• 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).

⁃ 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.