• histologically confirmed pancreatic cancer, virus-associated tumors \[including papillomaviruses-related cancers (cervical, head and neck, and nasal), Epstein-Barr virus (nasopharyngeal carcinoma) and Kaposi's sarcoma-associated herpes virus), non-small cell lung cancer, soft-tissue sarcomas, bladder cancer, triple negative breast cancer. For population 4, diagnosis must be confirmed by the RRePS Network as recommended by the French NCI. For population 2, papillomavirus-related cancers must be eligible whatever the genotype but in case of viral genotype is not available, IHC p16 positive must be provided, hepatocellular carcinoma must be confirmed by Hepatite B or C infection, HHV-8 and Epstein-Barr virus related cancers must be confirmed by molecular analysis,

• Metastatic disease,

• Age ≥ 18 years,

• ECOG ≤ 1,

• At least two lesions: one extra cerebral lesion that can be treated by radiotherapy and one site of disease that must be uni-dimensionally ≥ 10 mm considered as measurable according to RECIST v1.1. This lesion will not be treated by radiotherapy, however, note that lesion(s) that will be treated by radiotherapy will also be considered as measurable. Note that the largest size of the metastases to be irradiated will be 3cm and at that previous irradiation of these lesions is not allowed,

• Life expectancy \> 6 months,

• At least one tumor site that can be biopsied for research purpose. Tumor lesion in close proximity to vascular structures such as large vessels, aneurysm or pulmonary arteriovenous malformation will not be considered for biopsy,

• Availability of archived paraffin-embedded tumor tissue for research purpose,

• Participant must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement,

⁃ Participants who received prior anti-PD-1/L1 therapy must fulfill the following requirements - population 3 and population 5 only

∙ Have achieved a complete response, partial response or stable disease and subsequently had disease progression while still on anti-PD-1/L1 therapy

‣ Have received at least two doses of an approved anti-PD-1/L1 therapy (by any regulatory authority)

‣ Have demonstrated disease progression as defined by RECIST v1.1 within 18 weeks from the last dose of the anti- PD-1/L1 therapy.

⁃ Adequate hematological, renal, metabolic and hepatic functions

⁃ No prior or concurrent malignant disease needing an active treatment,

⁃ At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,

⁃ Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment, excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2,

⁃ Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to inclusion.

⁃ Both women and men must agree to use an effective method of contraception throughout the treatment period and for five months after discontinuation of treatment.

⁃ Voluntary signed and dated written informed consents prior to any specific study procedure,

⁃ Participants with a social security in compliance with the French law.