Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease

Inclusion Criteria:

1. Signed written informed consent

2. Histologic confirmation of malignancies under treatment with single agentanti-PD1/PDL1 immunotherapy per clinical practice (see cohort specific inclusioncriteria) with immune checkpoint inhibitors approved by Italian national drugregulatory agencies (Agenzia Italiana del Farmaco, AIFA)

3. Having a disease stability as assessed by AIFA monitoring sheet

4. Presence of at least 2 measurable target lesions, of which at least one to befollowed up as per RECIST and one suitable for CIRT

5. Willing and able to comply with scheduled visits, treatment schedule, laboratorytesting, and other requirements of the study

6. Females and males, 18 years of age or older (no upper limit for age)

7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

8. Subjects must have measurable disease by CT or MRI per RECIST 1.1

Exclusion Criteria:

1. Patients treated with chemo-immunotherapy associations

2. Patients treated with immunotherapy combinations (e.g. subjects treated withanti-CTLA4 + anti-PD1/PDL1 are excluded)

3. Patients receiving immunotherapy within clinical trials

4. Patients receiving off-label immunotherapy or within expanded access programs or ascompassionate use

5. Patients with high tumor burden defined as > 10 lesions and/or sum of diameters > 19cm

6. Patients with distant metastases only located in the CNS are excluded

7. Any serious or uncontrolled medical disorder that, in the opinion of theinvestigator, may increase the risk associated with study participation or studydrug administration, impair the ability of the subject to receive protocol therapy,or interfere with the interpretation of study results

8. Patients with autoimmune diseases (ADs), including local and systemiccollagen-vascular (CVD) and inflammatory bowel diseases (IBD)

9. Previous RT, regardless of energy, on the metastatic site selected to be irradiated.

10. Any immune-related CTCAE grade 4 adverse event, before study entry

11. Any CTCAE grade ≥3 immune-related adverse event observed within 3 weeks prior toCIRT start

12. Presence of metal prostheses or any other condition to prevent adequate imaging foridentification of the target volume and calculation of the dose

13. Loco-regional conditions not allowing hadron therapy (e.g. active infections in RTtarget region)

14. Prisoners or subjects who are involuntarily incarcerated

15. Subjects who are compulsorily detained for treatment of either a psychiatric orphysical illness (e.g. infectious disease)