Exclusion
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Participants who meet any of the following criteria will be excluded from the study. The criteria below apply to participants enrolling in Phase 1 or Phase 2.
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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:
- History of second malignancy that has been successfully treated, with no evidence of active cancer for 3 years prior to enrollment;
- Surgically cured low-risk tumors, such as early-stage cervical or endometrial cancer, any cancer in situ, or non-melanoma skin cancers; and
- 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.
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Symptomatic and/or untreated CNS metastases or leptomeningeal disease or with primary tumor of CNS origin.
a. Participants with asymptomatic, previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks and have completed RT> 2 weeks prior to treatment. Participants may be on corticosteroids if on a stable dose equivalent to prednisone 10 mg daily or less.
- 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.
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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.
- Ongoing adverse effects from anticancer treatment NCI-CTCAE v5.0 (or higher) Grade 1, with the exception for alopecia and vitiligo.
Exclusion criteria 6 and 7 are removed with Protocol Amendment 7. 8. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- 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;
- Corrected QT interval (Fridericia's formula) > 450 msec for males or > 470 msec for females at Screening; or
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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:
a. Participants on effective antiretroviral therapy with undetectable viral load within 6 months prior to the first dose of [177Lu]Lu FAP 2286 are eligible.
Exclusion criteria 11 and 12 are removed with Protocol Amendment 7. 13. Non-study-related minor surgical procedure ≤ 5 days, or major surgical procedure ≤ 21 days, prior to the administration of [177Lu]Lu FAP 2286; in all cases, the participant must be sufficiently recovered and stable before treatment administration.
14. The following are exclusion criteria, as applicable:
a. Female participants of childbearing potential: i. Refusal to use a highly effective method of contraception or to practice true abstinence during treatment and for 6 months following the last dose of investigational product; ii. Pregnant, suspected pregnancy, or breast feeding; iii. Planning on getting pregnant during treatment and for 6 months following the last dose of investigational product.
b. Male participants with female partners of childbearing potential: i. Refusal to use a highly effective method of contraception or to practice true abstinence during treatment and for 6 months following the last dose of investigational product.
c. All male participants: i. Refusal to use condoms during sex. ii. Planning to make semen donations during treatment and for 6 months following the last dose of investigational product.
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.
Note: Antiviral therapy is permitted for participants with chronic HBV or HCV infection. Participants receiving antivirals at Screening should have been treated for > 2 weeks before enrollment. Inactive hepatitis B surface antigen (HbsAg) carriers treated and stable hepatitis B participants (HBV DNA < 500 IU/mL or < 2500 copies/mL) can be enrolled. Participants with detectable hepatitis B surface antigen (HbsAg) or detectable HBV DNA should be managed per treatment guidelines. Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA.