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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Monotherapy given until progressive disease or upon meeting other discontinuation criteria.
CD8+ T cell tracer for positron emission tomography (PET) at two time points in addition to monotherapy AZD8853
Research Site
Atlanta, Georgia, United States
Research Site
St Louis, Missouri, United States
Research Site
Providence, Rhode Island, United States
Research Site
Seattle, Washington, United States
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.
Time frame: 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.
Time frame: From Cycle 1 Day 1 to end of Cycle 1 (21 days)
Objective Response Rate (ORR)
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.
Time frame: 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
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.
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Research Site
Ottawa, Ontario, Canada
Research Site
Toronto, Ontario, Canada
Time frame: 15 weeks
Duration of Response (DOR)
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.
Time frame: First documented response until date of first documented disease progression or study end (1 Year)
Progression Free Survival (PFS)
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.
Time frame: First dose until documented disease progression or study end (1 Year)
Percentage Change From Baseline in Tumor Size
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.
Time frame: Baseline (pre-treatment) up to Week 6 and Week 15
Overall Survival (OS)
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.
Time frame: First dose until study end (1 Year)
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels From Baseline
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.
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)
Maximum Observed Concentration (Cmax) of AZD8853
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.
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)
Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853
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.
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)
Partial Area Under the Plasma Concentration-time Curve From Time 0 to 504 Hours Post Dose (AUC[0-504 Hours]) of AZD8853
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.
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)
Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD8853
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.
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)
Number of Participants With Positive Anti-drug Antibody (ADA) of AZD8853
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.
Time frame: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 year)
Percentage Change From Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels
The pharmacodynamics (PD) activity of AZD8853 by assessment of candidate biomarkers in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy1 Part A. End of infusion= EOI; End of treatment= EOT
Time frame: 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