EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial - 1)

Inclusion Criteria:

1. Provision of written informed consent.

2. Male or female, ≥ 18 years of age.

3. An ECOG performance status of 0 or 1.

4. Willing to permit access to stored historical tumour tissue and prior tumourradiological assessments and tumour biomarker data (if available).

5. Able to take oral medications and be willing to record daily adherence to the studydrug.

6. Female participants must be of non-child-bearing potential, or, if of childbearingpotential must have a negative pregnancy test (as required by protocol), must use ahighly effective method of contraception combined with a condom and not donate ova (for the protocol specified period of time).

7. Male participants must use a condom and their female participant must also use ahighly effective method of contraception (for the protocol specified period oftime), if engaging in sexual intercourse with a female partner who could becomepregnant and not donate sperm.

8. Estimated life expectancy of at least 3 months, in the opinion of the PI.

9. Willing and able to comply with all scheduled visits, treatment plans, laboratorytests, and other study procedures. Module 1 (Parts A, B and C) and Module 2 (Parts A and B)

10. Participant has cytologically or histologically confirmed locally advanced ormetastatic solid malignancy for which no further standard of care (SoC) therapy isavailable (or no SoC therapy exists), or who have been offered and declined SoCtherapy, or are intolerant of SoC therapy. Module 1 (Parts A, B and C) and Module 2 (Parts A and B) only

11. Participant has measurable disease per RECIST 1.1/iRECIST. Module 1 (Part B) and Module 2 (Part B) Only

12. Participant has at least one tumour lesion amenable to serial biopsies and iswilling to provide consent for biopsies and has measurable disease per RECIST 1.1/iRECIST, excluding the lesion(s) identified for biopsy. Module 2 (Part C) Cohort 1

13. Participants with histologically confirmed persistent, recurrent or metastaticcervical cancer who are not amenable to curative therapy.

14. Participants should have received at least 3 months first line anti-PD(L)-1maintenance therapy (± bevacizumab) following combination with chemotherapy +anti-PD-(L)1 ± bevacizumab and this should have included at least a 10-week periodwithout progression.

15. Participants may enrol in the study immediately following progression on the firstline CPI or may have received 1 further line of systemic cancer therapy afterprogression on CPI. Cohort 2

16. Participants with histologically confirmed hepatocellular carcinoma who are notamenable to curative therapy and ineligible for loco-regional therapy.

17. Participants should have received at least 3 months first line anti-PD(L)-1containing therapy and this should have included at least a 10-week period withoutprogression per Investigator assessment.

18. Participants may enrol in the study immediately following progression on the firstline CPI or may have received 1 further line of systemic cancer therapy afterprogression on CPI.

19. Participant has Child-Pugh score class A liver function. Cohort 3

20. Participants with cytologically or histologically confirmed advanced, recurrent ormetastatic disease, which is not amenable to curative therapy, in up to 5 types ofsolid tumour with moderate to high median TMB (NSCLC, urothelial, SCCHN,gastric/gastro-oesophageal adenocarcinoma, oesophageal SCC).

21. Participants should have received at least ≥ 3 months first line anti-PD(L)-1 eitherinitiated as monotherapy or following completion of chemotherapy + anti PD-(L)1.

22. Participants may enrol in the study immediately following progression on the firstline CPI or may have received 1 further line of systemic cancer therapy afterprogression on CPI.

Exclusion Criteria:

1. Prior therapy with an ERAP1 inhibitor.

2. Any other malignancy within the past 3 years, with the exception of cervicalintraepithelial neoplasia and nonmelanoma skin cancer.

3. Any unresolved toxicity (except alopecia) from prior therapy of ≥ CTCAE Grade 1.Participants with Grade 2 toxicity that is not clinically significant (e.g.,alopecia, vitiligo), or that is deemed stable or irreversible (e.g., peripheralneuropathy) can be enrolled. time), if engaging in sexual intercourse with a female partner who could become
pregnant and not donate sperm.
 

4. Estimated life expectancy of at least 3 months, in the opinion of the PI.
 

5. Willing and able to comply with all scheduled visits, treatment plans, laboratory
tests, and other study procedures.
 
Module 1 (Parts A, B and C) and Module 2 (Parts A and B)
 

6. Participant has cytologically or histologically confirmed locally advanced or
metastatic solid malignancy for which no further standard of care (SoC) therapy is
available (or no SoC therapy exists), or who have been offered and declined SoC
therapy, or are intolerant of SoC therapy.
 
Module 1 (Parts A, B and C) and Module 2 (Parts A and B) only
 

7. Participant has measurable disease per RECIST 1.1/iRECIST.
 
Module 1 (Part B) and Module 2 (Part B) Only
 

8. Participant has at least one tumour lesion amenable to serial biopsies and is
willing to provide consent for biopsies and has measurable disease per RECIST
 1.1/iRECIST, excluding the lesion(s) identified for biopsy.
 
Module 2 (Part C) Cohort 1
 

9. Participants with histologically confirmed persistent, recurrent or metastatic
cervical cancer who are not amenable to curative therapy.
 

