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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Bristi
Basu
bristi.basu@nhs.net
Laura
Brotherton
laura.brotherton@cancer.org.uk
Bristi
Basu
bristi.basu@nhs.net
Hayley
Cartwright
hayley.cartwright@cancer.org.uk
Malignant neoplasms of digestive organsMalignant neoplasms of female genital organsMalignant neoplasms of lip, oral cavity and pharynxMalignant neoplasms of mesothelial and soft tissueMalignant neoplasms of respiratory and intrathoracic organsMalignant neoplasms of urinary tract
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
This CRUKD/22/001 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),in participants with advanced cancers.
HTL0039732 is expected to work in two ways: (i) by slowing the cancer growth and; (ii) by increasing immune system activity that will then destroy the cancer cells.
This is a first in human (FIH) trial with multiple expansion cohorts intended to identify a safe dose of HTL0039732 as a monotherapy and in combination with atezolizumab,as well as to provide preliminary assessment of pharmacodynamic effects of HTL0039732 on the immune response to cancer and preliminary evidence of clinical efficacy in cancers believed to be Prostaglandin (PG) E2/EP4 dependent.
HTL0039732 is a capsule given orally. HTL0039732 will be assessed as a monotherapy and in combination with atezolizumab and potentially other anti-cancer agents. There will be a monotherapy arm and a combination arm (with atezolizumab) in the dose escalation phase.
The main aims of the trial are:
• To establish the RP2D of HTL0039732 as a monotherapy and in combination with atezolizumab
• To assess the safety and tolerability profile of HTL0039732 as a monotherapy and in combination with atezolizumab
• To investigate the PK profile of HTL0039732 as a monotherapy and in combination with atezolizumab
• To explore the anti-tumour activity
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
Interventional type: Drug;
You can take part if:
You may not be able to take part if:
1. Radiotherapy (except for palliative reasons) or chemotherapy during the previous 4 weeks prior to enrolment (6 weeks for nitrosoureas,mitomycin-C); non-chemotherapy systemic anti-cancer therapy (apart from life-long hormone suppression such as luteinising hormone-releasing hormone [LHRH] agents in participants with mCRPC) or IMPs during the previous 4 weeks prior to enrolment (or 5 half-lives,whichever is shorter); or first dose of an immunotherapy during the previous 12 weeks,before first dose of HTL0039732. 2. Potential participants with ongoing toxic manifestations of previous treatments that are more severe than CTCAE Version 5.0 Grade 1. Exceptions to this are alopecia and any ongoing toxic manifestation that,in the opinion of the Investigator and discussed with Sponsor,would not be expected to risk compromising the health of the potential participant or the interpretation of trial data. 3. Any CNS metastases (unless potential participants have had local therapy and are asymptomatic,radiologically stable and have been off steroids for at least 4 weeks prior to enrolment). 4. Women of childbearing potential8 (or who are already pregnant or lactating). However,those who meet the following points are considered eligible if they: • Have a negative serum or urine pregnancy test before enrolment and either: o Agree to use one form of highly effective contraception such as: i. oral,intravaginal or transdermal combined (oestrogen and progestogen containing) hormonal contraception; ii. oral,injectable or implantable9 progestogen-only hormonal contraception associated with inhibition of ovulation; iii. intrauterine device9; iv. intrauterine hormone-releasing system9; v. bilateral tubal occlusion9; vi. vasectomised partner 9,10; Plus a barrier method (e.g.,condom plus spermicide); o Or agree to sexual abstinence.11 Effective from the first administration of HTL0039732,throughout the trial and for 6 months after the last administration of HTL0039732 or 5 months after the last administration of atezolizumab,whichever is later. 5. Males with partners of childbearing potential8. However,those who meet the following points are considered eligible: • Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or sexual abstinence11,effective from the first administration of HTL0039732,throughout the trial and for 6 months after the last administration of HTL0039732 or 5 months after the last administration of atezolizumab,whichever is later; • Males with pregnant or lactating partners must be advised to use barrier method contraception (e.g.,condom plus spermicide) to prevent exposure of the foetus or neonate,effective from the first administration of HTL0039732,throughout the trial and for 6 months after the last administration of HTL0039732 or 5 months after the last administration of atezolizumab,whichever is later; • Non-vasectomised males must also be willing to ensure that any partner of childbearing potential uses a highly effective method of contraception (as per exclusion criteria 4 above) or agree to sexual abstinence11 for the same duration. 6. Major thoracic or abdominal surgery from which the potential participant has not yet recovered. 7. At high medical risk because of non-malignant systemic disease,including active uncontrolled infection. 8. Known history of current or latent tuberculosis,HIV or Hepatitis B or C infection. 9. Prior treatment with EP4 inhibitor. 10. Treatment with selective COX-2 inhibitor in the 8 weeks prior to enrolment. 11. Known hypersensitivity or intolerance to HPMC. 12. Use of systemic immunosuppressive agent in the 2 weeks prior to enrolment. Immunosuppressive agents include steroids such as prednisolone (doses =15 mg daily) or dexamethasone (doses =2 mg daily).12 Topical or inhaled steroids for pre-existing diseases are allowed. 13. Potential participants with significant cardiovascular disease are excluded as defined by: a. Current congestive heart failure requiring therapy (New York Heart Association III or IV – APPENDIX 3) or known left ventricular ejection fraction (LVEF) <40% (moderate or severe); b. History of unstable angina pectoris or myocardial infarction within 6 months prior to trial entry,or current poorly controlled angina (symptoms weekly or more); c. Presence of symptomatic or severe valvular heart disease (severe by local echocardiographic criteria or American Heart Association/American College of Cardiology [AHA/ACC] Stage C or D – APPENDIX 4); d. History of a clinically significant cardiac arrhythmia within 6 months prior to trial entry (asymptomatic atrial fibrillation or asymptomatic first-degree heart block are permitted). 14. Known active peptic ulcer disease,or symptoms of gastritis,dyspepsia or gastro-oesophageal reflux disease (one or more episodes per week). Asymptomatic gastritis / dyspepsia / gastro-oesophageal reflux disease on PPIs,H2 antagonist or antacid therapy is permitted. 15. Current or planned participation in another interventional clinical trial,whilst taking part in this Phase I/IIa trial of HTL0039732. Participation in an observational trial or interventional clinical trial that does not involve administration of an IMP and that would not place an unacceptable burden on the potential participant,in the opinion of the Investigator,would be acceptable. 16. Limited ability to swallow or absorb oral medications. 17. 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 I Part B and Phase IIa - HTL0039732 in combination with atezolizumab: 18. Any live vaccines in the 4 weeks prior to enrolment. 19. Diagnosis of immunodeficiency. 20. Active autoimmune disease that has required systemic treatment in the 2 years prior to enrolment (i.e.,with use of disease modifying agents,corticosteroids or immunosuppressive drugs) 12. 21. History or clinical suspicion of interstitial lung disease,a history of (non-infectious) pneumonitis that required steroids,or current pneumonitis. 22. Hypersensitivity to atezolizumab or any of its excipients (including L-histidine,glacial acetic acid,sucrose or polysorbate 20).
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Bristi
Basu
bristi.basu@nhs.net
Bristi
Basu
bristi.basu@nhs.net
Laura
Brotherton
laura.brotherton@cancer.org.uk
Hayley
Cartwright
hayley.cartwright@cancer.org.uk
The study is sponsored by CANCER RESEARCH UK and funded by CANCER RESEARCH UK .
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Read full details
for Trial ID: CPMS 54381
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