ONA-255

Table of contents

• What is ONA-255?
• How does ONA-255 work?
• Which conditions is ONA-255 studied for?
• How is ONA-255 given?
• What do the clinical trials show?
• What side effects are known?

What is ONA-255?

ONA-255 is a protein-based substance that is still investigational, meaning it has not received marketing authorisation and is not yet approved as a medicine.^[1] The substance is developed by ONA Therapeutics S.L.^[1] It is classified in the therapeutic area of neoplasms, which covers cancers.^[1] In the registered trial, ONA-255 is given as a single agent, which means it is being tested on its own rather than in combination with other cancer treatments.^[1]

How does ONA-255 work?

The registered trial does not describe the molecular target of ONA-255. What is known from the trial record is that the researchers use two types of biological response to judge whether the drug is active: a decline in circulating tumour DNA (ctDNA) or a shrinkage of tumours measured by imaging according to RECIST criteria.^[1] The trial aims to find the minimum dose at which one of these biological responses occurs, called the minimum biological active dose (MBAD).^[1]

Which conditions is ONA-255 studied for?

The registered trial studies ONA-255 in people with advanced cancer. The trial lists three groups of conditions:

• Advanced cancer – cancer that has spread or is no longer curable by local treatments alone.
• Breast cancer – specifically hormone receptor-positive, HER2-negative advanced breast cancer in the dose-optimisation part of the trial.
• Metastatic gastric / gastroesophageal junction cancer – cancer of the stomach or the area where the stomach meets the oesophagus that has spread to other parts of the body.

How is ONA-255 given?

ONA-255 is prepared as a solution for infusion and is given by intravenous infusion, which means it is delivered directly into a vein over a period of time.^[1] The trial record does not report the dose or the length of each infusion.^[1]

What do the clinical trials show?

There is one registered clinical trial of ONA-255. It is a Phase 1/2 study with a planned enrolment of 117 participants, and its status is authorised, meaning it has received the necessary approvals and may proceed.^[1] The trial is divided into three parts:

• Phase 1a – determines the minimum biological active dose (MBAD) and the maximum tolerated dose (MTD) of ONA-255 as a single agent.
• Phase 1b – determines the optimal dose and the recommended Phase 2 dose (RP2D) in hormone receptor-positive, HER2-negative advanced breast cancer, and, if applicable, in metastatic gastric or gastroesophageal junction cancer.
• Phase 2a – assesses the preliminary overall response rate of ONA-255 at the recommended Phase 2 dose.

The main measures in the trial include the number of participants who experience dose-limiting toxicities during the first 21-day cycle, safety and tolerability assessed through treatment-related adverse events, drug interruptions, dose reductions and treatment discontinuations, and the investigator-assessed overall response rate defined as the proportion of participants with a complete or partial tumour response according to RECIST version 1.1.^[1]

What side effects are known?

No side effects of ONA-255 are reported in the available sources. The registered trial is designed to measure side effects, including dose-limiting toxicities, treatment-related adverse events and serious adverse events, but no results are yet available.^[1]