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

NCT05397171 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: D9450C000012021-005438-41
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 6

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.

Conditions

Urinary Bladder Neoplasms; Colorectal Cancer; Carcinoma, Non-Small-Cell Lung

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

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

Secondary Outcomes (13)

• Objective Response Rate (ORR)

  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

  15 weeks

• Duration of Response (DOR)

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

• Progression Free Survival (PFS)

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

• Percentage Change From Baseline in Tumor Size

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

Study Arms (2)

Substudy 1 - Parts A, B, and C

EXPERIMENTAL

* 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

Substudy 1 - Parts B1 and B2 with CD8+ PET

EXPERIMENTAL

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

Interventions

AZD8853 DRUG

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

Substudy 1 - Parts A, B, and C

Zirconium-89 crefmirlimab berdoxam DRUG

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

Substudy 1 - Parts B1 and B2 with CD8+ PET

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Histologically or cytologically confirmed locally advanced, unresectable or metastatic NSCLC, MSS-CRC, or UC.
• Documented progression from previous therapy
• NSCLC:
• 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
• \. MSS-CRC: 4.a. At least 2 prior lines of systemic therapy in the advanced / metastatic setting, including specific therapies defined in the protocol
• \. 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AstraZeneca: lead
• ImaginAb, Inc.: collaborator

Study Sites (6)

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Providence, Rhode Island, 02903, United States

Location

Research Site

Seattle, Washington, 98109, United States

Location

Research Site

Ottawa, Ontario, K1H 8L6, Canada

Location

Research Site

Toronto, Ontario, M5G 1X5, Canada

Location

Related Links

• CSR Synopsis
• SAP redacted
• CSP redacted

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; 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; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Limitations and Caveats

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 Sub-study 1 Part A was started; Parts B \& C were not started.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 24, 2022
• First Posted: May 31, 2022
• Study Start: June 7, 2022
• Primary Completion: June 6, 2023
• Study Completion: June 6, 2023
• Last Updated: October 1, 2024
• Results First Posted: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

US (4); CA (2)