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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05397171
• Other study ID #: D9450C00001
• Secondary ID: 2021-005438-41
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 7, 2022
• Est. completion date: June 6, 2023

Study information

• Verified date: July 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: June 6, 2023
• Est. primary completion date: June 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

*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

Related Conditions & MeSH terms

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

Intervention

Drug:
• AZD8853
Monotherapy given until progressive disease or upon meeting other discontinuation criteria.
• Zirconium-89 crefmirlimab berdoxam
CD8+ T cell tracer for positron emission tomography (PET) at two time points in addition to monotherapy AZD8853

Locations

Country	Name	City	State
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Toronto	Ontario
United States	Research Site	Atlanta	Georgia
United States	Research Site	Providence	Rhode Island
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	ImaginAb, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All Substudies-Dose Escalation Parts Only: Number of Dose Limiting Toxicities (DLTs)	Incidence of DLTs during the DLT evaluation period per DLT criteria set forth in the protocol. DLTs are assessed per CTCAE v5.0.	From Cycle 1 Day 1 to end of Cycle 1 (21 days)
Primary	All Substudies: Number of participants with adverse events (AEs)	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.	From Informed Consent through 90 days after the last dose of AZD8853 [about 6 months]
Primary	All Substudies: Number of participants with serious adverse events (SAEs)	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.	From Informed Consent through 90 days after the last dose of AZD8853 [about 6 months]
Primary	All Substudies: Incidence of AEs leading to discontinuation of AZD8853	Assessed per CTCAE v5.0	From Cycle 1 Day 1 through 90 days after the last dose of AZD8853 [about 6 months] [Each cycle is of 21 Days]
Secondary	All Substudies: Overall response rate (ORR) per RECIST 1.1		From Screening through End of Treatment (Approximately 6 months)
Secondary	All Substudies: Disease control rate (DCR) per RECIST 1.1		From Screening through End of Treatment (Approximately 6 months)
Secondary	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)
Secondary	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]
Secondary	All Substudies: Percent change in target lesion tumor size from baseline per RECIST 1.1		From Screening to End of Treatment (Approximately 6 months)
Secondary	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]
Secondary	All Substudies: Change in ctDNA from baseline through post-treatment		Baseline through 90 days after the last dose of study drug (Approximately 9 months)
Secondary	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]
Secondary	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]
Secondary	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]
Secondary	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)
Secondary	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]