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NeoplasmsPhase 1/2NCT05944237

HTL0039732 in Participants With Advanced Solid Tumours

A Phase 1/2 study testing HTL0039732 Capsules and HTL0039732 Capsules or HTL0039732 tablets and atezolizumab infusion in people with Neoplasms and Prostatic Neoplasms, Castration-Resistant, run by Cancer Research UK at 6 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
HTL0039732 Capsules and HTL0039732 Capsules or HTL0039732 tablets and atezolizumab infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
6 sitesUnited Kingdom
Study dates
2 Aug 2023to 31 Dec 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Consent to access and analysis of any available archival tissue or a fresh tumour sample at baseline, if archival tissue is unavailable.
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  • 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/genetic aberration, and/or other driver mutation/genetic aberration 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]); where applicable, results from validated immunohistochemistry are also acceptable.
  • Gastric or gastro-oesophageal 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).
  • For indications where anti-PD-1/PD-L1 therapy is standard of care (such as clear cell renal cell carcinoma, or gastric or GOJ adenocarcinoma with elevated PD-L1 expression), patients must have received that therapy and must be considered to have had progressive disease by the Investigator either on, or within 6 months after, that treatment.
  • Life expectancy of at least 12 weeks.
  • Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Haematological and biochemical indices within the protocol specified ranges.
  • Stable thyroid function tests. Stable doses of thyroxine replacement are permitted.
  • Aged 18 years or over at the time consent is given.

Who cannot join

  • 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.
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  • 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 or any of the excipients used in HTL0039732 Tablets (microcrystalline cellulose, mannitol, hydroxypropyl cellulose, croscarmellose sodium, magnesium stearate, silicon dioxide or Opadry® QX coating [macrogol (PEG) polyvinyl alcohol graft copolymer, talc, iron oxide red, part hydrolysed polyvinyl alcohol, iron oxide yellow, iron oxide black, titanium dioxide]).
  • Use of systemic immunosuppressive agent in the 2 weeks prior to enrolment. Exceptions apply.
  • Current or prior malignancy that could affect safety or efficacy assessment of the IMP or compliance with the protocol or interpretation of results. Patients with curatively-treated non-melanoma skin cancer, non-muscle-invasive bladder cancer, or carcinomas-in-situ are generally eligible.
  • 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.
  • Potential participants at increased risk of gastrointestinal bleeding (including individuals receiving concomitant anticoagulants, or with known coagulopathies or other factors predisposing them to bleeding) if intolerant to gastric protection therapy with PPIs or equivalent.
  • 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:
  • Clinically significant primary or secondary 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.

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Bristi Basu, Dr contact

+44 (0) 1223 769310

Bristi.Basu@nhs.net

6 sites in 1 country

United Kingdom6 sites, 6 recruiting

  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

    Bristi Basu, Dr, 01223 596105, Bristi.Basu@nhs.net

    Recruiting

  • Velindre Cancer Centre

    Cardiff, CF14 2TL

    Robert Jones, Dr, 02920 615888 Ext 6327, Robert.Hugh.Jones@wales.nhs.uk

    Recruiting

  • Ninewells Hospital

    Dundee, DD1 9SY

    Russell Petty Prof, +441382 383172, r.petty@dundee.ac.uk

    Recruiting

  • Clatterbridge Cancer Centre

    Liverpool, CH63 4JY

    Daniel Palmer, Prof, 0151 706 4172 / 0151 706 4177, palmerd@liverpool.ac.uk

    Recruiting

  • Guy's Hospital

    London, SE1 9RT

    Debashis Sarker, Dr, 020 7188 4249, Debashis.Sarker@kcl.ac.uk

    Recruiting

  • The Christie Hospital

    Manchester, M20 4BX

    Natalie Cook, Dr, 0161 918 7672, Natalie.Cook17@nhs.net

    Recruiting

Other trials in United Kingdom

About this study

Official title: 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

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.

Read the 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. Atezolizumab, 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.
Being tested
HTL0039732 Capsules, HTL0039732 Capsules or HTL0039732 tablets and atezolizumab infusion
Keywords
EP4 antagonist, Anti-PD-1/PD-L1 agents, PGE2, EP4, COX inhibitor
Medical subject headings
Neoplasms, Prostatic Neoplasms, Castration-Resistant, Stomach Neoplasms, Esophageal Neoplasms, Head and Neck Neoplasms, Colorectal Neoplasms, Pancreatic Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HTL0039732 CapsulesDrug

    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.

  • HTL0039732 Capsules or HTL0039732 tablets and atezolizumab infusionDrug

    HTL0039732 Capsules or HTL0039732 tablets 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 Day 1 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.

Study groups in NCT05944237
Study groupRoleWhat they receive
Phase 1 Part A HTL0039732 (Dose Escalation Monotherapy)ExperimentalGroups of participants will receive increasing doses of HTL0039732 Capsules as a single agent to find a safe dose and a dose that best targets cancer cells.
Receives: Drug: HTL0039732 Capsules
Phase 1 Part B HTL0039732 and Atezolizumab (Dose Escalation Combination)ExperimentalGroups of participants will receive increasing doses of HTL0039732 Capsules in combination with a fixed 1200 mg dose of atezolizumab to find a RP2D for HTL0039732.
Receives: Drug: HTL0039732 Capsules
Phase 2a HTL0039732 and Atezolizumab (Dose Expansion Combination)ExperimentalAn expansion cohort will receive the RP2D of HTL0039732 Capsules or HTL0039732 tablets in combination with a fixed 1200 mg dose of atezolizumab.
Receives: Drug: HTL0039732 Capsules or HTL0039732 tablets and atezolizumab infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD; Dose Escalation Phase)

    The MTD is the highest dose of HTL0039732 in the safe dose range, i.e. where there is a <25% probability of toxicity being above 30%.

    Measured: From first dose of HTL0039732 up to the end of Cycle 1, a time frame of up to 30 days.

  2. RP2D (Dose Escalation Phase)

    The RP2D for HTL0039732 will be determined after reviewing all of the clinically relevant toxicity, efficacy and pharmacokinetic (PK)/pharmacodynamic data by the Trial Management Group.

    Measured: From first dose of HTL0039732 up to the off-study visit (maximum 115 weeks).

  3. Number of Adverse Events (AEs) Related to HTL0039732 (Dose Escalation and Expansion Phase)

    Number of all grade AEs, and number of Grade 3, 4 and 5 AEs, considered at least possibly related to HTL0039732, graded according to National Cancer Institute Common Criteria for Adverse Events (NCI CTCAE) Version 5.0. Count of AEs by arm.

    Measured: Safety data will be collected from the time of informed consent until 28 days after the last dose of HTL0039732. The average time from consent to the end of follow-up will be presented.

  4. Number of AEs Related to Atezolizumab (Dose Escalation and Expansion Phase)

    Number of all grade AEs, and number of Grade 3, 4 and 5 AEs, considered at least possibly related to atezolizumab, graded according to NCI CTCAE Version 5.0. Count of AEs by arm.

    Measured: Safety data will be collected from the time of informed consent until 90 days after the last dose of atezolizumab. The average time from consent to the end of follow-up will be presented.

Secondary outcomes (18)

  1. Measurement of the PK Parameter Maximum (or Peak) Plasma Concentration (Cmax) of HTL0039732 (Dose Escalation and Expansion Phase)

    Plasma samples will be analysed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) to determine the Cmax of HTL0039732 after oral administration of HTL0039732 as monotherapy and in combination with atezolizumab, according to agreed standard operating procedures (SOPs) and validated methods. Not all participants may be analysed at all time points.

    Measured: From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).

  2. Measurement of the PK Parameter Time to Reach Maximum (or Peak) Plasma Concentration (Tmax) of HTL0039732 (Dose Escalation and Expansion Phase)

    Plasma samples will be analysed by LC-MS/MS to determine the Tmax of HTL0039732 after oral administration of HTL0039732 as monotherapy and in combination with atezolizumab, according to agreed SOPs and validated methods. Not all participants may be analysed at all time points.

    Measured: From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).

  3. Measurement of the PK Parameter Minimum Plasma Concentration (Cmin) of HTL0039732 (Dose Escalation and Expansion Phase)

    Plasma samples will be analysed by LC-MS/MS to determine the Cmin of HTL0039732 after oral administration of HTL0039732 as monotherapy and in combination with atezolizumab, according to agreed SOPs and validated methods. Not all participants may be analysed at all time points.

    Measured: From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).

  4. Measurement of the PK Parameter Area under the Plasma Concentration-Time Curve (AUC) (Dose Escalation and Expansion Phase)

    Plasma samples will be analysed by LC-MS/MS to determine the AUC of HTL0039732 after oral administration of HTL0039732 as monotherapy and in combination with atezolizumab, according to agreed SOPs and validated methods. Not all participants may be analysed at all time points.

    Measured: From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).

  5. Measurement of the PK Parameter Apparent Clearance (CL/F) (Dose Escalation and Expansion Phase)

    Plasma samples will be analysed by LC-MS/MS to determine the CL/F of HTL0039732 after oral administration of HTL0039732 as monotherapy and in combination with atezolizumab, according to agreed SOPs and validated methods. Not all participants may be analysed at all time points.

    Measured: From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).

  6. Measurement of the PK Parameter Apparent Volume of Distribution (V/F) (Dose Escalation and Expansion Phase)

    Plasma samples will be analysed by LC-MS/MS to determine the V/F of HTL0039732 after oral administration of HTL0039732 as monotherapy and in combination with atezolizumab, according to agreed SOPs and validated methods. Not all participants may be analysed at all time points.

    Measured: From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).

  7. Measurement of the PK Parameter Terminal Elimination Half-Life (T1/2) (Dose Escalation and Expansion Phase)

    Plasma samples will be analysed by LC-MS/MS to determine the T1/2 of HTL0039732 after oral administration of HTL0039732 as monotherapy and in combination with atezolizumab, according to agreed SOPs and validated methods. Not all participants may be analysed at all time points.

    Measured: From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).

  8. Determine the Magnitude and Duration of De-repression of Inhibition by Prostaglandin E2 of Lipopolysaccharide Induced Tumour Necrosis Alpha Production, Ex Vivo in Whole Blood (Dose Escalation and Expansion Phase).

    Mean percentage reversal at timepoints from baseline to final timepoint.

    Measured: From first dose of HTL0039732 until Cycle 2 Day 8 (max. 6 weeks).

  9. Best Anti-Tumour Response to HTL0039732 According to Response Evaluation Criteria in Solid Tumours (RECIST) version (v) 1.1 (Dose Escalation Phase Part A)

    Best radiological response, presented per arm by count of participants: complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), based on RECIST v1.1. A CR or PR should be confirmed by a subsequent assessment ≥4 weeks later. SD criteria must be met at least once ≥6 weeks after trial entry to be defined as SD.

    Measured: From baseline radiological disease assessment until End of Study visit (max. 118 weeks). Efficacy follow-up may continue until end of trial.

  10. Best Overall Response to HTL0039732 and Atezolizumab According to RECIST v 1.1 or Prostate Cancer Clinical Trials Working Group 3 (PCWG3) (Dose Escalation Phase Part B and Dose Expansion Phase)

    Best radiological response, presented per arm by count of participants: CR, PR, SD or PD, based on RECIST v1.1, or based on PCWG3 for participants with prostate cancer. A CR or PR should be confirmed by a subsequent assessment ≥4 weeks later. SD criteria must be met at least once ≥6 weeks after trial entry to be defined as SD.

    Measured: From baseline radiological disease assessment until End of Study visit (max. 118 weeks). Efficacy follow-up may continue until end of trial.

  11. Objective Response Rate According to RECIST 1.1 or by PCWG3 Criteria (Dose Escalation Phase Part B and Dose Expansion Phase)

    Percentage of participants, presented per arm, with CR or PR, based on RECIST v1.1, or based on PCWG3 for participants with prostate cancer. A CR or PR should be confirmed by a subsequent assessment ≥4 weeks later.

    Measured: From baseline radiological disease assessment until End of Study visit (max. 118 weeks). Efficacy follow-up may continue until end of trial.

  12. Duration of Response According to RECIST 1.1 or by PCWG3 Criteria (Dose Escalation Phase Part B and Dose Expansion Phase)

    The time in days from the date of first response (defined as CR or PR) to the date when PD is first identified, based on RECIST v1.1, or based on PCWG3 for participants with prostate cancer. A CR or PR should be confirmed by a subsequent assessment ≥4 weeks later.

    Measured: From time of first response until End of Study visit (max. 118 weeks). Efficacy follow-up may continue until end of trial.

  13. Disease Control Rate According to RECIST 1.1 or by PCWG3 Criteria (Dose Escalation Phase Part B and Dose Expansion Phase)

    Percentage of participants, presented per arm, with CR, PR or SD, based on RECIST v1.1, or based on PCWG3 for participants with prostate cancer. A CR or PR should be confirmed by a subsequent assessment ≥4 weeks later. SD criteria must be met at least once ≥6 weeks after trial entry to be defined as SD.

    Measured: From baseline radiological disease assessment until End of Study visit (max. 118 weeks). Efficacy follow-up may continue until end of trial.

  14. Progression Free Survival According to RECIST 1.1 or by PCWG3 Criteria (Dose Escalation Phase Part B and Dose Expansion Phase)

    The time in days from first dose of HTL0039732 until the time at which PD is identified, based on RECIST v1.1, or based on PCWG3 for participants with prostate cancer.

    Measured: From first dose of HTL0039732 until End of Study visit (max. 118 weeks). Efficacy follow-up may continue until end of trial.

  15. Prostate Specific Antigen (PSA) Response of at least 50% For Participants With Metastatic Castration Resistant Prostate Cancer (mCRPC) (Dose Escalation Phase Part B And Dose Expansion Phase)

    Percentage of participants with mCRPC showing a reduction from baseline in PSA response ≥50%.

    Measured: At least 12 weeks after baseline PSA.

  16. Change In Sum of Target Lesions According To RECIST 1.1 or By PCWG3 Criteria (Dose Escalation And Dose Expansion Phase).

    The change in the sum of diameters (SOD) for all target lesions calculated (by using the longest diameter for soft-tissue lesions and short axis for nodal lesions) will be reported.

    Measured: From baseline radiological disease assessment until End of Study visit (max. 118 weeks).

  17. Assess Tumour T Cell Infiltration In Baseline And On-Treatment Biopsies

    CD8 positive T-cells at baseline and on-treatment (biopsy).

    Measured: Baseline to Cycle 1 Day 15 (±7 days).

  18. Assess Change In Tumour T Cell Infiltration In Baseline and On-Treatment Biopsies

    Fold change in CD8 positive T-cells between baseline and on-treatment biopsy.

    Measured: Baseline to Cycle 1 Day 15 (±7 days).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2023
  2. Study start2 Aug 2023
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05944237
Sponsor's protocol ID
CRUKD/22/001
Other IDs
IRAS ID: 1006164
Status last verified
Sep 2026
First submitted
26 Jun 2023
Last updated
1 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Astley D, Svetlik S, Barnett S, Veal GJ. Development and validation of a LC-MS/MS method for the quantification of the E-type prostanoid receptor 4 antagonist HTL0039732 in human plasma, for a Phase I/IIa clinical trial. Bioanalysis. 2026 Aug 6:1-10. doi: 10.1080/17576180.2026.2712785. Online ahead of print.

    PubMed 42558019

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing HTL0039732 Capsules and HTL0039732 Capsules or HTL0039732 tablets and atezolizumab infusion in people with Neoplasms and Prostatic Neoplasms, Castration-Resistant, run by Cancer Research UK at 6 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Bristi Basu, Dr (+44 (0) 1223 769310, Bristi.Basu@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD; Dose Escalation Phase) (time frame: From first dose of HTL0039732 up to the end of Cycle 1, a time frame of up to 30 days.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05944237, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.

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