A Phase 1/2 interventional study of AZD8853 and Zirconium-89 crefmirlimab berdoxam in Urinary Bladder Neoplasms, Colorectal Cancer and Carcinoma, Non-Small-Cell Lung, sponsored by AstraZeneca. Terminated at 6 sites in 2 countries. Open to participants aged 18 Years to 130 Years. Per ClinicalTrials.gov, last updated 2024-10-01.
Sponsored by AstraZeneca · Phase 1/2, Interventional, and Treatment
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.
This study is evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AZD8853 in participants with advanced, unresectable or metastatic Non-Small Cell Lung Cancer (NSCLC), Microsatellite Stable Colorectal Cancer (MSS-CRC), Urothelial Carcinoma (UC).
This is a modular study, that includes a master protocol and Substudies.
Substudy 1 will be conducted in 3 parts - Part A: Dose escalation, Part B: Safety expansion and exploratory CD8+ T cell radiopharmaceutical tracer with PET imaging, and Part C: Efficacy expansion.
5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.
This study's enrollment of 17 is below the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
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*Key Inclusion Criteria*
All Substudies:
Substudy 1:
3.a. At least 1 line of systemic therapy in the advanced / metastatic setting 3.b.Must have received anti-PD-1/anti-PD-L1 agent with or without chemotherapy 3.c. Part B and C: Documented no sensitizing EGFR mutations or ALK fusions/rearrangements
*Key Exclusion Criteria*
All Substudies:
Substudy 1:
* Part A: AZD8853 monotherapy dose escalation * Part B1 and Part B2: AZD8853 monotherapy safety expansion at dose levels and indications determined to be safe in Part A * Part C1 and Part C2: AZD8853 monotherapy safety and preliminary efficacy expansion at dose levels and indications determined to be safe in Parts A and B
Drug: AZD8853
Sub-set of participants from Parts B1 and B2 will also receive investigational CD8+ T cell targeted radioactive tracer, Zirconium-89 crefmirlimab berdoxam with PET scans
Drug: Zirconium-89 crefmirlimab berdoxam
Monotherapy given until progressive disease or upon meeting other discontinuation criteria.
CD8+ T cell tracer for positron emission tomography (PET) at two time points in addition to monotherapy AZD8853
Also known as: 89-Zr-Df-IAB22M2C, 89-Zr-Df-crefmirlimab
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year)
Number of Participants With Dose Limiting Toxicity (DLT)
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.
Time frame: From Cycle 1 Day 1 to end of Cycle 1 (21 days)
Objective Response Rate (ORR)
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.
Time frame: First dose until progression of disease (PD) or last evaluable assessment in the absence of progression (1 Year)
Disease Control Rate (DCR) at 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.
Time frame: 15 weeks
Duration of Response (DOR)
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.
Time frame: First documented response until date of first documented disease progression or study end (1 Year)
Progression Free Survival (PFS)
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.
Time frame: First dose until documented disease progression or study end (1 Year)
Percentage Change From Baseline in Tumor Size
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.
Time frame: Baseline (pre-treatment) up to Week 6 and Week 15
Overall Survival (OS)
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.
Time frame: First dose until study end (1 Year)
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline
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.
Time frame: 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)
Maximum Observed Concentration (Cmax) of AZD8853
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.
Time frame: 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)
Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853
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.
Time frame: 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)
Partial Area Under the Plasma Concentration-time Curve From Time 0 to 504 Hours Post Dose (AUC[0-504 Hours]) of AZD8853
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.
Time frame: 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)
Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD8853
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.
Time frame: 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)
Number of Participants With Positive Anti-drug Antibody (ADA) of AZD8853
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.
