NCT05397171 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: TERMINATED
Registry last update: 2024-10-01

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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outcome · POSTED

Number of Participants With Dose Limiting Toxicity (DLT)

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outcome · POSTED

Objective Response Rate (ORR)

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outcome · POSTED

Disease Control Rate (DCR) at 15 Weeks

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Percentage Change From Baseline in Tumor Size

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline

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outcome · POSTED

Maximum Observed Concentration (Cmax) of AZD8853

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outcome · POSTED

Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853

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outcome · POSTED

Partial Area Under the Plasma Concentration-time Curve From Time 0 to 504 Hours Post Dose (AUC[0-504 Hours]) of AZD8853

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outcome · POSTED

Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD8853

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outcome · POSTED

Number of Participants With Positive Anti-drug Antibody (ADA) of AZD8853

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outcome · POSTED

Percentage Change From Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
* 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
intervention Names
Drug: AZD8853
label
Substudy 1 - Parts A, B, and C
type
EXPERIMENTAL
description
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
intervention Names
Drug: Zirconium-89 crefmirlimab berdoxam
label
Substudy 1 - Parts B1 and B2 with CD8+ PET
type
EXPERIMENTAL

interventions

arm Group Labels
Substudy 1 - Parts A, B, and C
description
Monotherapy given until progressive disease or upon meeting other discontinuation criteria.
name
AZD8853
type
DRUG
arm Group Labels
Substudy 1 - Parts B1 and B2 with CD8+ PET
description
CD8+ T cell tracer for positron emission tomography (PET) at two time points in addition to monotherapy AZD8853
name
Zirconium-89 crefmirlimab berdoxam
other Names
89-Zr-Df-IAB22M2C, 89-Zr-Df-crefmirlimab
type
DRUG

Study design

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.

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 17
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
time Frame
From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year)
description
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.
measure
Number of Participants With Dose Limiting Toxicity (DLT)
time Frame
From Cycle 1 Day 1 to end of Cycle 1 (21 days)

secondary Outcomes

description
ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). This outcome measure was assessed only for substudy 1 Part A.
measure
Objective Response Rate (ORR)
time Frame
First dose until progression of disease (PD) or last evaluable assessment in the absence of progression (1 Year)
description
Disease control was defined as a best overall response (BOR) of confirmed CR or PR or having stable disease (SD) (without subsequent cancer therapy) maintained for greater than or equal to (\>=) 14 weeks (study week 15) from first IP. Disease control rate at study week 15 weeks (DCR-15) was defined as the percentage of participants who had disease control at study week 15 weeks. This outcome measure was assessed only for substudy 1 Part A.
measure
Disease Control Rate (DCR) at 15 Weeks
time Frame
15 weeks
description
The DOR was defined as the time from the date of first documented response (which was subsequently confirmed) until the date of documented progression or death in the absence of disease progression. This outcome measure was assessed only for substudy 1 Part A.
measure
Duration of Response (DOR)
time Frame
First documented response until date of first documented disease progression or study end (1 Year)
description
The PFS was defined as the time from the start of study intervention until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from study intervention or received another anti-cancer therapy prior to progression. This outcome measure was assessed only for substudy 1 Part A.
measure
Progression Free Survival (PFS)
time Frame
First dose until documented disease progression or study end (1 Year)
description
Tumor size was the sum of the longest diameters (or short axis measurements for lymph nodes) of the target lesions (TLs). Percentage change in tumor size was determined for participants with measurable disease at baseline. Baseline for Response evaluation criteria in solid tumors (RECIST) version 1.1 was defined as the last evaluable assessment prior to first IP dose. This outcome measure was assessed only for substudy 1 Part A.
measure
Percentage Change From Baseline in Tumor Size
time Frame
Baseline (pre-treatment) up to Week 6 and Week 15
description
Overall survival was defined as the time from the start of treatment until death due to any cause. This outcome measure was assessed only for substudy 1 Part A.
measure
Overall Survival (OS)
time Frame
First dose until study end (1 Year)
description
Change in ctDNA is defined as the percentage change in ctDNA from baseline to each timepoint for the safety population. This outcome measure was assessed only for substudy 1 Part A.
measure
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline
time Frame
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)
description
The pharmacokinetic (PK) (Cmax) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
measure
Maximum Observed Concentration (Cmax) of AZD8853
time Frame
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)
description
The PK (AUClast) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
measure
Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853
time Frame
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)
description
The PK (AUC\[t1-t2\]) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
measure
Partial Area Under the Plasma Concentration-time Curve From Time 0 to 504 Hours Post Dose (AUC[0-504 Hours]) of AZD8853
time Frame
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)
description
The PK (AUCinf) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
measure
Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD8853
time Frame
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)
description
The immunogenicity of AZD8853 in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
measure
Number of Participants With Positive Anti-drug Antibody (ADA) of AZD8853
time Frame
From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 year)

Full study description

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.

Source references