to discontinuation of IP
GroupValue95% CI
AZD8853 300 mg0
AZD8853 1000 mg1
AZD8853 3000 mg0
Any AE leading to discontinuation of IP and possibly related to treatment
GroupValue95% CI
AZD8853 300 mg0
AZD8853 1000 mg0
AZD8853 3000 mg0
Number of Participants With Dose Limiting Toxicity (DLT) Primary · From Cycle 1 Day 1 to end of Cycle 1 (21 days)

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.

GroupValue95% CI
AZD8853 300 mg0
AZD8853 1000 mg0
AZD8853 3000 mg0
Objective Response Rate (ORR) Secondary · First dose until progression of disease (PD) or last evaluable assessment in the absence of progression (1 Year)

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.

GroupValue95% CI
AZD8853 300 mg0
AZD8853 1000 mg0
AZD8853 3000 mg0
Disease Control Rate (DCR) at 15 Weeks Secondary · 15 weeks

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.

GroupValue95% CI
AZD8853 300 mg1
AZD8853 1000 mg0
AZD8853 3000 mg1
Progression Free Survival (PFS) Secondary · First dose until documented disease progression or study end (1 Year)

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.

GroupValue95% CI
AZD8853 300 mg1.311.18 – 3.38
AZD8853 1000 mg1.231.15 – 3.15
AZD8853 3000 mg1.250.95 – 3.29
Percentage Change From Baseline in Tumor Size Secondary · Baseline (pre-treatment) up to Week 6 and Week 15

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.

Week 6
GroupValue95% CI
AZD8853 300 mg10.1-0.9 – 16.7
AZD8853 1000 mg10.9-0.9 – 41.4
AZD8853 3000 mg14.91.5 – 37.4
Week 15
GroupValue95% CI
AZD8853 300 mg46.546.5 – 46.5
AZD8853 1000 mg5.75.7 – 5.7
AZD8853 3000 mg70.013.2 – 126.7
Overall Survival (OS) Secondary · First dose until study end (1 Year)

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.

GroupValue95% CI
AZD8853 300 mg4.472.92 – NA
AZD8853 1000 mg5.452.30 – NA
AZD8853 3000 mgNA0.95 – NA
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline Secondary · 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)

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.

Cycle 1 Day 8
GroupValue95% CI
AZD8853 300 mg74.3700± 103.6200
AZD8853 1000 mg30.2546± 98.8909
AZD8853 3000 mg10.7795± 53.1457
Cycle 2 Day 1
GroupValue95% CI
AZD8853 300 mg92.1105± 83.4783
AZD8853 1000 mg32.1430± 48.9060
AZD8853 3000 mg20.7386± 78.4507
Cycle 2 Day 8
GroupValue95% CI
AZD8853 300 mg101.0003± 63.4941
AZD8853 1000 mg84.2143± 101.8080
AZD8853 3000 mg116.3071± 192.7165
Cycle 3 Day 1
GroupValue95% CI
AZD8853 300 mg64.9807± 22.7578
AZD8853 1000 mg131.5277± 161.3495
AZD8853 3000 mg26.9231± NA
Cycle 4 Day 1
GroupValue95% CI
AZD8853 300 mg-8.3636± NA
AZD8853 1000 mg50.2904± 54.8320
AZD8853 3000 mg21.4744± NA
Cycle 5 Day 1
GroupValue95% CI
AZD8853 300 mg64± NA
AZD8853 1000 mg50.4363± NA
Cycle 7 Day 1
GroupValue95% CI
AZD8853 300 mg67.8182± NA
Maximum Observed Concentration (Cmax) of AZD8853 Secondary · 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)

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.

GroupValue95% CI
AZD8853 300 mg76.70± 3.439
AZD8853 1000 mg339.5± 96.74
AZD8853 3000 mg1121± 225.9
Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853 Secondary · 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)

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.

GroupValue95% CI
AZD8853 300 mg10080± 1789
AZD8853 1000 mg49210± 12130
AZD8853 3000 mg161100± 43070
Partial Area Under the Plasma Concentration-time Curve From Time 0 to 504 Hours Post Dose (AUC[0-504 Hours]) of AZD8853 Secondary · 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)

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.

GroupValue95% CI
AZD8853 300 mg11870± 2385
AZD8853 1000 mg57230± 14760
AZD8853 3000 mg189400± 56040
Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD8853 Secondary · 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)

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.

