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 <1%, ii. Progesterone receptor expression <1%, iii. Human epidermal growth factor receptor 2 (HER2) negative, defined as IHC 0 or 1+, or IHC 2+ with negative in situ hybridization (ISH)
3. Participants must have documented disease progression during or after their most recent line of anticancer therapy. Participants must be refractory to or intolerant of standard of care therapy or have no standard of care therapy available that is likely to provide clinical benefit.
4. Must have at least 1 measurable target lesion according to RECIST v1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
6. Participants must have a life expectancy of ≥ 4 months in the opinion of the Investigator.
7. Participants of child-bearing potential (CBP) must have a negative β-hCG test and must not be breastfeeding.
8. Participants of CBP must agree to use a highly effective method of contraception.
9. Participants with previously treated brain metastases are eligible to participate if:
- they are neurologically and radiologically stable for at least 28 days prior to the first dose of 177Lu-BetaBart; and
- have no history of leptomeningeal disease or spinal cord compression.
Exclusion Criteria:
1. History of prior organ transplant.
2. Any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer.
3. Have any medical condition that would, in the Investigator's judgment, prevent the participant's full participation in the clinical study due to safety concerns or compliance with clinical study procedures.
4. Residual toxicity ≥ Grade 2 from prior anti-cancer therapy
5. History of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics.
6. Inadequate organ functions as reflected in laboratory parameters:
- Estimated glomerular filtration rate (eGFR) < 50 mL/min
- Platelet count of < 100 x 109/L
- Absolute neutrophil count (ANC) < 1.5 x 109/L
- Hemoglobin < 9 g/dL
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN), or > 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.