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
2 other identifiers
interventional
150
1 country
5
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2023
Longer than P75 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 26, 2023
CompletedFirst Posted
Study publicly available on registry
July 13, 2023
CompletedStudy Start
First participant enrolled
July 13, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
June 8, 2025
June 1, 2025
3.9 years
June 26, 2023
June 5, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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%.
From first dose of HTL0039732 up to the end of Cycle 1, a time frame of up to 30 days.
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.
From first dose of HTL0039732 up to the off-study visit (maximum 115 weeks).
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.
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.
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.
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)
Measurement of the PK Parameter Maximum (or Peak) Plasma Concentration (Cmax) of HTL0039732 (Dose Escalation and Expansion Phase)
From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).
Measurement of the PK Parameter Time to Reach Maximum (or Peak) Plasma Concentration (Tmax) of HTL0039732 (Dose Escalation and Expansion Phase)
Timeframe: From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).
Measurement of the PK Parameter Minimum Plasma Concentration (Cmin) of HTL0039732 (Dose Escalation and Expansion Phase)
From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).
Measurement of the PK Parameter Area under the Plasma Concentration-Time Curve (AUC) (Dose Escalation and Expansion Phase)
From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).
Measurement of the PK Parameter Apparent Clearance (CL/F) (Dose Escalation and Expansion Phase)
From first dose of HTL0039732 until Cycle 6 Day 1 (max. 20 weeks).
- +13 more secondary outcomes
Study Arms (3)
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.
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.
Phase 2a HTL0039732 and Atezolizumab (Dose Expansion Combination)
EXPERIMENTALAn expansion cohort will receive the RP2D of HTL0039732 Capsules in combination with a fixed 1200 mg dose of atezolizumab.
Interventions
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 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.
Eligibility Criteria
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;
- +15 more criteria
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.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cancer Research UKlead
- Nxera Pharma UK Limitedcollaborator
Study Sites (5)
Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
Clatterbridge Cancer Centre
Liverpool, CH63 4JY, United Kingdom
Guy's Hospital
London, SE1 9RT, United Kingdom
The Christie Hospital
Manchester, M20 4BX, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 26, 2023
First Posted
July 13, 2023
Study Start
July 13, 2023
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
June 1, 2027
Last Updated
June 8, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will not share