A Study of 177Lu-FAP-2286 in Advanced Solid Tumors

Eligibility Criteria

• 1. Have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved Informed Consent Form (ICF) prior to any study-specific evaluation.
• 2. Be ≥ 18 years of age at the time the ICF is signed.
• 3. Have consented to submission of fresh or archival tumor tissue, if available.
• 4. Have adequate organ function confirmed by the following laboratory values obtained within the Screening Period prior to administration of \[68Ga\]Ga FAP 2286 and prior to first cycle of chemotherapy in the combination groups:
• 5. Have an Eastern Oncology Group (ECOG) performance status of 0 or 1.
• 6. Have a life expectancy of ≥ 6 months.
• 7. Have measurable disease per RECIST v1.1 meeting the following criteria:
• 1. At least 1 lesion of ≥ 10 mm in the longest diameter for a non lymph node or ≥ 15 mm in the short axis diameter for a lymph node that is serially measurable according to RECIST v1.1 using conventional CT and/or MRI.
• 8. Have a histologically and/or cytologically confirmed advanced/metastatic solid tumor not amenable to treatment with curative intent:
• 9. Have cytologically or histologically and radiologically confirmed recurrent or metastatic disease as outlined below:
• * Participants must have progressed on at least one line of hormone-based therapy (either alone or in combination) and at least one, but not more than two lines of chemotherapy (including cytotoxic, targeted and/or anti-drug conjugate therapies) for metastatic disease.
• * Participants must have progressed on at least two lines of cytotoxic chemotherapy (including cytotoxic, anti-drug conjugate, targeted therapies and/or IO) for metastatic disease.
• 1. Active malignancy except for the specific cancer under investigation in this study, ie, participant known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment with the following exceptions:
• 1. History of second malignancy that has been successfully treated, with no evidence of active cancer for 3 years prior to enrollment;
• 2. Surgically cured low-risk tumors, such as early-stage cervical or endometrial cancer, any cancer in situ, or non-melanoma skin cancers; and
• 3. Prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• 2. Symptomatic and/or untreated CNS metastases or leptomeningeal disease or with primary tumor of CNS origin.
• 3. Received anticancer treatment with chemotherapy, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs ≤ 14 days prior (≤ 28 days prior in case of checkpoint inhibitor therapy and other antibody therapies) to the administration of \[177Lu\]Lu FAP 2286.
• 4. Received prior radiopharmaceutical therapy (eg, radium 223 223Ra-dichloride, \[177Lu\]Lu-DOTA-TATE, \[177Lu\]Lu-prostate-specific membrane antigen (PSMA)-617, actinium 225 \[225Ac\]Ac PSMA-617, etc.) or prior EBRT to more than 25% of the bone marrow or received any prior EBRT directly to kidney, or received any EBRT within 2 weeks prior to administration of \[177Lu\]Lu FAP 2286.
• * Prior administration of a radiopharmaceutical unless 10 or more half-lives have elapsed before injection/infusion of \[68Ga\]Ga-FAP-2286 or \[177Lu\]Lu FAP 2286.
• 5. Ongoing adverse effects from anticancer treatment NCI-CTCAE v5.0 (or higher) Grade 1, with the exception for alopecia and vitiligo.
• 1. Clinically significant and/or uncontrolled cardiac disease such as congestive heart failure requiring treatment (New York Heart Association \> Class 2), uncontrolled hypertension, clinically significant arrhythmia, or congenital prolonged QT syndrome;
• 2. Corrected QT interval (Fridericia's formula) \> 450 msec for males or \> 470 msec for females at Screening; or
• 3. Acute coronary syndrome or acute myocardial infarction ≤ 6 months prior to administration of \[177Lu\]Lu FAP 2286.
• 9. Active severe urinary incontinence, severe voiding dysfunction, or urinary obstruction requiring an indwelling/condom catheter that, in the judgment of the investigator, could prevent adhering to radiation safety instructions.
• 10. Severe chronic or active HIV infection:
• 14. The following are exclusion criteria, as applicable:
• 15. Significant weight loss (\> 10% of body weight) within 28 days prior to providing informed consent for this study.
• 16. Presence of any other condition that may increase the risk associated with study participation or interfere with the interpretation of study results, and, in the opinion of the investigator, would make the participant inappropriate for entry into the study.
• 17. Inability to complete the needed investigational and standard imaging examinations due to any reason (e.g., severe claustrophobia, inability to lie still for the entire imaging time).
• 18. Participants with known hypersensitivity to the active agent or excipients. 19. Severe chronic or active infections (including active tuberculosis, HBV, or HCV infection) requiring systemic antibacterial, antifungal or antiviral therapy within 2 weeks before enrollment.