Phase I/IIa Study of 68GaNOTA-Anti-MMR-VHH2 for PET/CT

PART I:

Inclusion Criteria:

Patients will only be included in the study if they meet all of the following criteria:

• Patients who have given informed consent

• Patients at least 18 years old

• Patients with local, locally advanced or metastatic disease of a malignant solidtumor. In order to minimize partial volume effect the diameter of at least 1 tumorlesion should be ≥ 10 mm in short axis for invaded adenopathies and ≥ 10 mm in longaxis for all other types of lesions.

Exclusion Criteria:

Patients will not be included in the study if one of the following criteria applies:

• Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher

• Pregnant patients

• Breast feeding patients

• Patients with abnormal liver (Bilirubin ≥1.5 x ULN, ALT (SGPT) ≥3 x ULN) or kidneyfunction (Serum creatinine clearance ≤50 ml/min as calculated with Cockcroft-Gaultformula)

• Patients with recent (< 1 week) gastrointestinal disorders (CTCAE v4.0 grade 3 or 4)with diarrhea as major symptom

• Patients with any serious active infection

• Patients who have any other life-threatening illness or organ system dysfunction,which in the opinion of the investigator would either compromise patient safety orinterfere with the evaluation of the safety of the test radiopharmaceutical

• Patients who cannot communicate reliably with the investigator

• Patients who are unlikely to cooperate with the requirements of the study

• Patients who are unwilling and/or unable to give informed consent

• Patients at increased risk of death from a pre-existing concurrent illness

• Patients who participated already in this study

PART II:

Inclusion Criteria:

Patients will only be included in the study if they meet all of the following criteria:

• Patients who have given informed consent

• Patients at least 18 years old

• Patients diagnosed with a local, locally advanced or metastatic disease, with any ofthe following cancer types :

• Triple-negative breast carcinoma,

• Hormone-receptor negative (HR-), HER2+ breast carcinoma, with HER2-expressiondefined as HER2+ on ISH or 3+ on IHC, as determined by local assessment on any ofthe available cancer tissues

• Melanoma

• Patients who have had a biopsy of at least one lesion or who are planned to undergostandard-of-care resection or biopsy of at least one lesion, in order to minimizepartial volume effect, the diameter of that lesion should be ≥ 10 mm in short axisfor invaded adenopathies and ≥ 10 mm in long axis for all other types of lesions.

Exclusion Criteria:

Patients will not be included in the study if one of the following criteria applies:

• Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher

• Pregnant patients

• Breast feeding patients

• Patients with recent (< 1 week) gastrointestinal disorders (CTCAE v4.0 grade 3 or 4)with diarrhea as major symptom

• Patients with any serious active infection

• Patients who have any other life-threatening illness or organ system dysfunction,which in the opinion of the investigator would either compromise patient safety orinterfere with the evaluation of the safety of the test radiopharmaceutical

• Patients who cannot communicate reliably with the investigator

• Patients who are unlikely to cooperate with the requirements of the study

• Patients who are unwilling and/or unable to give informed consent

• Patients at increased risk of death from a pre-existing concurrent illness

• Patients who participated already in this study