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Urinary Bladder NeoplasmsPhase 1/2NCT05397171

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

A Phase 1/2 study testing AZD8853 and Zirconium-89 crefmirlimab berdoxam in people with Urinary Bladder Neoplasms and Colorectal Cancer, run by AstraZeneca at 6 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 130 years
What is being tested?
AZD8853 and Zirconium-89 crefmirlimab berdoxam
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
6 sitesin 2 countries
Study dates
7 Jun 2022to 6 Jun 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All Substudies:
  • At least one measurable target lesions per RECIST 1.1.
  • Eastern Cooperative Group (ECOG) of 0-1.
  • Life expectancy of ≥ 12 weeks
  • Adequate organ and marrow function as defined in the protocol
  • Substudy 1:
Show all 12Show fewer
  • Histologically or cytologically confirmed locally advanced, unresectable or metastatic NSCLC, MSS-CRC, or UC.
  • Documented progression from previous therapy
  • NSCLC:
  • 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
  • 4. MSS-CRC: 4.a. At least 2 prior lines of systemic therapy in the advanced / metastatic setting, including specific therapies defined in the protocol
  • 5. UC: 5.a. At least 1 prior line of systemic therapy in the advanced / metastatic setting, including either a platinum-containing regimen and/or an anti-PD-1 or anti-PD-L1 drug 6. Provision of archival tissue or unstained slides 7. Part B: Willing to provide mandatory biposies at screening and on study 8. Part B-CD8+ PET: At least 1 non-liver lesion suitable for PET imaging

Who cannot join

  • All Substudies:
  • Unresolved toxicities ≥ Grade 2 per CTCAE 5.0 from prior therapy, with some exceptions defined in the protocol
  • Symptomatic CNS metastases or leptomeningeal disease
  • Active or ongoing infections, or uncontrolled intercurrent illness as defined in the protocol
  • Active or prior documented autoimmune or inflammatory disorder
  • Body weight loss of > 10% within 30 days of screening visit
Show all 10Show fewer
  • Type 2 diabetes requiring management by metformin, where metformin cannot be switched to another treatment at least 7 days prior to starting study treatment
  • Substudy 1:
  • Must not have had a toxicity from a checkpoint inhibitor that lead to permanent discontinuation of immunotherapy
  • Participants with brain metastases, unless treated, asymptomatic, stable, and not requiring treatment

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States4 sites

  • Research Site

    Atlanta, Georgia, 30322

  • Research Site

    Providence, Rhode Island, 02903

  • Research Site

    Seattle, Washington, 98109

  • Research Site

    St Louis, Missouri, 63110

Other trials in United States

Canada2 sites

  • Research Site

    Ottawa, Ontario, K1H 8L6

  • Research Site

    Toronto, Ontario, M5G 1X5

Other trials in Canada

About this study

Official title: 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

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.

Read the detailed description

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.

Being tested
AZD8853, Zirconium-89 crefmirlimab berdoxam
Keywords
AZD8853, Monoclonal antibody, First-in-Human, Non-Small Cell Lung Cancer, Colorectal cancer, Bladder cancer, Urinary Bladder Neoplasms, Growth Differentiation Factor-15 (GDF-15), CD8-Positive T-Lymphocytes, Urothelial Carcinoma, CD8, ⁸⁹Zr-Df-IAB22M2C, PET, Imaging, CD8 + T cells, Zirconium-89 crefmirlimab berdoxam
Medical subject headings
Urinary Bladder Neoplasms, Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD8853Drug

    Monotherapy given until progressive disease or upon meeting other discontinuation criteria.

  • Zirconium-89 crefmirlimab berdoxamDrug

    Also called 89-Zr-Df-IAB22M2C, 89-Zr-Df-crefmirlimab

    CD8+ T cell tracer for positron emission tomography (PET) at two time points in addition to monotherapy AZD8853

Study groups in NCT05397171
Study groupRoleWhat they receive
Substudy 1 - Parts A, B, and CExperimental* 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
Receives: Drug: AZD8853
Substudy 1 - Parts B1 and B2 with CD8+ PETExperimentalSub-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
Receives: Drug: Zirconium-89 crefmirlimab berdoxam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

Secondary outcomes (13)

  1. 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.

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

  2. 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.

    Measured: 15 weeks

  3. 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.

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

  4. 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.

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

  5. 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.

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

  6. 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.

    Measured: First dose until study end (1 Year)

  7. 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.

    Measured: 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)

  8. 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.

    Measured: 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)

  9. 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.

    Measured: 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)

  10. 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.

    Measured: 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)

  11. 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.

    Measured: 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)

  12. 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.

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

  13. 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

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2022
  2. Study start7 Jun 2022
  3. Primary completion6 Jun 2023
  4. Study completion6 Jun 2023

Why it stopped: This study was terminated early as per protocol Section 4.4, based on overall risk-benefit profile observed to date. No safety concerns reported. Only Substudy 1 Part A was started; Parts B \& C were not started. Entire Master Protocol was terminated.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Substudy 1: * Part A: Part A is an AZD8853 monotherapy dose escalation which may enroll up to 45 participants. * Part B: Dose escalation will be followed by Part B, where up to 40 participants will be enrolled to doses determined to be safe during Part A. Additionally, a sub-set of participants will also receive an investigational radiopharmaceutical, Zirconium-89 crefmirlimab berdoxam, to evaluate the presence of CD8+ T cells in and around cancerous tumours. * Part C: Part C is an efficacy expansion where up to 80 participants may be enrolled based on doses and indications recommended during Part B.
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05397171
Sponsor's protocol ID
D9450C00001
Other IDs
2021-005438-41
Status last verified
Sep 2024
First submitted
24 May 2022
Last updated
1 Oct 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AZD8853 and Zirconium-89 crefmirlimab berdoxam in people with Urinary Bladder Neoplasms and Colorectal Cancer, run by AstraZeneca at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05397171.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.

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