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

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 \<1;

received prior 177Lu-TLX250 therapy, any other radioligand therapy, or any prior CAIX-targeting therapy;

have any known hypersensitivity to compounds of similar chemical or biologic composition to girentuximab, desferrioxamine (DFO) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) linker, zirconium or lutetium, and/or any excipient in the study drug or radiographic contrast-agents;

has received granulocyte colony stimulating factor (G-CSF) or erythropoietin within 4 weeks prior to laboratory evaluations at Screening;

be currently receiving or have received:

* any radionuclide within 10 half-lives of the radionuclide prior to 89Zr-TLX250 administration;

* any type of systemic anticancer therapy within 2 weeks before the first administration of 177Lu-TLX250;

* prior radiotherapy within 2 weeks prior to the first administration of 177Lu-TLX250 (must have recovered from all radiation-related toxicities and not currently require steroid treatment); and/or

* prior palliative radiation (≤2 weeks of radiotherapy) within 1-week of the first administration of 177Lu-TLX250 for non-central nervous system disease; Note: If the investigator feels that the patient is continuing to receive some clinical benefit from standard-of-care (SOC) therapy, the patient may continue SOC therapy up until 2 weeks prior to dosing with 177Lu-TLX250.

have known brain metastases, unless these have been treated and stabilized for at least 4 weeks prior to the first administration of 177Lu-TLX250; Note: Participants with a history of brain metastases must have either a head CT with contrast-or brain MRI performed at Screening to document stable disease prior to the first administration of 177LuTLX250.

Have experienced any major trauma including major surgery (such as abdominal/ cardiac/thoracic surgery) within 3 weeks of administration of the first administration of 177LuTLX250;

be pregnant or intend to become pregnant, breastfeed, or conceive a child during the study period and for at least 42 days after last administration of 89Zr-TLX250 or 6 months after last administration of 177Lu-TLX250, depending on which study drug is administered last to the respective participant;

Note: Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see Appendix 10.4).

be planning to breastfeed during the study period and for 28 days after last administration of 89ZrTLX250 or 75 days after last administration of 177Lu-TLX250, depending on which study drug is administered last to the respective participant;

have active and uncontrolled infections requiring systemic therapy or other severe concurrent disease, which, in the opinion of the investigator, would place the participant at undue risk or interfere with the study;

have a history of concurrent malignancy with a life expectancy of ≤ 2 years or requirement of systemic anti-cancer therapy or requirement of local therapy that would confound study results; however; participants with the following malignancies can be enrolled into the study:

* basal cell or squamous cell carcinoma of the skin;

* carcinoma in situ of the cervix, breast or bladder; and/or

* incidental histologic finding of prostate cancer;

have a serious, non-healing wound, ulcer, or bone fracture;

be unable to stay in the scanner bed with the arms resting out of the thoracic and abdominal fields (i.e., arms alongside the body or raised arm position) for the duration of the scan;

have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 (except for laboratory parameters specified above, Grade 2 alopecia, and/or stable Grade 2 sensory neuropathy, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0;

have inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis, etc.);

have a life expectancy shorter than 3 months;

have bleeding or thrombotic disorders or individuals at risk for severe hemorrhage;

have experienced any clinically significant bleeding, including hemoptysis or tumor bleeding within 2 weeks prior to the first administration of 177Lu-TLX250;

has evidence of a serious active or sub-clinical infection or angina pectoris (New York Heart Association \[NYHA\] Class III or IV), significantly prolonged QT interval or other serious illness(es) involving the cardiac, respiratory, central nervous system, renal, hepatic or hematological organ systems, that might impair the ability to complete this study or could interfere with determination of causality of any adverse effects experienced in this study, or which require treatment that could interact with study treatment; or

have any medical or other condition that in the opinion of the investigator(s) would preclude the individual's participation in a clinical study.

What this study is about