This study aims to find the appropriate dose for an oral drug (PTT-4256) in people with solid cancers that are locally advanced or metastatic.A Modular, Open Label, Dose Finding, Phase 1/2 Clinical Trial in Patients With Solid Tumours to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of PTT-4256.

Exclusion

Exclusion Criteria:

1. Inability or unwillingness to adhere to the study protocol, including study procedures and oral intake of the IP.

2. Active primary central nervous system (CNS) malignancy, active CNS metastases or leptomeningeal disease. Participants with previously treated primary CNS malignancy or CNS metastases are eligible to participate if:

   1. they have stable and controlled neurological symptoms without deterioration;
   2. they have stable disease as assessed by imaging (preferably contrast-enhanced MRI) for at least 28 days prior to first IMP administration;
   3. they have no evidence of new or enlarging brain metastases; and
   4. they are not using corticosteroids for at least 7 days prior to first IMP administration.
3. Unresolved or unstable serious toxic side effects of prior chemotherapy or radiotherapy, ie, ≥ Grade 2 per CTCAE v5.0 except fatigue, alopecia, infertility, or those relating to palliative radiotherapy within 6 weeks prior to first IMP administration. Participants with residual AEs > Grade 1 considered not clinically significant may be considered eligible on a case-by-case basis, in discussion with the Sponsor.

4. Concurrent active or previous history of other malignancy within the past 2 years before first IMP administration except:

   1. Malignancy (other than in situ) treated with curative intent and with no known active disease present for ≥ 2 years before first IMP administration and felt to be at low risk of recurrence by the Investigator;
   2. Adequately treated non-melanoma skin cancer or lentigo malignant with no evidence of disease;
   3. Adequately treated in situ cancer without evidence of disease.
5. Received anti-cancer therapy (including chemotherapy, immunotherapy, radiation therapy, biologic therapy, or any investigational therapy) within 28 days or 5 half-lives of the therapeutic agent, whichever is shorter, prior to the first IMP administration. Palliative adiotherapy given within 28 days prior to the first IMP administration may be considered eligible on a case-by-case basis, in discussion with the Sponsor.
6. Uncontrolled symptomatic malignant effusion(s) or those requiring recurrent drainage in the opinion of the Investigator.
7. Participants with clinically significant active autoimmune or chronic inflammatory disease that is not well controlled with standard therapy in the opinion of the Investigator.
8. Grade 3 or higher immunotherapy-induced autoimmune hepatitis.

9. Participants with:

   1. symptomatic colitis of any CTCAE v5.0 Grade and aetiology within 4 weeks before first dosing,
   2. a history of autoimmune (including but not restricted to Crohn's disease, ulcerative colitis, and celiac's disease) or idiopathic (including but not restricted to pseudomembranous, ischaemic and microscopic) colitis, and/or,
   3. a history of drug-induced colitis of CTCAE v5.0 Grade 3 or higher.
10. History of primary immunodeficiency, bone marrow transplantation or solid organ transplantation.
11. Use of systemic immunosuppressive medication (including > 10 mg prednisolone per day or equivalent) within 14 days prior to the first IMP administration. Note that use of immunosuppressive medications as prophylaxis in participants with contrast allergies is acceptable. Adrenal replacement corticosteroid doses ≤10 mg daily prednisone equivalent are permitted, as are topical, inhaled, intra-articular or intra-nasal corticosteroids.
12. Participants with active Hepatitis B virus (HBV) hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at Screening) or Hepatitis C virus (HCV) hepatitis. Participants with resolved past HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
13. Participants with active HIV infection or known history of HIV infection.
14. Active infection requiring systemic antibacterial, antiviral or anti-fungal therapy for ≤ 7 days of first IMP administration. Note that participants on antibacterial, anti-fungal or antiviral prophylaxis are eligible.
15. Uncontrolled or recent history of clinically significant cardiovascular disease: Symptomatic heart failure (New York Heart Association classes II-IV), unstable angina, myocardial infarction, serious/uncontrolled/unstable cardiac arrhythmia, cerebral vascular accident, coronary/peripheral artery bypass graft surgery, transient ischaemic attack, or pulmonary embolism within 4 months prior to first IMP administration. Note that participants with small pulmonary emboli not thought to put them at higher risk may be considered eligible on a case-by-case basis, in discussion with the Sponsor.
16. Confirmed Baseline QTcF > 450 msec for males and > 470 msec for females (triplicate ECG) or history of torsades de pointes or history of congenital long QT syndrome. Note that participants with an apparent prolonged QT due to bundle branch block may be considered eligible on a case-by-case basis, in discussion with the MM.
17. History of clinically significant interstitial lung disease, or active non-infectious pneumonitis, or which may interfere with the detection or management of suspected drug related pulmonary toxicity.
18. Has had or is scheduled to have major surgery < 28 days prior to the first IMP administration. Elective surgical procedures not considered to put participants at higher risk of AEs may be allowed on a case-by-case basis, in discussion with the Sponsor.
19. Any other concurrent severe and/or uncontrolled medical, surgical or psychiatric and/or social condition which, in the view of the Investigator, could compromise the participant's safety or ability to participate in the study and make them unsuitable for participation.
20. Use of other investigational medicinal products within 2 weeks or at least 5 half-lives (whichever is longer) before IMP administration.
21. Must not have had a live vaccine administration ≤ 28 days prior to the first dose of the IMP.
22. Participants with known active or suspected alcohol or drug abuse that may interfere with the study in the opinion of the Investigator.
23. Gastrointestinal conditions that may affect oral absorption of drugs in the opinion of the Investigator, including but not restricted to gastroparesis and short bowel syndrome.