AI-driven precision medicine company Exscientia has initiated enrollment for its Phase 1/2 “ELUCIDATE” study, marking the first trial of its precision-designed CDK7 inhibitor, GTAEXS617 (‘617), in the treatment of advanced solid tumours.

The trial aims to investigate the safety, efficacy, and pharmacokinetics of GTAEXS617 through multiple ascending doses for 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.

The GTAEXS617 inhibitor, a product of Exscientia’s collaboration with GT Apeiron, has been developed for high potency, selectivity, oral bioavailability, and safety. Like the IGNITE trial examining the A2AR antagonist, EXS21546, the operating characteristics of the ELUCIDATE trial were determined through a simulation-guided clinical trial design.

The trial’s Phase 1 portion will establish the recommended Phase 2 dose (RP2D) and safety profile for GTAEXS617, both as a monotherapy and in combination with selected standard-of-care regimens. The subsequent Phase 2 portion will focus on evaluating the inhibitor’s preliminary anti-tumour activity.

In late 2022, Exscientia presented novel ex vivo patient sample response data at the EORTC-NCI-AACR (ENA) Symposium, which identified and confirmed CDK7-specific pharmacodynamic biomarkers in cancer and immune cells. This data also helped to identify high and low responder groups among patient samples across various ex vivo tested indications. Such translational data could predict individual patients’ response to GTAEXS617 treatment, thereby enhancing chances of successful treatment.

Concurrently with the ELUCIDATE trial, Exscientia and GT Apeiron will generate further data to substantiate the effectiveness of Exscientia’s precision medicine platform.

The ELUCIDATE trial is a multicentre, open-label, two-stage clinical trial. It aims to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of GTAEXS617, administered orally as a monotherapy and in combination with standard-of-care therapies.

The trial will enroll patients with solid tumours who have advanced, recurrent, or metastatic disease and have failed standard of care. The objective response rate (ORR) will serve as the primary efficacy endpoint of the expansion phase.

Dr Michael Krams — Exscientia Chief Quantitative Medicine Officer said: “We are excited to begin the clinical evaluation of another AI-designed molecule 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.”

  CDK7 inhibitor, Colorectal cancer, Dr Michael Krams, Exscientia, GT Apeiron, GTAEXS617, Head and neck cancer, Lung cancer, Non-small cell lung cancer, NSCLC, Ovarian Cancer, Pancreatic Cancer, Small cell lung cancer, Solid tumors, USA