TT-702 in Patients With Advanced Solid Tumours.

Inclusion criteria: 1. Be able to provide informed consent and be capable of co-operating with IMP administration, procedures and follow-up. 2. Be willing to provide samples (blood and tissue) as required. 3. Consent to access any available archival tissue. 4. Consent for fresh tumour biopsy samples at baseline and on trial (may be Investigator mandated for patients in the dose escalation phase. Investigators will consider whether a biopsy is feasible for the patient in the dose escalation phase and this will not impede participation in the trial if biopsy is not a suitable option. 5. Life expectancy estimated by the Investigator to be at least 12 weeks. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 7. Aged 16 years or over at the time consent is given. 8. Haematological and biochemical indices within the protocol specified ranges. 9. Objectively or measurable evaluable disease, radiologically according to RECIST Version 1.1 (and/or, in mCRPC patients, according to PCWG3 criteria). Has radiological disease progression (and/or, in mCRPC patients, PSA progression according to PCWG3 criteria) at the time of trial enrolment. 10. Castrate levels of testosterone (\<1.7 nmol/L \[50 ng/dL\]) (mCRPC patients only). 11. Phase I, dose escalation phase Histologically or cytologically proven advanced solid tumours refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the patient. Phase I dose escalation cohorts are: * Phase I, Cohort 1M (TT-702 monotherapy cohort): MMRd tumour, confirmed by either: i. Loss of MSH2, MSH6, MLH1, PMS2 by ICH (total or near total) OR ii. Loss of function mutation f MMR gene(s) AND iii. High tumour mutation burden (depends on assay but typically \>15 mutations/MB sequenced). Non-MMRd tumours: mCRPC: - Prior treatment with a next generation hormonal agent. - Adenocarcinoma without neuroendocrine or small cell features. TNBC: \- Human epidermal growth factor receptor 2 negativity (negative immunohistochemistry \[IHC\] staining \[score 0 or 1\] or negative fluorescence in situ hybridisation based on the American Society of Clinical Oncology/College of American Pathologists guidelines and recommendations) and determined through local testing in NHS lab within UKAS/ISO 15198 scope of accreditation. * ER and progesterone receptor negativity (\<1% positive staining cells in the invasive tumour) determined locally using IHC per American Society of Clinical Oncology/College of American Pathologists criteria. * Patients who have received prior anti-PD-1/anti-PD-L1 agent must have experienced Investigator-assessed initial clinical benefit from the most recent anti-PD-1/anti-PD-L1 treatment (either as monotherapy or in combination with other compounds) for at least 10 weeks, followed by subsequent progression. Initial benefit is defined as SD or better with an anti-PD-1/anti-PD-L1 therapy. CRC, NSCLC and PDAC: \- Histologically or cytologically proven diagnosis of CRC, NSCLC or PDAC • Phase I, Cohort 1P (TT-702 \& PD-1/PD-L1 combination cohort): Patients who have had prior treatment with an ICI. Phase II (expansion phase) Histologically or cytologically proven advanced solid tumour of particular interest based on preclinical and clinical data, refractory to conventional treatment or, for which no conventional therapy is considered appropriate by the Investigator or, is declined by the patient. Phase II expansion cohorts are: Cohort 2M (TT-702 Monotherapy expansion cohort) and Cohort 2P (TT-702 \& anti-PD-1/PD-L1 combination cohort): * Patients must have been previously treated with an ICI * MMRd tumour, confirmed by either: i. Loss of MSH2, MSH6, MLH1, PMS2 by IHC (total or near total) OR ii. Loss of function mutation of MMR gene(s) AND iii. High tumour mutation burden (depends on assay but typically \>15 mutations/MB sequenced). Exclusion criteria: <!-- --> 1. Radiotherapy (except single fractions for palliative reasons), endocrine therapy during the previous four weeks, immunotherapy and chemotherapy during the previous four weeks(previous six weeks for nitrosoureas, Mitomycin-C) before receiving TT-702. A washout period of eight weeks is required for enzalutamide and apalutamide before the patient receives their first dose of TT-702. A washout period of 4 weeks or 5 half-lives whichever is shorter for any other previous preceding IMPs is required before the patient receives their first dose of TT-702 (no washout is needed from ICI). 2. Patients with ongoing toxic manifestations of previous treatments greater than NCI CTCAE Version 5.0 Grade 1. Exceptions to this are alopecia and any ongoing toxic manifestation which in the opinion of the Investigator should not exclude the patient. 3. Patients with symptomatic brain or leptomeningeal metastases should be excluded. Asymptomatic patients with previously treated and stable brain metastases (in previous four weeks to trial entry) and not requiring any steroids are eligible for the trial. Patients who are stable on anticonvulsants are also eligible. 4. Women of childbearing potential (or are already pregnant or lactating). However, those patients who meet the following points are considered eligible: • Have a negative highly sensitive pregnancy test of a serum sample within 7 days prior to trial inclusion; and • Agree to use two forms of medically approved contraception: i. one highly effective form including but not limited to: oral, injected,implanted, transdermal or intravaginal hormonal contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormonereleasing system, bilateral tubal occlusion or vasectomised partner; ii. plus a barrier method (for example, condom plus spermicide); iii. or agree to sexual abstinence. Effective from the first administration of TT-702, throughout the tria