HTL0039732 in Participants With Advanced Solid Tumours

Recruiting now · Phase 1/Phase 2

Conditions studied: Neoplasms, Prostatic Neoplasms, Castration-Resistant, Stomach Neoplasms, Esophageal Neoplasms, Head and Neck Neoplasms, Colorectal Neoplasms, Pancreatic Neoplasms, Lung Neoplasms, Urinary Bladder Neoplasms, Mesothelioma, Malignant, Uterine Cervical Neoplasms, Kidney Neoplasms, Sarcoma, Pheochromocytomas

In brief

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.

Key facts

Study ID: NCT05944237
Run by: Cancer Research UK
People needed: 150
Starts: 2023-07-13
Expected to finish: 2027-06-01
Last updated by the study team: 2025-06-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Written (signed and dated) informed consent and capable of co-operating with investigational medicinal product administration and follow-up.
Phase 1, dose escalation phase
Part A (HTL0039732 monotherapy):
Histologically or cytologically proven advanced solid tumour, refractory to conventional treatment, or for which no further conventional therapy is considered appropriate by the Investigator or is declined by the potential participant.
At least 1 measurable lesion according to RECIST v1.1, which (in the Investigator's opinion) has had objective radiological progression on or after the last therapy, or at least one assessable lesion e.g. pleural or peritoneal thickening that does not fulfil RECIST v1.1 criteria for measurable disease.
a. Consent for fresh tumour biopsy sample(s) at time of PD, if the participant has accessible disease and is eligible to receive atezolizumab. Optional at time of disease progression.
Consent to access and analysis of any available archival tissue or a fresh tumour sample at baseline, if archival tissue is unavailable.
Consent for fresh tumour biopsy sample(s) at time of PD, if the participant has accessible disease and is eligible to receive atezolizumab. Optional at time of disease progression.
Phase 1 Part B:
Histologically proven advanced solid tumour where PGE2/EP4 signalling is believed to be more prevalent or significant (such as microsatellite stable colorectal cancer (MSS CRC), gastro-esophageal cancer, head and neck squamous cell carcinoma (HNSCC), mCRPC, pancreatic cancer, lung cancer, bladder cancer, mesothelioma, cervical cancer, renal cancer, sarcoma, pheochromocytoma and cancers with PI3K/AKT/mTOR pathway activating mutations using a clinically-validated assay).
Phase 2a:
Histologically proven advanced solid tumour, in line with indications listed below, refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the potential participant:
MSS CRC with PIK3CA or HER2 mutation, and/or other driver mutation as agreed with the Sponsor (genomic alteration to have been previously identified using a validated next-generation sequencing method performed on either tumour tissue or circulating tumour DNA [ctDNA]);
Gastric or gastroesophageal junction (GOJ) adenocarcinoma;
Clear cell renal cell carcinoma;
mCRPC
Phase 1 Part B and Phase 2a:
Consent to access and analysis of any available archival tissue.
Consent for fresh tumour biopsy samples at baseline and on treatment. However, the following exceptions will be permitted if archival tissue is available at the recruiting site:
Patients with mCRPC: biopsies are not required for those whose only safely accessible lesions are bone metastases that lack an accessible soft tissue component.
For the first 12 participants in each indication: the on-trial biopsy is optional; and the baseline biopsy is mandatory if there is a safely accessible lesion but may be omitted for patients who have no safely accessible lesion, to permit their inclusion in the study. This will continually be assessed through the study.
Disease refractory to conventional treatment, or for which no further conventional therapy is considered appropriate by the Investigator or is declined by the participant.
Except for mCRPC, at least 1 measurable lesion according to RECIST v1.1, which (in the Investigator's opinion) has had objective radiological progression on or after the last therapy. Potential participants with mCRPC may instead have had PD according to PCWG3 criteria.
Previously irradiated lesions cannot be counted as target lesions unless clearly progressed after the radiotherapy.
Lesions that are intended to be biopsied should not be counted as target lesions (those undergoing biopsy must have at least one target lesion that is not intended to be biopsied).

You may not qualify if…

Radiotherapy (except for palliative reasons), chemotherapy, non chemotherapy systemic anti-cancer therapy (apart from life-long hormone suppression such as luteinising hormone-releasing agents in participants with mCRPC) or investigational medicinal products during the 4 weeks prior to enrolment; or first dose of an immunotherapy during the previous 12 weeks before first dose of HTL0039732.
Ongoing toxic manifestations of previous treatments that are Grade >1 per CTCAE v5.0.
Any central nervous system metastases (unless potential participants have had local therapy and are asymptomatic, radiologically stable and have been off steroids for ≥4 weeks prior to enrolment).
Women of child-bearing potential (or who are already pregnant or lactating). Exceptions apply.
Men with partners of childbearing potential. Exceptions apply.
Major thoracic or abdominal surgery from which the potential participant has not yet recovered.
At high medical risk because of non-malignant systemic disease, including active uncontrolled infection.
Known history of current or latent tuberculosis, HIV or Hepatitis B or C infection.
Prior treatment with EP4 inhibitor.
Treatment with selective cyclooxygenase-2 inhibitor in the 8 weeks prior to enrolment.
Known hypersensitivity or intolerance to hydroxypropyl methylcellulose.
Use of systemic immunosuppressive agent in the 2 weeks prior to enrolment. Exceptions apply.
Significant cardiovascular disease.
Known active peptic ulcer disease, or symptoms of gastritis, dyspepsia or gastro-esophageal reflux disease (one or more episodes per week).
Current or planned participation in another interventional clinical trial, whilst taking part in this trial of HTL0039732.
Limited ability to swallow or absorb oral medications.
Any other condition that, in the Investigator's opinion, would mean that the trial is not in the best interests of the potential participant.
Phase 1 Part B and Phase 2a:
Any live vaccines in the 4 weeks prior to enrolment.
Diagnosis of immunodeficiency.
Active autoimmune disease requiring systemic treatment in the 2 years prior to enrolment.
History or clinical suspicion of interstitial lung disease, history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
Hypersensitivity to atezolizumab or any of its excipients.
Prior adverse reaction to cancer immunotherapy that required steroid or other immunosuppressive treatment or led to discontinuation of that treatment.

Where it is running

Addenbrooke's Hospital — Cambridge, United Kingdom (enrolling)
Velindre Cancer Centre — Cardiff, United Kingdom (enrolling)
Clatterbridge Cancer Centre — Liverpool, United Kingdom (enrolling)
Guy's Hospital — London, United Kingdom (enrolling)
The Christie Hospital — Manchester, United Kingdom (enrolling)

Full record on ClinicalTrials.gov

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