10. Participants should have received at least 3 months first line anti-PD(L)-1
maintenance therapy (± bevacizumab) following combination with chemotherapy +
anti-PD-(L)1 ± bevacizumab and this should have included at least a 10-week period
without progression.
 

11. Participants may enrol in the study immediately following progression on the first
line CPI or may have received 1 further line of systemic cancer therapy after
progression on CPI.
 
Cohort 2
 

12. Participants with histologically confirmed hepatocellular carcinoma who are not
amenable to curative therapy and ineligible for loco-regional therapy.
 

13. Participants should have received at least 3 months first line anti-PD(L)-1
containing therapy and this should have included at least a 10-week period without
progression per Investigator assessment.
 

14. Participants may enrol in the study immediately following progression on the first
line CPI or may have received 1 further line of systemic cancer therapy after
progression on CPI.
 

15. Participant has Child-Pugh score class A liver function.
 
Cohort 3
 

16. Participants with cytologically or histologically confirmed advanced, recurrent or
metastatic disease, which is not amenable to curative therapy, in up to 5 types of
solid tumour with moderate to high median TMB (NSCLC, urothelial, SCCHN,
gastric/gastro-oesophageal adenocarcinoma, oesophageal SCC).
 

17. Participants should have received at least ≥ 3 months first line anti-PD(L)-1 either
initiated as monotherapy or following completion of chemotherapy + anti PD-(L)1.
 

18. Participants may enrol in the study immediately following progression on the first
line CPI or may have received 1 further line of systemic cancer therapy after
progression on CPI.
 
 Exclusion Criteria:
 

19. Prior therapy with an ERAP1 inhibitor.
 

20. Any other malignancy within the past 3 years, with the exception of cervical
intraepithelial neoplasia and nonmelanoma skin cancer.
 

21. Any unresolved toxicity (except alopecia) from prior therapy of ≥ CTCAE Grade 1.
Participants with Grade 2 toxicity that is not clinically significant (e.g.,
alopecia, vitiligo), or that is deemed stable or irreversible (e.g., peripheral
neuropathy) can be enrolled.
 

22. Active or documented history of autoimmune disease (within 2 years) requiringsystemic immunosuppressive therapy, or participant is immunocompromised for anyother reason (as determined by the Investigator).

23. Spinal cord compression or brain metastases, unless asymptomatic, stable, and notrequiring steroids for at least 4 weeks (if stable and requiring no intervention,the participant can be enrolled in the study).

24. Uncontrolled seizures.

25. Active infection requiring therapy within 14 days prior to the day of first dose ofIMP.

26. Severe or uncontrolled medical condition (e.g., severe chronic obstructive pulmonarydisease, severe Parkinson's disease, active inflammatory bowel disease) orpsychiatric condition.

27. Active bleeding diatheses.

28. Participant has received an organ transplant.

29. Known active hepatitis B, hepatitis C, or human immunodeficiency virus infection (HIV).

30. Participant is breastfeeding or pregnant.

31. Receipt of licenced or unlicenced cytotoxic, noncytotoxic or small moleculetreatment for the malignancy within 28 days or 5 half-lives, whichever is shorterprior to the day of first dose of IMP.

32. Receipt of oral corticosteroids (at a dose > 10 mg prednisone/day or equivalent)within 14 days (except for subjects receiving corticosteroids for adrenalinsufficiency).

33. Receipt of St John's Wort or of another concomitant medication, herbal supplement,or food that is a strong inhibitor or inducer of CYP3A4 enzymes within 14 days.

34. Receipt of a blood transfusion (blood or blood products) within 7 days.

35. Impaired hepatic or renal function.

36. Liver function deteriorating in a manner that would likely make the participantineligible per protocol specified requirements.

37. Other evidence of impaired hepatic synthesis function.

38. Inadequate bone marrow reserve or organ function.

39. Any prior history of persistent (> 4 weeks) severe pancytopenia due to previoustherapy rather than to disease (ANC < 0.5 × 10^9/L or platelets < 50 x 10^9/L).

40. Cardiac dysfunction or other clinically significant cardiac pathology likely toimpair the participants ability to participate in the study.

41. Mean QTcF > 450 ms for males or > 470 ms for females.

42. Any clinically important abnormalities in rhythm, conduction, or morphology onresting ECG. Controlled atrial fibrillation is permitted.

43. Any factor that in the Investigator's opinion increases the risk of QTc prolongationor arrythmic events.

44. In the opinion of the Investigator, unlikely to comply with study procedures,restrictions, or requirements.

45. A history of haemolytic anaemia or marrow aplasia.

46. Has received a live-virus vaccination within 28 days. Note: seasonal flu or COVIDvaccines that do not contain live virus are permitted.

47. History of Grade 3 or 4 pneumonitis or interstitial lung disease within the last 5years, or other clinically significant pulmonary pathology likely to impair abilityto participate in the study. Module 2 all Parts and Module 1A Crossover Participants Only Only

48. Has discontinued a prior checkpoint inhibitor due to toxicity.

49. Hypersensitivity to cemiplimab or any of its excipients, or contraindicated tocemiplimab per approved local labelling.

50. Has experienced ≥ Grade 2 immune-mediated AE on this study (applies to crossoverparticipants only).