68Ga-FAPI-46 PET for Imaging of FAP Expressing Cancer

Primary Endpoint:

Positive predictive value (PPV) on a per-region- and per-patient-basis of 68Ga-FAPI-46 PET for detection of histopathology-FAPpositive tumor lesions, confirmed by histopathology/biopsy (reached for ≥ 75%).

Secondary Endpoints:

• Association between 68Ga-FAPI-46 PET uptake intensity and histopathologic FAP expression
• Sensitivity and specificity of 68Ga-FAPI-46 PET on a per-patient and per-region-basis for detection of histopathology-FAPpositive tumor lesions confirmed by histopathology/biopsy (separate for regional, extra-regional and distant locations)
• Detection rate of 68Ga-FAPI-46 PET versus previous standard imaging on a per-patient and per-region-basis for detection of tumor location, also stratified by tumor maker serum level
• Sensitivity and specificity of 68Ga-FAPI-46 PET versus previous standard imaging on a per-patient and per-region-basis for detection of tumor lesions confirmed by combined histopathology/biopsy/follow-up imaging/clinical follow-up reference standard (separate for regional, extra-regional and distant locations)
• Impact on management
• Inter-reader reproducibility
• Safety
• Change in staging/prognostic groups

Inclusion criteria

• Proven or suspected tumor types: Breast, Colorectal, Endometrial, Esophageal, Glioma/GMB, Head and neck, Hepatocellular carcinoma, ,Lymphoma, Multiple Myeloma, Neuroendocrine, NSCLC (Non small cell lung cancer), Ovarian, Pancreatic, Prostate, Renal cell carcinoma, Sarcoma, SCLC (Small cell lung cancer), Semimoma, Thyroid, Unknown primary, Other
• At initial staging or re-staging of disease
• At least one detectable tumor lesion with any diameter >1 cm
• Intended or performed surgery or biopsy of tumor within 8 weeks before or after enrollment
• Age ≥18 years
• Patient Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Women of child bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, can only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test within 24 h before radiopharmaceutical application.

Exclusion criteria

• Patient cannot give consent for the study
• Patient cannot lie flat or tolerate 68Ga-FAPI-46 PET imaging
• Prior external beam radiation therapy (EBRT) within 3 months of enrollment to tumor lesions intended for surgery or biopsy
• Prior chemotherapy, immunotherapy, biologic or targeted oncologic therapy within 3 months of enrollment
• Unwillingness or inability to comply with study and follow-up procedures
• History of disease or condition that may critically interfere with participation in this study at the discretion of the investigators
• Pregnant, lactating, or breast-feeding women
• Women of child bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study, unless they are using highly effective methods of contraception during the interventional period. Highly effective contraception methods include:

• True sexual abstinence: defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of contraception.
• Vasectomised partner is a highly effective birth control method if the partner is the sole sexual partner of the study participant and the vasectomised partner has received medical assessment of the surgical success.
• Bilateral tubal occlusion.
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation:

• oral
• intravaginal
• transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:

• oral
• injectable
• implantable
• Placement of an intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
• Post-menopausal women are allowed to participate in this study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms), or six months of spontaneous amenorrhea with serum folliclestimulating hormone (FSH) levels > 40mIU/mL or have had surgical bilateral oophorectomy or bilateral salpingectomy or hysterectomy or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
• Sexually active males must use a condom during intercourse during the interventional period. A condom is required to be used also by vasectomized men in order to prevent delivery of the study compound via seminal fluid
• QTcF >470 msec for females and QTcF >450 msec for males on screening electrocardiogram (ECG) or history of congenital long QT syndrome.
• Known or expected hypersensitivity to 68Ga-68-FAPI-46 or any of the relevant excipients.