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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05397171
Recruitment Status : Recruiting
First Posted : May 31, 2022
Last Update Posted : August 9, 2022
Sponsor:
Collaborator:
ImaginAb, Inc.
Information provided by (Responsible Party):
AstraZeneca

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
Urinary Bladder Neoplasms Colorectal Cancer Carcinoma, Non-Small-Cell Lung Drug: AZD8853 Drug: Zirconium-89 crefmirlimab berdoxam 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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.
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 : June 7, 2022
Estimated Primary Completion Date : June 20, 2024
Estimated Study Completion Date : June 20, 2024

Resource links provided by the National Library of Medicine


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 Name: 89-Zr-Df-IAB22M2C, 89-Zr-Df-crefmirlimab




Primary Outcome Measures :
  1. All Substudies-Dose Escalation Parts Only: Number of Dose Limiting Toxicities (DLTs) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From Screening through End of Treatment (Approximately 6 months) ]
  2. All Substudies: Disease control rate (DCR) per RECIST 1.1 [ Time Frame: From Screening through End of Treatment (Approximately 6 months) ]
  3. All Substudies: Duration of response (DoR) per RECIST 1.1 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From Screening to End of Treatment (Approximately 6 months) ]
  6. All Substudies: Overall survival (OS) [ Time Frame: 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 [ Time Frame: Baseline through 90 days after the last dose of study drug (Approximately 9 months) ]
  8. All Substudies: Maximum observed serum concentration (Cmax) of AZD885 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Screening and Cycle 2 Day 8 (Approximately 2 months) [Each cycle is of 21 Days] ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

*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

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

*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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05397171


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, Connecticut
Research Site Not yet recruiting
New Haven, Connecticut, United States, 06510
United States, Georgia
Research Site Not yet recruiting
Atlanta, Georgia, United States, 30322
United States, Iowa
Research Site Not yet recruiting
Iowa City, Iowa, United States, 52242
United States, Michigan
Research Site Not yet recruiting
Detroit, Michigan, United States, 48201
United States, Missouri
Research Site Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, Nevada
Research Site Withdrawn
Las Vegas, Nevada, United States, 89169
United States, Rhode Island
Research Site Recruiting
Providence, Rhode Island, United States, 02903
United States, Washington
Research Site Not yet recruiting
Seattle, Washington, United States, 98109
Canada, Ontario
Research Site Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L6
Research Site Not yet recruiting
Toronto, Ontario, Canada, M5G 1X5
France
Research Site Not yet recruiting
Marseille, France, 13015
Research Site Not yet recruiting
Villejuif, France, 94800
United Kingdom
Research Site Not yet recruiting
Cambridge, United Kingdom, CB2 0QQ
Research Site Not yet recruiting
London, United Kingdom, NW3 2QG
Research Site Not yet recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
AstraZeneca
ImaginAb, Inc.
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05397171    
Other Study ID Numbers: D9450C00001
2021-005438-41 ( EudraCT Number )
First Posted: May 31, 2022    Key Record Dates
Last Update Posted: August 9, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.

Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
⁸⁹Zr-Df-IAB22M2C
Zirconium-89 crefmirlimab berdoxam
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
PET
Imaging
CD8 + T cells
Additional relevant MeSH terms:
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Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Urinary Bladder Neoplasms
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases