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

Study identifier:D9450C00001

ClinicalTrials.gov identifier:NCT05397171

EudraCT identifier:2021-005438-41

CTIS identifier:N/A

Terminated/Withdrawn

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

Medical condition

Urinary Bladder Neoplasms

Phase

Phase 1/2

Healthy volunteers

Study drug

AZD8853, Zirconium-89 crefmirlimab berdoxam

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 07 Jun 2022

Primary Completion Date: 06 Jun 2023

Study Completion Date: 06 Jun 2023

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2024 by AstraZeneca

Collaborators

ImaginAb, Inc.

Inclusion and exclusion criteria

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

No locations available

Arms	Assigned Interventions
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

Documents available

CSR Synopsis
Download
SAP redacted
Download
CSP redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]