Time frame: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 year)
Percentage Change From Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels
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
Time frame: 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
This study was conducted from 07 Jun 2022 to 06 Jun 2023 at multiple centers in the United States of America and Canada.
| Milestone | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Started | 3 | 6 | 7 |
| Completed | 0 | 0 | 0 |
| Not completed | 3 | 6 | 7 |
| Withdrew: Death | 2 | 3 | 3 |
| Withdrew: Study terminated by sponsor | 1 | 2 | 3 |
| Withdrew: Withdrawal by subject | 0 | 1 | 1 |
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.
| Participants | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Any AE | 3 | 4 | 6 |
| Any AE possibly related to treatment | 1 | 0 | 2 |
| Any serious adverse event (SAE) | 1 | 3 | 2 |
| Any SAE possibly related to treatment | 0 | 0 | 0 |
| Any SAE with outcome death | 0 | 1 | 0 |
| Any SAE with outcome death and possibly related to treatment | 0 | 0 | 0 |
| Any AE leading to discontinuation of IP | 0 | 1 | 0 |
| Any AE leading to discontinuation of IP and possibly related to treatment | 0 | 0 | 0 |
| Any AE leading to interruption of IP | 0 | 1 | 1 |
| Any SAE leading to discontinuation of IP | 0 | 1 | 0 |
| Any SAE leading to discontinuation of IP and possibly related to treatment (IP) | 0 | 0 | 0 |
| Any AE of greater than or equal to (>=) CTCAE Grade 3 | 1 | 3 | 4 |
| Any AE of >= CTCAE Grade 3 possibly related to treatment | 0 | 0 | 0 |
| Any SAE of >= CTCAE Grade 3 | 1 | 3 | 2 |
| Any SAE of >= CTCAE Grade 3 possibly related to treatment | 0 | 0 | 0 |
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.
| Participants | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Number of Participants With Dose Limiting Toxicity (DLT) | 0 | 0 | 0 |
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.
| Participants | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Objective Response Rate (ORR) | 0 | 0 | 0 |
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.
| Participants | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Disease Control Rate (DCR) at 15 Weeks | 1 | 0 | 1 |
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.
No measurements were reported for this outcome.
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.
| Months | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Progression Free Survival (PFS) | 1.31 (1.18 to 3.38) | 1.23 (1.15 to 3.15) | 1.25 (0.95 to 3.29) |
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.
| Percentage change in tumor size | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Week 6 | 10.1 (-0.9 to 16.7) | 10.9 (-0.9 to 41.4) | 14.9 (1.5 to 37.4) |
| Week 15 | 46.5 (46.5 to 46.5) | 5.7 (5.7 to 5.7) | 70.0 (13.2 to 126.7) |
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.
| Months | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Overall Survival (OS) | 4.47 (2.92 to NA) | 5.45 (2.30 to NA) | NA (0.95 to NA) |
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.
| Percentage change from baseline in ctDNA | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Cycle 1 Day 8 | 74.3700 ± 103.6200 | 30.2546 ± 98.8909 | 10.7795 ± 53.1457 |
| Cycle 2 Day 1 | 92.1105 ± 83.4783 | 32.1430 ± 48.9060 | 20.7386 ± 78.4507 |
| Cycle 2 Day 8 | 101.0003 ± 63.4941 | 84.2143 ± 101.8080 | 116.3071 ± 192.7165 |
| Cycle 3 Day 1 | 64.9807 ± 22.7578 | 131.5277 ± 161.3495 | 26.9231 ± NA |
| Cycle 4 Day 1 | -8.3636 ± NA | 50.2904 ± 54.8320 | 21.4744 ± NA |
| Cycle 5 Day 1 | 64 ± NA | 50.4363 ± NA | — |
| Cycle 7 Day 1 | 67.8182 ± NA | — | — |
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.
| Micrograms per milliliter (ug/mL) | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Maximum Observed Concentration (Cmax) of AZD8853 | 76.70 ± 3.439 | 339.5 ± 96.74 | 1121 ± 225.9 |
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.
| Hours*microgram per milliliter (h*ug/mL) | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853 | 10080 ± 1789 | 49210 ± 12130 | 161100 ± 43070 |
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.
| h*ug/mL | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Partial Area Under the Plasma Concentration-time Curve From Time 0 to 504 Hours Post Dose (AUC[0-504 Hours]) of AZD8853 | 11870 ± 2385 | 57230 ± 14760 | 189400 ± 56040 |
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.
| h*ug/mL | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD8853 | 14580 ± 4136 | 67480 ± 18490 | 223700 ± 79270 |
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.
| Participants | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Number of Participants With Positive Anti-drug Antibody (ADA) of AZD8853 | 1 | 1 | 0 |
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
| Percentage change from baseline in GDF15 | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| Cycle 1 Day 1: 0 hours post EOI | -97.7850 ± 0.1917 | -99.2637 ± 0.1161 | -99.7472 ± NA |
| Cycle 2 Day 1 (Pre-dose) | 324.2284 ± 103.7778 | 411.2175 ± 345.6173 | 165.9668 ± 82.9703 |
| Cycle 3 Day 1 (Pre-dose) | 636.8307 ± NA | 770.4598 ± 520.3336 | 212.5270 ± 111.5861 |
| 90 Days Follow-Up: 90 days post EOT | 2164.2547 ± NA | 1311.2845 ± NA | 2513.913 ± NA |
Collected over From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| AZD8853 300 mg | 2/3 (66.7%) | 2/3 (66.7%) | 3/3 (100%) |
| AZD8853 1000 mg | 3/6 (50%) | 3/6 (50%) | 4/6 (66.7%) |
| AZD8853 3000 mg | 3/7 (42.9%) | 2/7 (28.6%) | 6/7 (85.7%) |
| Event | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| SyncopeVascular disorders | 1/3 | 0/6 | 0/7 |
| COVID-19Infections and infestations | 1/3 | 0/6 | 0/7 |
| Clostridium difficile infectionInfections and infestations | 1/3 | 0/6 | 0/7 |
| Anal fistulaGastrointestinal disorders | 1/3 | 0/6 | 0/7 |
| SepsisInfections and infestations | 1/3 | 0/6 | 0/7 |
| Blood bilirubin increasedInvestigations | 0/3 | 1/6 | 0/7 |
| EmbolismVascular disorders | 0/3 | 1/6 | 0/7 |
| Cardiac arrestCardiac disorders | 0/3 | 1/6 | 0/7 |
| Back painMusculoskeletal and connective tissue disorders | 0/3 | 1/6 | 0/7 |
| Small intestinal obstructionGastrointestinal disorders | 0/3 | 0/6 | 1/7 |
| Event | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg |
|---|---|---|---|
| PyrexiaGeneral disorders | 2/3 | 0/6 | 1/7 |
| Decreased appetiteMetabolism and nutrition disorders | 2/3 | 0/6 | 2/7 |
| DiarrhoeaGastrointestinal disorders | 1/3 | 1/6 | 3/7 |
| Abdominal painGastrointestinal disorders | 1/3 | 1/6 | 3/7 |
| Muscular weaknessMusculoskeletal and connective tissue disorders | 1/3 | 0/6 | 0/7 |
| Blood alkaline phosphatase increasedInvestigations | 1/3 | 0/6 | 0/7 |
| AnaemiaBlood and lymphatic system disorders | 1/3 | 0/6 | 0/7 |
| DehydrationMetabolism and nutrition disorders | 1/3 | 0/6 | 0/7 |
| HypotensionVascular disorders | 1/3 | 0/6 | 0/7 |
| HyponatraemiaMetabolism and nutrition disorders | 1/3 | 0/6 | 0/7 |
Safety set included all participants who received any amount of investigational product (IP).
| Age, Continuous(Years) | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg | Total |
|---|---|---|---|---|
| Mean | 62.0 ± 13.2 | 62.8 ± 4.2 | 65.1 ± 7.4 | 63.7 ± 7.3 |
| Sex: Female, Male(Participants) | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg | Total |
|---|---|---|---|---|
| Female | NA | 2 | 3 | NA |
| Male | NA | 4 | 4 | NA |
| Race/Ethnicity, Customized(Participants) | AZD8853 300 mg | AZD8853 1000 mg | AZD8853 3000 mg | Total |
|---|---|---|---|---|
| White | 3 | 5 | 5 | 13 |
| Not reported | 0 | 1 | 1 | 2 |
| Other | 0 | 0 | 1 | 1 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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