Phase 3 Study to Assess Safety and Efficacy of 177Lu-TLX250 in Advanced Relapsed or Recurrent ccRCC

NCT07197580 | Recruiting Phase 3 DMC

• 1 other identifier: 177Lu-TLX250-302
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief Summary

Multicenter Phase 3 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). Part 2 will compare 177Lu-TLX250 with investigator's choice of monotherapy aligned with Australian standard-of-care.

Conditions

ccRCC; Renal Cell Carcinoma (RCC); Renal Cell Carcinoma (Kidney Cancer); Renal Cell Cancer Metastatic; Renal Cell Cancer, Recurrent; Clear Cell Renal Cell Cancer (ccRCC)

Keywords

Carbonic anhydrase 9; Clear Cell Renal Cell Cancer; Kidney Cancer; ccRCC; CA9; CA-9; CAIX; Girentuximab; CA9 target therapy; Positron-Emission Tomography; Radiation Therapy; Radiopharmaceuticals; Targeted Radiation

Outcome Measures

Primary Outcomes (2)

• Dose Optimization -safety and tolerability

  Part 1 of the study is being done to identify the best dose to use for Part 2 of the study. Assessing adverse events of special interest (AESIs), incidence and severity of treatment-emergent adverse events (TEAEs) and frequency, severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0, seriousness, and relationship of study treatment will be assessed. Laboratory abnormalities will be assessed according to the NCI CTCAE V5.0.

  Through study completion, an average of 1.5 years

• Efficacy- median mPFS

  Primary objective for Part 2 of the study and secondary objective for Part 1. Monitoring disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).

  Through study completion, an average of 2 years

Secondary Outcomes (29)

• Monitoring OS (Overall Survival)

  Through study completion, an average of 2 years

• Monitoring ORR (Objective Response Rate)

  Through study completion, an average of 2 years

• Monitoring DoR (Duration of Response)

  Through study completion, an average of 2 years

• Monitoring DCR (Disease control Rate)

  Through study completion, an average of 2 years

• Evaluate blood radioactive PK parameter- Cmax (maximum plasma concentration)

  Treatment period (4 months)

Study Arms (2)

1887MBq 177Lu-girentuximab tetraxetan

EXPERIMENTAL

3 infusions of 1887 MBq 177Lu-TLX250 at 8-week intervals or 6 infusions of 1258 MBq 177Lu-TLX250 at 4-week intervals (fractionation of 3 doses of 2516 MBq)

Radiation: 177Lu-TLX250

1258 MBq 177Lu-girentuximab tetraxetan

EXPERIMENTAL

6 infusions of 1258 MBq 177Lu-TLX250 at 4-week intervals

Radiation: 177Lu-TLX250

Interventions

177Lu-TLX250 RADIATION

3 infusions of 177Lu-TLX250 at 8-week intervals or 6 infusions 177Lu-TLX250 at 4-week intervals

Also known as: TLX250-Tx, 177Lu girentuximab tetraxetan

1258 MBq 177Lu-girentuximab tetraxetan; 1887MBq 177Lu-girentuximab tetraxetan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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, DFO or DOTA linker, zirconium or lutetium, and/or any excipient in the study drug or radiographic contrast-agents;
• has received 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;

Sponsors & Collaborators

• Telix Pharmaceuticals (Innovations) Pty Limited: lead
• Medpace, Inc.: collaborator

Study Sites (5)

Westmead Hospital

Sydney, New South Wales, 2145, Australia

NOT YET RECRUITING

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

NOT YET RECRUITING

Austin Health

Heidelberg, Victoria, 3084, Australia

NOT YET RECRUITING

Melbourne Theranostic Innovation Centre (MTIC)

Melbourne N., Victoria, 3051, Australia

NOT YET RECRUITING

GenesisCare, Fiona Stanley Hospital (Murdoch)

Murdoch, Washington, 6150, Australia

RECRUITING

Related Publications (2)

• Muselaers CH, Boers-Sonderen MJ, van Oostenbrugge TJ, Boerman OC, Desar IM, Stillebroer AB, Mulder SF, van Herpen CM, Langenhuijsen JF, Oosterwijk E, Oyen WJ, Mulders PF. Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma. Eur Urol. 2016 May;69(5):767-70. doi: 10.1016/j.eururo.2015.11.033. Epub 2015 Dec 23.

  PMID: 26706103 RESULT

• Stillebroer AB, Boerman OC, Desar IM, Boers-Sonderen MJ, van Herpen CM, Langenhuijsen JF, Smith-Jones PM, Oosterwijk E, Oyen WJ, Mulders PF. Phase 1 radioimmunotherapy study with lutetium 177-labeled anti-carbonic anhydrase IX monoclonal antibody girentuximab in patients with advanced renal cell carcinoma. Eur Urol. 2013 Sep;64(3):478-85. doi: 10.1016/j.eururo.2012.08.024. Epub 2012 Aug 21.

  PMID: 22980441 RESULT

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Prson Gautam, PhD

CONTACT

19196508158; prson.gautam@telixpharma.com

Lily Nahidi, PhD

CONTACT

lily.nahidi@telixpharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2025
• First Posted: September 29, 2025
• Study Start: March 25, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): February 28, 2029
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)