a first-in-human study to evaluate the safety and tolerability of azd8853 in participants with selected advanced/metastatic solid tumours

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

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.

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

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