Trials / Recruiting

RecruitingNCT05944237

HTL0039732 in Participants With Advanced Solid Tumours

A Cancer Research UK Phase I/IIa Trial of HTL0039732, Given Orally as Monotherapy and in Combination With Immunotherapy or Other Approved Therapies in Participants With Advanced Solid Tumours

Status: Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 150 (estimated)

Sponsor: Cancer Research UK · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

The purpose of this trial is to evaluate a new drug, HTL0039732, that will be administered on its own (as a monotherapy) and in combination with atezolizumab or with other approved anti-cancer therapies, in participants with advanced solid tumours.

Detailed description

The trial will investigate HTL0039732, a novel specific E-type prostanoid receptor 4 (EP4) antagonist, as a monotherapy and in combination with atezolizumab, a monoclonal antibody that binds to the programmed death ligand 1 (PD-L1). The trial may be expanded in future to also evaluate HTL0039732 in combination with other approved anti-cancer therapies. HTL0039732 is a small molecule drug that blocks activation of EP4 receptors by prostaglandin E2 (PGE2), a naturally occurring substance in the body. Prostaglandin E2 may be elevated in cancer and signalling via the EP4 receptor can lead to suppression of immune activity, allowing the cancer to escape from the immune system. Blocking the EP4 receptor may relieve that immunosuppression, allowing the immune system to be active against the cancer again. Atezolizumab is an established immune checkpoint inhibitor that overcomes a key immunosuppressive signal and improves the magnitude and quality of tumour-specific T-cell responses, resulting in improved anti-cancer activity. It, and other similar agents, are approved for the treatment of several different types of cancer. As a common mechanism of immune suppression, immune checkpoint inhibitors also have a role in combination immunotherapies and combining EP4 inhibition by HTL0039732 with PD-L1 blockade by atezolizumab, is expected to have increased activity. The trial will investigate HTL0039732 as a monotherapy and in combination with atezolizumab, and potentially with other approved anti-cancer therapies, in participants with advanced solid tumours (Phase 1 Part A) and in participants with advanced solid tumours where PGE2/EP4 signalling is believed to be more prevalent or significant (Phase 1 Part B and Phase 2a). This is a first-in-human clinical trial and is split as follows: * Phase 1 is the 'dose escalation' phase, where two groups (known as Part A and Part B) of participants with solid tumours will receive increasing doses of HTL0039732 to find the safest dose. * Part A participants will receive HTL0039732 as a single agent. * Part B participants will receive HTL0039732 in combination with atezolizumab. * More Parts may be added in future for participants to receive HTL0039732 in combination with other approved anti-cancer therapies. * Phase 2a is the 'dose expansion' phase, where participants grouped according to the type of cancer they have will receive the recommended Phase 2 dose (RP2D) of HTL0039732 in combination with atezolizumab, and potentially in combination with other approved anti-cancer therapies. Phase 2a will follow a response enrichment approach; activity of the investigational medicinal products will be assessed in each group and ongoing recruitment will focus on tumour types with promising signals. The main aims of the clinical trial are to find out: * The most appropriate dose of HTL0039732 administered on its own, and the most appropriate dose/s of HTL0039732 to take forward for further investigation in combination with atezolizumab and with other approved anti-cancer therapies. * More about any potential side effects of HTL0039732 when given alone and in combination with atezolizumab and other approved anti-cancer therapies.

Conditions

Interventions

Type	Name	Description
DRUG	HTL0039732 Capsules	HTL0039732 Capsules will be administered orally to fasted participants, although an exploration of food effects may be performed as a single dose at Cycle 0. A single dose will be administered between 3 and 9 days prior to commencement of Cycle 1. From Cycle 1 Day 1, HTL0039732 will be administered on a once daily (QD) schedule. Each administration cycle will consist of 21 days with no break between cycles. Participants may initially receive up to 18 cycles but may continue for a further 18 cycles if they are deemed to be benefitting.
DRUG	HTL0039732 Capsules and atezolizumab infusion	HTL0039732 Capsules will be administered orally on a QD schedule to participants starting on Cycle 1 Day 1. Each administration cycle will consist of 21 days with no break between cycles. Participants will also receive 1200 mg atezolizumab as an IV infusion on Day1 of each cycle (i.e. every 3 weeks). Participants may initially receive up to 18 cycles of HTL0039732 but may continue for a further 18 cycles if they are deemed to be benefitting, and they may receive up to 36 cycles of atezolizumab.

Timeline

Start date: 2023-07-13
Primary completion: 2027-06-01
Completion: 2027-06-01
First posted: 2023-07-13
Last updated: 2025-06-08

Locations

5 sites across 1 country: United Kingdom

Source: ClinicalTrials.gov record NCT05944237. Inclusion in this directory is not an endorsement.