ADME and ABA trial in solid tumor patients

ICON partnered with a global pharmaceutical sponsor to deliver a highly complex phase 1 ADME and absolute bioavailability study for a small‑molecule oncology therapy. Strict eligibility requirements, challenging patient identification, and a radiolabeled investigational product with a 72‑hour shelf life created significant operational hurdles. Leveraging strong relationships with an expert oncologist, ICON provided a fully integrated single‑site solution - including its clinical research unit in Hungary and GMP and bioanalytical laboratories in the Netherlands - ensuring efficient patient screening, precise drug handling, and successful execution. The study generated the critical mass balance and pharmacokinetic data required to progress the therapy to its next regulatory milestone.

This open‑label, phase 1 study was designed to generate critical ADME and absolute oral bioavailability (ABA) data for a tumor‑targeting agent that activates p53 to induce cell‑cycle arrest or apoptosis in cancer cells. The challenge was to characterise the drug’s pharmacokinetic profile in patients with advanced solid tumors. To achieve this, patients were enrolled into either an ADME or an ABA cohort based on the timing of their entry into the study, with each assessment requiring a single administration of a radiolabeled dose (¹⁴C) during cycle 1.

This study presented some key challenges:

Strict eligibility criteria for enrolment

There were strict eligibility criteria for the identification and recruitment of participants which made screening particularly complex for this study. Participants had to have failed, been rejected, or deemed ineligible for conventional treatment options. They also had to fulfil multiple clinical, functional and safety-related criteria including: 

• A histologically or cytologically confirmed diagnosis of an advanced, unresectable, or metastatic solid tumor with potential expected benefit from treatment. (known p53 mutation was an exclusion)
• Adequate organ function 
• No significant gastric conditions—whether resulting from oncologic history, prior medical issues, or surgical interventions—that could affect adherence to study requirements or interfere with drug absorption or evaluation
• Maintain an ECOG performance status of 0 or 1

Limited shelf life of drug product

Beyond the challenges of identifying and enrolling eligible participants, the study was further complicated by the treatment’s 72-hour shelf life. Manufacturing and delivery schedules of both the oral and intravenous ¹⁴C compounds had to be precisely coordinated so they would arrive at the investigation site in time for participants to receive their doses.

ICON engaged a highly experienced oncologist with extensive clinical trial expertise and access to a large patient population, inviting them to serve as the study’s Principal Investigator (PI). The PI identified suitable candidates and referred interested individuals to ICON’s phase 1 clinical research unit in Budapest. 

Following a thorough screening procedure, eligible patients were confined and received the single dose. In the ADME part, blood, urine, feces, and vomitus (when applicable) were collected. ADME release criteria were met by day 15 in most cases. If the release criteria were not met by day 15, patients were readmitted to the trial site for additional 24‑hour urine and feces collection intervals.

During the ABA assessment, the plasma exposure of the intravenous ¹⁴C microdose was compared with the exposure of the oral dose.  Upon completion of the ADME or ABA part during cycle 1, all patients who did not meet discontinuation criteria (including disease progression or unacceptable toxicity) continued to receive treatment for as long as they were deriving clinical benefit. 

ICON applied its extensive expertise in managing radiolabeled study drugs (^¹⁴C and ^¹³C) to support this study. The GMP‑certified laboratory in the Netherlands manufactured the small‑molecule investigational product and coordinated shipment to Budapest, ensuring adherence to the treatment’s strict 72‑hour shelf‑life limit. In parallel with manufacturing, all release documentation was prepared in advance to eliminate the risk of delays. Once the shipment arrived in Budapest, the onsite pharmacist completed all required monitoring and quality checks before the drug was administered to participants at the clinical site.

A total of 19 patients were screened, with six enrolled in the ADME cohort, seven in the ABA cohort, and six excluded. The 60% failure rate was low given the particularly stringent patient criteria and complex screening requirements for this study.