On July 10, 2023 Exscientia plc (Nasdaq: EXAI) reported that it has enrolled the first patient in its Phase 1/2 "ELUCIDATE" (GTAEXS617-001) study evaluating GTAEXS617 (‘617), Exscientia’s precision-designed CDK7 inhibitor, for the treatment of advanced solid tumours (Press release, Exscientia, JUL 10, 2023, View Source [SID1234633149]). The clinical trial will evaluate the safety, efficacy and pharmacokinetics of ‘617 across multiple ascending doses in patients with advanced solid tumours including head and neck cancer, colorectal cancer, pancreatic cancer, non-small cell lung cancer (NSCLC), HR+/HER2- breast carcinoma and ovarian cancer. ‘617 is a novel CDK7 inhibitor that has been designed by Exscientia in collaboration with GT Apeiron for high potency, selectivity, oral bioavailability and safety.
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"We are excited to begin the clinical evaluation of another AI-designed molecule at Exscientia," said Dr. Michael Krams, Chief Quantitative Medicine Officer at Exscientia. "‘617 was created to solve critical design challenges not met by traditional drug discovery methods with a focus on on-target potency, selectivity and safety. Combined with our unique ability to gather data from primary patient samples to predict response, we believe our ‘617 programme exemplifies the power of the various ways in which we create value through our precision medicine platform. We look forward to enrolling additional patients into the ELUCIDATE trial and anticipate that ‘617, if approved, could meaningfully improve treatment outcomes for patients."
As in Exscientia’s IGNITE trial evaluating its A2AR antagonist, EXS21546, the company used simulation guided clinical trial design to determine the operating characteristics of the two stages of the trial. The dose escalation (Phase 1) portion of the study will characterise the safety profile of ‘617 and establish the recommended Phase 2 dose (RP2D) both as monotherapy and in combination with selected standard of care regimens. The dose expansion (Phase 2) portion of the study will evaluate the preliminary anti-tumour activity of ‘617 as monotherapy and in combination with standard of care.
Exscientia previously highlighted novel ex vivo patient sample response data at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium in October 2022 identifying and confirming CDK7-specific pharmacodynamic biomarkers in cancer and immune cells and identifying high and low responder groups from patient samples across the indications tested ex vivo. Leveraging this translational data has the potential to eventually predict ‘617 treatment response among individual patients, therefore increasing the chances of treatment success. Alongside the evaluation of ‘617 in the ELUCIDATE trial programme, Exscientia and GT Apeiron will also generate data, including clinical endpoints, peripheral and tumour multi-omics, and correlate data and response to previously collected ex vivo results to further support the value of Exscientia’s precision medicine platform.
About the Phase 1/2 ELUCIDATE trial
The ELUCIDATE trial is a multicentre, open-label, two-stage clinical trial to evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of ‘617 administered orally as monotherapy and in combination with standard of care therapies. The company is enrolling patients with solid tumours who have advanced, recurrent or metastatic disease and have failed standard of care.
Both the monotherapy and combination therapy dose escalation portion of the trial will enrol patients across up to seven dose levels, depending on how many dose levels are needed to define the RP2D. The dose expansion phase of the trial will commence upon identification of the RP2D. The primary efficacy endpoint of the expansion phase is objective response rate (ORR).
CDK7 inhibition combines cell cycle disruption with transcription inhibition, making it an attractive target to overcome common resistance pathways in CDK4/6 inhibition, which only targets the cell cycle. ‘617 has the potential to overcome significant safety and efficacy limitations of existing treatments due to its differentiated reversibility and potentially reduced gastrointestinal (GI) toxicity.