Safety, Tolerability, PK, Dosimetry, MTD and Preliminary Efficacy of Intra-lesionally Injected AvidinOX, Followed by IV Escalating Doses of [177Lu]DOTA-biotin in Pts With Injectable Solid Tumors or Lymphomas

The primary objectives of this study are:

1. To identify the Maximum Tolerated Dose (MTD) of two consecutive repeated IV 177Lu-ST2210
administration following a previous tumor intra-lesion/s injection of AvidinOX.

2. To assess safety and tolerability of intra-lesionally injected AvidinOX + IV injected
177Lu-ST2210

3. To evaluate intra-lesional distribution and retention of {AvidinOX +
177Lu-ST2210}-complex in tumor lesion/s

4. To evaluate systemic biodistribution and pharmacokinetics of 177Lu-ST2210 and {AvidinOX
+ 177Lu-ST2210}- complex

Main secondary objectives are:

1. To evaluate whole body dosimetry of IV 177Lu-ST2210 after prior AvidinOX injection
(radiation safety dosimetry)

2. To record individual tumor dosimetry

3. To evaluate preliminary efficacy of {AvidinOX + 177Lu-ST2210}-complex in reducing tumor
size and metabolic activity.

4. To evaluate damage of tumor cells by radioactivity and immunogenic cell death

5. To evaluate whole body safety dosimetry and dose linearity

6. To evaluate pharmacokinetics of ST2210 in plasma and urine

Main Inclusion Criteria:

- Presence of inoperable tumor lesion/s from histologically confirmed solid tumors or
lymphomas, in patients with at least one lesion ≥ 1 cm and suitable for intra-lesional
injection, who have disease progression after treatment with available therapies, or
who are intolerant to such treatments

- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

- If the patient received previous radiation therapy, the total absorbed radiation dose
at the bone marrow level must be ≤ 1 Gy

- Life expectancy of at least 3 months

- Total tumor burden requiring ≤ 75 mL AvidinOX injection

- Clotting parameters within normal limits or maximum 25% outside of the the normal
ranges

- Haematological and liver function test results ≤ grade 2 toxicity (according to US
National Cancer Institute's Common Terminology) Criteria for Adverse Events v4.03
[CTCAE

- Urine protein (dipstick): negative or trace; in case of trace, a urinalysis has to be
performed in the local laboratory and have to confirm that such abnormality is not to
be considered clinically significant, according to the investigator's judgement

- Creatinine ≤ 1.7 mg/dL

- eGFR> 60% of mean age adjusted normal values

- Written informed consent

Main Exclusion Criteria:

- Known hypersensitivity to Avidin or AvidinOX (e.g. hen egg)

- Known hypersensitivity to ST2210 (DOTA biotin) or any excipient.

- Presence of unreachable (e.g. located in a region that cannot be reached by needle) or
untreatable tumor lesions so that the benefit from the treatment of the treatable
lesions does not justify patient's inclusion

- Active infection at screening or history of severe infection within the previous 3
months, if clinically relevant at screening as considered by the investigator

- Known human immunodeficiency virus (HIV) positive serology or chronically active
hepatitis B or C.

- Administration of another investigational medicinal product within 30 days before the
screening period.

- Patient who underwent chemotherapy, radiation therapy within 15 days before the
screening period

- Previous treatment with any radiopharmaceutical within a period corresponding to 8
half-lives of the radionuclide used for labeling the respective radiopharmaceutical
prior to the administration of study drug.

- Women of child-bearing potential without a serum negative pregnancy test and not
willing to refrain from sexual activity or to utilize an adeguate contraceptive
methods during all the course of the study

- Men unwilling to use appropriate contraceptive methods during the study and up to six
months follow-up period