Safety and Early Signs of Efficacy of IL12-L19L19.

Inclusion Criteria:

1. Male or Female aged 18 to 80 years at the time of consent.

2. Patients must have a histological or cytological diagnosis of advanced/metastaticimmunotherapy responsive solid carcinoma for which immune checkpoint blockade isapproved, that has progressed on immune checkpoint-blockade therapy.

3. Patients must have received an immune checkpoint blockade therapy-based regimen asprior treatment.

4. Only patients without other therapeutic alternatives with curative or survivalprolonging potential per investigator judgement are able to participate.

5. Subjects must have had clinical benefit in terms of disease control (CR/PR/SD) whileon checkpoint inhibitor treatment defined as ≥ 3 month free from progression frominitial imaging documenting advanced/metastatic disease followed by radiographicdisease progression after checkpoint inhibitor per investigator's opinion.

6. Patients must have progressive disease or relapse at the time of screening.

7. Patients may have previously received chemotherapy, immunotherapy or radiationtherapy. Such therapies must be completed at least 4 weeks prior to study drugadministration. Radiotherapy within 4 weeks of the first dose of study drug, isallowed for palliative radiotherapy to a limited field, such as for the treatment ofbone pain or a focally painful tumor mass. During the expansion part, to allowevaluation of response to treatment, patients must have remaining measurable diseasethat has not been irradiated.

8. Eastern cooperative oncology group (ECOG) performance status ≤ 2.

9. Patient has an estimated life expectancy of at least 12 weeks.

10. At least one unidimensionally measurable lesion either by computed tomography (CT),MRI or PET/CT as defined by RECIST (v. 1.1) for solid tumors.

11. Documented negative test for HIV-HBV-HCV. For HBV serology: the determination ofHBsAg, and anti-HBcAg-Ab is required. In patients with serology documenting previousexposure to HBV (i.e., anti-HBs Ab with no history of vaccination and/or anti-HBcAb), negative serum HBV-DNA is required. For HCV: HCV-RNA or HCV antibody test.Subjects with a positive test for HCV antibody but no detection of HCV-RNAindicating no current infection are eligible.

12. All acute toxic effects (excluding alopecia and fatigue) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to NationalCancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v. 5.0) Grade ≤ 1.

13. Full resolution of checkpoint blockade therapy-related adverse effects (includingimmune-related adverse effects) and no treatment for these AEs for at least 4 weeksprior to the time of enrollment. The only exception are patients with checkpointblockade induced hypothyroidism and hypophysitis if these patients are on stablemaintenance therapy with on levothyroxine or steroids (≤ 10 mg prednisoneequivalent) for at least 2 months prior dosing.

14. No history of severe immune related adverse effects from prior given immunecheckpoint blockade therapy (CTCAE Grade 4; CTCAE Grade 3 requiring treatment >4weeks).

15. Female patients: negative blood pregnancy test at Screening for women ofchildbearing potential (WOCBP)*. WOCBP must agree to use, from the screening to sixmonths following the last study drug administration, highly effective contraceptionmethods, as defined by the "Recommendations for contraception and pregnancy testingin clinical trials" issued by the Head of Medicine Agencies' Clinical TrialFacilitation Group (www.hma.eu/ctfg.html) and which include, for instance,progesterone-only or combined (estrogen- and progesterone-containing) hormonalcontraception associated with inhibition of ovulation, intrauterine devices,intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomizedpartner.

16. Male patients: male subjects able to father children must agree to use twoacceptable methods of contraception throughout the study (e.g. condom withspermicidal gel). Double-barrier contraception is required.

17. Negative TB test (e.g. Mantoux or Quantiferon assay).

18. A personally signed and dated informed consent document indicating that the subjecthas been informed of all pertinent aspects of the study and has given consent toparticipate in the study.

19. Willingness and ability to comply with the scheduled visits, treatment plan,laboratory tests and other study procedures.

• Women of childbearing potential are defined as females who have experiencedmenarche, are not postmenopausal (12 months with no menses without analternative medical cause) and are not permanently sterilized (e.g., tubalocclusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy)

Exclusion Criteria:

1. Subjects who participated in an investigational drug or device study within 4 weeksprior to study treatment start.

2. Radiotherapy within 4 weeks prior to study treatment start.

3. Active or history of autoimmune disease that might deteriorate when receiving animmuno-stimulatory agent.

4. Patients with primary brain tumors or CNS disease (including brain metastases).

5. Patient taking herbal medications within 7 days prior to study treatment start.

6. Known history of allergy to an excipient in study medication or any otherintravenously administered human proteins/peptides/antibodies.

7. Absolute neutrophil count (ANC) < 1.5 x 10^9/L, platelets < 100 x 10^9/L orhaemoglobin (Hb) < 9.0 g/dl.

8. Chronically impaired renal function as indicated by creatinine clearance < 60 mL/minor serum creatinine > 1.5 ULN.

9. Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 2.0 xULN). At the discretion of the investigator, an increased exclusion threshold forpatients with liver metastasis can be accepted as follows: ALT, AST, ALP andbilirubin ≥ 5 x ULN.

10. Any severe concomitant condition which makes it undesirable for the patient toparticipate in the study or which could jeopardize compliance with the protocol, inthe opinion of the investigator.

11. History within the last year of cerebrovascular disease and/or acute or subacutecoronary syndromes including myocardial infarction, unstable or severe stable anginapectoris.

12. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).

13. Clinically significant cardiac arrhythmias or requiring permanent medication.

14. Abnormal LVEF or any other abnormalities observed during baseline ECG andechocardiogram investigations that are considered as clinically significant by theinvestigator. Subjects with current, or a history of QT/QTc prolongation would beexcluded. In particular:

• patients with a marked prolongation of QT/QTc interval (e.g., repeateddemonstration of QTc >480 milliseconds using Fredricia's QT correction formula)are excluded;

• patients with a history of risk factors for Torsades de Pointes (e.g., heartfailure, hypokalemia, family history of prolonged QT syndrome) are excluded;

• patients who require the use of concomitant medications that prolong the QT/QTcinterval are excluded.

15. Uncontrolled hypertension as defined by systolic blood pressure ≥ 140 mmHg anddiastolic blood pressure ≥ 90 mmHg at 3 consecutive measurements performed withinone week. Note: if the first blood pressure measurement is below threshold forsystolic or diastolic blood pressure, it is not required to repeat the measurement.

16. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaineclassification).

17. Severe diabetic retinopathy such as severe non-proliferative retinopathy andproliferative retinopathy.

18. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery)within 4 weeks of study treatment start.

19. Pregnancy or breast-feeding.

20. Systemic chronic steroid therapy (>10 mg/day prednisone or equivalent) or any otherimmunosuppressive therapy within 14 days prior to study treatment start. Topical,inhaled, nasal and ophthalmic steroids are allowed.

21. Presence of active and uncontrolled infections or other severe concurrent disease,which, in the opinion of the investigator, would place the patient at undue risk orinterfere with the study.

22. Concurrent or previous malignancies (other than the indication for this trial),unless a complete remission without further recurrence was achieved at least 2 yearsprior to study treatment start.

23. Growth factors or immunomodulatory agents within 7 days prior to study treatmentstart.

24. Serious, non-healing wound, ulcer or bone fracture.

25. Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6months.

26. Requirement of concurrent use of other anti-cancer treatments or agents other thanstudy medication.

27. Any recent live vaccination within 4 weeks prior to treatment or plan to receivevaccination during the study.