Clinical trial NCT05397171: A First-in-human Study to Evaluate the Safety and Tolerability of AZD8853 in Participants With Selected Advanced/Metastatic Solid Tumours
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: ImaginAb, Inc.
First posted: 2022-05-31
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year)
measure: Number of Participants With Dose Limiting Toxicity (DLT)
timeFrame: From Cycle 1 Day 1 to end of Cycle 1 (21 days)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: First dose until progression of disease (PD) or last evaluable assessment in the absence of progression (1 Year)
measure: Disease Control Rate (DCR) at 15 Weeks
timeFrame: 15 weeks
measure: Duration of Response (DOR)
timeFrame: First documented response until date of first documented disease progression or study end (1 Year)
measure: Progression Free Survival (PFS)
timeFrame: First dose until documented disease progression or study end (1 Year)
measure: Percentage Change From Baseline in Tumor Size
timeFrame: Baseline (pre-treatment) up to Week 6 and Week 15
measure: Overall Survival (OS)
timeFrame: First dose until study end (1 Year)
measure: Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline
timeFrame: Baseline (pre-treatment), Day 8 of Cycle 1, Days 1 and 8 of Cycle 2, Day 1 of Cycles 3, 4, 5, 7 (each cycle is equal to 21 days)
measure: Maximum Observed Concentration (Cmax) of AZD8853
timeFrame: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)
measure: Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853
timeFrame: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)
measure: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 504 Hours Post Dose (AUC[0-504 Hours]) of AZD8853
timeFrame: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)
measure: Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD8853
timeFrame: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)
measure: Number of Participants With Positive Anti-drug Antibody (ADA) of AZD8853
timeFrame: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 year)
measure: Percentage Change From Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels
timeFrame: 0 hours post EOI of Cycle 1 Day 1, Day 1 (Pre-dose) of Cycles 2 and 3 (each cycle equals to 21 days) and 90-days post EOT of 90 days follow-up
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
Study officials:
References: