177Lu-BetaBart in Patients With Relapsed/Refractory, Locally Advanced Inoperable, or Metastatic Solid Tumors

This is a Phase 1/2a dose escalation and expansion study to determine the safety, tolerability, and preliminary clinical activity of 177LuBetaBart, a lutetium-labeled anti-B7-H3 monoclonal antibody, in patients with relapsed/refractory, locally advanced inoperable, or metastatic solid tumors

1. Participants ≥ 18 years of age. 2. Participants with a documented history of histopathologically confirmed CRPC\*, CRC, NSCLC, SCLC, HNSCC, ovarian cancer, cervical cancer, endometrial cancer, TNBC, or ESCC. a. \*Progressive CRPC defined by at least one of the following criteria: i. Two consecutive increases in PSA measured at least 1 week apart. ii. Soft tissue progression defined as a ≥20% increase in the sum of the diameter or the appearance of one or more new lesions by computed tomography (CT)/magnetic resonance imaging (MRI). iii. Progression of bone disease defined by Prostate Cancer Working Group 3 (PCWG3) as evaluable disease or new bone lesions by bone scan. iv. Identification of new soft tissue or bone lesions on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging. b. \*Metastatic disease defined as either or both of the following: i. Documented M1 disease on conventional imaging ii. Identification of bone lesion(s), extra-pelvic soft tissue lesion(s), or visceral metastases on PSMA PET imaging with an FDA-approved imaging agent c. \*Progression following treatment with ADT and at least one ARSI . e. Participants with liver metastases if they meet the following criteria: i. ≤3 lesions ii. All lesions must be ≤2 cm in the short axis iii. SUVmean ≥2 x that of liver parenchyma g. Participants with TNBC if pathology results confirm the following: i. Estrogen receptor expression \ 5 x ULN for participants with known liver metastases * Total bilirubin \> 1.5 x ULN 7. Participants requiring blood product transfusion within 2 weeks of first dose of 177Lu-BetaBart. 8. \*Participants with CRPC who have received prior Lu-177-PSMA radioligand therapy. 9. Clinically significant cardiovascular disease 10. Participation in any other interventional investigational trial 11. Participants who are pregnant or breastfeeding. 12. Major surgery within 4 weeks prior to first dose of 177Lu-BetaBart. 13. Received anti-cancer therapy, including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy or investigational device, ≤ 28 days prior to the first dose of 177Lu-BetaBart. 14. Known active hepatitis B or known active hepatitis C infection. 15. Any uncontrolled intercurrent illness or clinically significant uncontrolled condition(s) 16. Untreated moderate to severe hydronephrosis 17. For CRPC participants, prescence of a superscan by nuclear medicine/99mTc bone scan. 18. Active autoimmune disease that has required systemic treatment within 90 days. 19. Any other clinically significant comorbidities, which in the judgment of the investigator could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the subject to safety risks.