Clinical Trial · NCT07870746

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

Overview

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).

Sponsor

Telix Pharmaceuticals

Phase

Phase 2

Contacts

Prson Gautam, PhD (CONTACT)

prson.gautam@telixpharma.com

19196508158

ClinicalTrials.gov

NCT07870746

Drug / Compound

TLX250

Isotope(s):

Target(s):

CAIX

Ligand Class: Antibodies

Chelator: DOTA

Eligibility

Inclusion

total bilirubin ≤ 1.5 × the upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤ 3 × ULN is permitted; and
leukocytes ≥ 3,000/µL;
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;
creatinine clearance ≥ 40 mL/min as measured by Cockroft-Gault formula or directly calculated by 24h urine;
hemoglobin ≥ 9g/dL (red blood cell transfusion is not allowed within 2 weeks prior to the first administration of 177Lu-TLX250).
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;
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 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;
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5.0 × ULN for participants with liver metastases.
Renal Function:
have adequate organ function, defined as:
have had radiographic disease progression occurring during or after the most recent line of therapy or intolerance to most recent line of therapy;
Liver Function:
platelets ≥ 100,000/µL (platelet transfusion is not allowed within 4 weeks prior to the first administration of 177Lu-TLX250); and
have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1;
have negative pregnancy test for women of childbearing potential (serum); and
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;
Bone Marrow:
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
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;

Exclusion

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 any of the following:
any radionuclide within 10 half-lives of the radionuclide prior to 89Zr-TLX250 administration;
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;
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;
at least one metastatic lymph node lesion with short axis ≥ 2.5 cm with a TLR \<1;
visceral metastatic lesions that are ≥ 1 cm that have a CAIX TLR \< 1;
has received granulocyte colony stimulating factor (G-CSF) or erythropoietin within 4 weeks prior to laboratory evaluations at Screening;
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:
received prior 177Lu-TLX250 therapy, any other radioligand therapy, or any prior CAIX-targeting therapy;
basal cell or squamous cell carcinoma of the skin;
have bleeding or thrombotic disorders or individuals at risk for severe hemorrhage;
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.
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 any medical or other condition that in the opinion of the investigator(s) would preclude the individual's participation in a clinical study.
have a serious, non-healing wound, ulcer, or bone fracture;
lytic bone metastatic lesions with a soft tissue component of at least 1 cm with a TLR \< 1; and/or
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
any type of systemic anticancer therapy within 2 weeks before the first administration of 177Lu-TLX250;
have experienced any clinically significant bleeding, including hemoptysis or tumor bleeding within 2 weeks prior to the first administration of 177Lu-TLX250;
carcinoma in situ of the cervix, breast or bladder; and/or
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;
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;
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
be currently receiving or have received:
Note: Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see Appendix 10.4).
have a life expectancy shorter than 3 months;
have inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis, etc.);
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.

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