GroupValue95% CI
AZD8853 300 mg14580± 4136
AZD8853 1000 mg67480± 18490
AZD8853 3000 mg223700± 79270

Adverse events — posted to ClinicalTrials.gov

Time frame: From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AZD8853 300 mg
Serious: 2/3 (67%)
Deaths: 2/3
AZD8853 1000 mg
Serious: 3/6 (50%)
Deaths: 3/6
AZD8853 3000 mg
Serious: 2/7 (29%)
Deaths: 3/7

Serious adverse events (11 terms)

ReactionSystemAZD8853 300 mgAZD8853 1000 mgAZD8853 3000 mg
SyncopeVascular disorders
COVID-19Infections and infestations
Clostridium difficile infectionInfections and infestations
Anal fistulaGastrointestinal disorders
SepsisInfections and infestations
Blood bilirubin increasedInvestigations
EmbolismVascular disorders
Cardiac arrestCardiac disorders
Back painMusculoskeletal and connective tissue disorders
Small intestinal obstructionGastrointestinal disorders
Femoral neck fractureInjury, poisoning and procedural complications
Other adverse events (49 terms — click to expand)

ReactionSystemAZD8853 300 mgAZD8853 1000 mgAZD8853 3000 mg
DiarrhoeaGastrointestinal disorders
Abdominal painGastrointestinal disorders
PyrexiaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
FatigueGeneral disorders
Back painMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Blood alkaline phosphatase increasedInvestigations
AnaemiaBlood and lymphatic system disorders
DehydrationMetabolism and nutrition disorders
HypotensionVascular disorders
HyponatraemiaMetabolism and nutrition disorders
ChillsGeneral disorders
Sacral painMusculoskeletal and connective tissue disorders
Sinus tachycardiaCardiac disorders
ConstipationGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
HaematomaVascular disorders
MyalgiaMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Localised oedemaGeneral disorders
Supraventricular tachycardiaCardiac disorders
Abdominal pain lowerGastrointestinal disorders
VomitingGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Oral painGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
HypersensitivityImmune system disorders
COVID-19 pneumoniaInfections and infestations
Tooth infectionInfections and infestations
Vascular access complicationInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Weight decreasedInvestigations
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Blood creatine phosphokinase increasedInvestigations
Weight increasedInvestigations
HypophosphataemiaMetabolism and nutrition disorders

Most-reported serious reactions: Syncope, COVID-19, Clostridium difficile infection, Anal fistula, Sepsis, Blood bilirubin increased, Embolism, Cardiac arrest.

Data from ClinicalTrials.gov NCT05397171 adverse events section.

Sponsor's own description

A Phase I/IIa First-in-human, Open-label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of AZD8853 in Participants with Selected Advanced/Metastatic Solid Tumours.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.
    Melero I, de Miguel Luken M, de Velasco G, Garralda E, et al · · 2025 · cited 65× · PMID 39663448 · DOI 10.1038/s41586-024-08305-z
  2. Role of growth differentiation factor 15 in cancer cachexia (Review).
    Ling T, Zhang J, Ding F, Ma L. · · 2023 · cited 45× · PMID 37780545 · DOI 10.3892/ol.2023.14049
  3. Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases.
    Zhang B, Chang JY, Lee MH, Ju SH, et al · · 2024 · cited 23× · PMID 38173375 · DOI 10.4093/dmj.2023.0115
  4. A Comprehensive Review of Immunotherapy Clinical Trials for Metastatic Urothelial Carcinoma: Immune Checkpoint Inhibitors Alone or in Combination, Novel Antibodies, Cellular Therapies, and Vaccines.
    Patel DM, Mateen R, Qaddour N, Carrillo A, et al · · 2024 · cited 13× · PMID 38254823 · DOI 10.3390/cancers16020335
  5. The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy.
    Filippini DM, Romaniello D, Carosi F, Fabbri L, et al · · 2025 · cited 4× · PMID 40868185 · DOI 10.3390/biomedicines13081931
  6. Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy.
    Di Pastena F, Pond G, Tsakiridis EE, Gouveia A, et al · · 2024 · cited 3× · PMID 39511611 · DOI 10.1186/s13014-024-02546-y
  7. First-in-Human Study to Evaluate the Safety and Efficacy of Anti-GDF15 Antibody AZD8853 in Patients with Advanced/Metastatic Solid Tumors.
    Carneiro BA, Gbolahan OB, Abdul Razak AA, Hilton JF, et al · · 2025 · cited 2× · PMID 40354065 · DOI 10.1158/2767-9764.crc-24-0565
  8. New Horizons with Growth Differentiation Factor 15 in Oncology: From Cancer Cachexia and Tumour Immunity to Novel Therapeutic Strategies.
    Sugiyama K, Starling N, Chau I. · · 2025 · PMID 41294666 · DOI 10.3390/curroncol32110604

Verify or expand the search:

Other recruiting trials for Urinary Bladder Neoplasms

Currently open trials in the same condition.

Other AstraZeneca trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT05397171.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing