Phase 2a Study to Assess Safety and Efficacy of Two 177Lu-TLX250 Dosing Regimens in Advanced Relapsed or Recurrent ccRCC

Multicenter Phase 2A study of 177Lu-TLX250 in adult participants with CAIX-expressing advanced, relapsed or recurrent clear cell renal cell carcinoma (ccRCC). Part 1 will evaluate two dosing regimens to determine the recommended Phase 3 dose (RP3D).

Inclusion Criteria: * be aged ≥ 18 years. * have provided written informed consent, dated and signed by the participant prior to any study-specific procedure; * have relapsed or recurrent, locally advanced, or metastatic RCC with histologically or cytologically confirmed diagnosis of RCC with clear cell component per American Joint Committee on Cancer Staging Manual (Edge SB et al., 2017), with or without sarcomatoid features; * have received at least 2 and no more than 3 prior lines of systemic therapies for locally advanced or metastatic ccRCC including a PD-1/PD-L1 inhibitor (at least 2 administrations) and a VEGF/VEGFR-targeting agent (including TKI or mAb) in sequence or in combination; * have had radiographic disease progression occurring during or after the most recent line of therapy or intolerance to most recent line of therapy; * have at least one measurable lesion according to RECIST, version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions; * be CAIX-positive at Screening defined as having at least 1 lesion with a tumor-lesion CAIX ratio of the maximum standardized uptake value (SUVmax) to liver mean standardized uptake value SUVmean) ≥ 1.5 as determined by BICR of 89Zr-TLX250 PET outcomes; * have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1; * have recovered from the AEs related to prior lines of therapy or returned to baseline with the exception of Grade 2 neurotoxicity. Ongoing, controlled AEs, such as hypothyroidism or hypertension, are permitted; * have adequate organ function, defined as: * Bone Marrow: * leukocytes ≥ 3,000/µL; * absolute neutrophil count ≥ 1500/µL (administration of granulocyte colony stimulating factor is not allowed within 4 weeks prior to the first administration of 177Lu-TLX250; * platelets ≥ 100,000/µL (platelet transfusion is not allowed within 4 weeks prior to the first administration of 177Lu-TLX250); and * hemoglobin ≥ 9g/dL (red blood cell transfusion is not allowed within 2 weeks prior to the first administration of 177Lu-TLX250). * Liver Function: * total bilirubin ≤ 1.5 × the upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤ 3 × ULN is permitted; and * alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5.0 × ULN for participants with liver metastases. * Renal Function: * creatinine clearance ≥ 40 mL/min as measured by Cockroft-Gault formula or directly calculated by 24h urine; * have negative pregnancy test for women of childbearing potential (serum); and * Females of childbearing potential must have a negative serum pregnancy test during screening and prior to the dose of the IMP; must not be breast-feeding; and must agree to use a highly effective method of contraception (see Appendix 10.4) during treatment and for 6 months following last dose of the IMP Exclusion Criteria: * have any of the following: * visceral metastatic lesions that are ≥ 1 cm that have a CAIX TLR \< 1; * lytic bone metastatic lesions with a soft tissue component of at least 1 cm with a TLR \< 1; and/or * at least one metastatic lymph node lesion with short axis ≥ 2.5 cm with a TLR \