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

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05397171
Collaborator
ImaginAb, Inc. (Industry)
165
Enrollment
15
Locations
2
Arms
24.4
Anticipated Duration (Months)
11
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
165 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention 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.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)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 7, 2022
Anticipated Primary Completion Date :
Jun 20, 2024
Anticipated Study Completion Date :
Jun 20, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Substudy 1 - Parts A, B, and C

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
Monotherapy given until progressive disease or upon meeting other discontinuation criteria.
Experimental: Substudy 1 - Parts B1 and B2 with CD8+ PET

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
CD8+ T cell tracer for positron emission tomography (PET) at two time points in addition to monotherapy AZD8853
Other Names:
  • 89-Zr-Df-IAB22M2C, 89-Zr-Df-crefmirlimab

    		•

    Outcome Measures

    Primary Outcome Measures

    1. All Substudies-Dose Escalation Parts Only: Number of Dose Limiting Toxicities (DLTs) [From Cycle 1 Day 1 to end of Cycle 1 (21 days)]

      Incidence of DLTs during the DLT evaluation period per DLT criteria set forth in the protocol. DLTs are assessed per CTCAE v5.0.

    2. All Substudies: Number of participants with adverse events (AEs) [From Informed Consent through 90 days after the last dose of AZD8853 [about 6 months]]

      Incidence of AEs by evaluation of clinically significant changes from baseline in clinical laboratory parameters, vital signs, ECG results, and other clinical assessments per CTCAE 5.0.

    3. All Substudies: Number of participants with serious adverse events (SAEs) [From Informed Consent through 90 days after the last dose of AZD8853 [about 6 months]]

      Incidence of SAEs by evaluation of clinically significant changes from baseline in clinical laboratory parameters, vital signs, ECG results, and other clinical assessments per CTCAE 5.0.

    4. All Substudies: Incidence of AEs leading to discontinuation of AZD8853 [From Cycle 1 Day 1 through 90 days after the last dose of AZD8853 [about 6 months] [Each cycle is of 21 Days]]

      Assessed per CTCAE v5.0

    Secondary Outcome Measures

    1. All Substudies: Overall response rate (ORR) per RECIST 1.1 [From Screening through End of Treatment (Approximately 6 months)]

    2. All Substudies: Disease control rate (DCR) per RECIST 1.1 [From Screening through End of Treatment (Approximately 6 months)]

    3. All Substudies: Duration of response (DoR) per RECIST 1.1 [From first documented response to Disease Progression or other End of Study criteria are met (Approximately 1 year)]

    4. All Substudies: Progression Free Survival (PFS) per RECIST 1.1 [From Cycle 1 Day 1 through Disease Progression or other End of Study qualifying event occurs (Approximately 1 year) [Each cycle is of 21 Days]]

    5. All Substudies: Percent change in target lesion tumor size from baseline per RECIST 1.1 [From Screening to End of Treatment (Approximately 6 months)]

    6. All Substudies: Overall survival (OS) [From Cycle 1 Day 1 until Death or End of Study (Approximately 2 years) [Each cycle is of 21 days]]

    7. All Substudies: Change in ctDNA from baseline through post-treatment [Baseline through 90 days after the last dose of study drug (Approximately 9 months)]

    8. All Substudies: Maximum observed serum concentration (Cmax) of AZD885 [From Cycle 1 Day 1 through 90 days after the last dose of study drug (Approximately 9 months) [Each cycle is of 21 Days]]

    9. All Substudies: Area Under the Curve (AUC) of AZD8853 [From Cycle 1 Day 1 through 90 days after the last dose of study drug (Approximately 9 months) [Each cycle is of 21 Days]]

    10. All Substudies: Number and percentage of participants with detectable antidrug antibodies (ADAs) against AZD8853 [From Cycle 1 Day 1 through 90 days after the last dose (Approximately 9 months) [Each cycle is of 21 Days]]

    11. Substudy 1-Parts A & B: Change in circulating GDF15 serum levels [Screening through 90 days after the last dose of study drug (Approximately 9 months)]

    12. Substudy 1 - Part B: Change in CD8 tumor infiltration in paired biopsies [Screening and Cycle 2 Day 8 (Approximately 2 months) [Each cycle is of 21 Days]]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Key Inclusion Criteria

    All Substudies:

    1. At least one measurable target lesions per RECIST 1.1.

    2. Eastern Cooperative Group (ECOG) of 0-1.

    3. Life expectancy of ≥ 12 weeks

    4. Adequate organ and marrow function as defined in the protocol

    Substudy 1:

    1. Histologically or cytologically confirmed locally advanced, unresectable or metastatic NSCLC, MSS-CRC, or UC.

    2. Documented progression from previous therapy

    3. 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

    1. MSS-CRC: 4.a. At least 2 prior lines of systemic therapy in the advanced / metastatic setting, including specific therapies defined in the protocol

    2. 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

    Key Exclusion Criteria

    All Substudies:

    1. Unresolved toxicities ≥ Grade 2 per CTCAE 5.0 from prior therapy, with some exceptions defined in the protocol

    2. Symptomatic CNS metastases or leptomeningeal disease

    3. Active or ongoing infections, or uncontrolled intercurrent illness as defined in the protocol

    4. Active or prior documented autoimmune or inflammatory disorder

    5. Body weight loss of > 10% within 30 days of screening visit

    6. 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:

    1. Must not have had a toxicity from a checkpoint inhibitor that lead to permanent discontinuation of immunotherapy

    2. Participants with brain metastases, unless treated, asymptomatic, stable, and not requiring treatment

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site New Haven Connecticut United States 06510
    2 Research Site Atlanta Georgia United States 30322
    3 Research Site Iowa City Iowa United States 52242
    4 Research Site Detroit Michigan United States 48201
    5 Research Site Saint Louis Missouri United States 63110
    6 Research Site Las Vegas Nevada United States 89169
    7 Research Site Providence Rhode Island United States 02903
    8 Research Site Seattle Washington United States 98109
    9 Research Site Ottawa Ontario Canada K1H 8L6
    10 Research Site Toronto Ontario Canada M5G 1X5
    11 Research Site Marseille France 13015
    12 Research Site Villejuif France 94800
    13 Research Site Cambridge United Kingdom CB2 0QQ
    14 Research Site London United Kingdom NW3 2QG
    15 Research Site Newcastle Upon Tyne United Kingdom NE7 7DN

    Sponsors and Collaborators

    • AstraZeneca
    • ImaginAb, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT05397171
    Other Study ID Numbers:
    • D9450C00001
    • 2021-005438-41
    First Posted:
    May 31, 2022
    Last Update Posted:
    Aug 9, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    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
    Additional relevant MeSH terms:
    Colorectal Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Urinary Bladder Neoplasms

    Study Results

    No Results Posted as of Aug 9, 2022