Solid Tumor, AdultPhase 1NCT05868174

Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX -Expressing Solid Tumors

A Phase 1 study testing 89Zr-TLX250 and 177Lu-TLX250 and Peposertib in people with Solid Tumor, Adult and Advanced Solid Tumor, run by Telix Pharmaceuticals (Innovations) Pty Limited at 5 sites in Australia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

This is an open label, single-arm, multicentre dose escalation (Part 1) and dose expansion (Part 2) study to evaluate different combinations of 3 radioactive dose levels of 177Lu-TLX250 administered intravenously with 3 different doses of peposertib in patients with CAIX-expressing solid tumors. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Solid Tumor, Adult, Advanced Solid Tumor, Advanced Renal Cell Carcinoma
What is being tested?: 89Zr-TLX250 and 177Lu-TLX250 and Peposertib
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 5 sitesAustralia
Study dates: 23 May 2023to Dec 2026
Phase: Phase 1
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Histologically confirmed advanced or metastatic solid tumor that has progressed on or during/after recognized standard of care therapies and are not eligible for resection, or patients that are not eligible or not consenting to recognized standard of care therapies.
At least one measurable lesion on CT/MRI according to RECIST 1.1 with corresponding 89Zr-TLX250 uptake (i.e., CAIX positive).
CAIX positivity in at least 75% of the total lesion volume (defined as 89Zr- TLX250 uptake with intensity significantly greater than normal liver [i.e., standardized uptake value [SUV]max at least 1.5 times SUV of normal liver]).
ECOG status 0 or 1.
Have adequate organ function during screening
Must have a life expectancy of at least 6 months.

Who cannot join

Prior 177Lu-TLX250 or other radioligand therapy; or any prior CAIX targeting therapy.
Known hypersensitivity to compounds of similar chemical or biologic composition to peposertib, girentuximab radiolabelled by zirconium or lutetium, any excipient in the study medication or any other intravenously administered human proteins/peptides/antibodies.
Administration of any radionuclide within 10 half-lives of the radionuclide prior to signature of the ICF.
Patients who have had chemotherapy, definitive radiation, biological cancer therapy, or investigational agent/device within 28 days of first planned dose of study therapy.
Patients who had > 2 prior lines of cytotoxic chemotherapy or had Grade 4 neutropenia or Grade 3/Grade 4 thrombocytopenia (both of a duration of at least 48 hours) during the last line of therapy. Note: This criterion may be removed in total or in part by the SRC upon review of the safety data from the initial dose level(s).
Patients who cannot discontinue concomitant medications or herbal supplements that are strong inhibitors or strong inducers of cytochrome P450 (CYP) isoenzymes CYP3A4/5, CYP2C9, and CYP2C19. Concomitant use of CYP3A4/5 substrates with a narrow therapeutic index are also excluded.

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Patients who cannot discontinue concomitant H2-blockers or proton-pump inhibitors (PPIs). Patients may confer with the investigator to determine if such medications can be discontinued. These must be discontinued ≥ 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate.
Patients who are receiving therapeutic doses of anticoagulation, including but not limited to low-molecular weight heparin in therapeutic dosing or platelet aggregation inhibitors. Note: This criterion may be removed by the SRC upon review of the safety data from the initial dose level(s).
Patients with ≥ 5 bone metastases and/or bulky (> 3cm in diameter) pelvic or femoral tumors, and/or metastases/tumor in the vertebral spine involving > 3 vertebrae.
Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator.
Presence of active and uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
Requirement of concurrent use of other anti-cancer treatments or agents other than study medications. Supportive care therapies are permitted.

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

MEDICAL DIRECTOR, MD contact

City, postcode or hospital

Sites recruiting now only

5 sites in 1 country

Australia5 sites, 5 recruiting

Ashford (Icon) Cancer Centre
Adelaide
Principal Investigator, 00, info@telixpharma.com
Dainik Patel
Recruiting
Princess Alexandra Hospital
Brisbane
Principal Investigator, 00000000, info@telixpharma.com
Kenneth O'Byrne
Recruiting
Austin Health
Melbourne
Princiapl Investigator, 00000000, info@telixpharma.com
Andrew Scott
Recruiting
Macquarie University
North Ryde, New South Wales
Principal Investigator, 0000000, info@telixpharma.com
Howard Gurney
Recruiting
GenesisCare Murdoch
Perth
Principal Investigator, 0000, info@telixpharma.com
Nat Lenzo
Recruiting

Other trials in Australia

About this study

Official title: A Phase 1b Dose Escalation/Expansion Study of the Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX (CAIX)-Expressing Solid Tumors

Read the detailed description

Part 1 (dose escalation) will evaluate the combination of 3 different activities of 177Lu-TLX250 and 3 different dose levels of peposertib.

Patients with CAIX positive solid tumors will be enrolled in a given dose/activity level in Cohorts of approximately 2-6 patients.

Treatment cycles will have a fixed length of 84 days. Patients will be treated during 3 cycles, or until clinically significant progression or unacceptable toxicity.

Part 2 (dose expansion) patients will be enrolled in 2 Cohorts:

Cohort A: 40 patients with metastatic or non-resectable ccRCC
Cohort B: 20 patients with CAIX-positive solid tumors (excluding RCC).

Patients will be treated at the Recommended phase 2 dose of 177Lu-TLX250 in combination with peposertib at the dosing schedule of the selected Recommended phase 2 dose.

Conditions: Solid Tumor, Adult, Advanced Solid Tumor, Advanced Renal Cell Carcinoma
Being tested: 89Zr-TLX250, 177Lu-TLX250 and Peposertib
Keywords: CAIX

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

89Zr-TLX250Diagnostic test
Also called 89Zr-DFO-girentuximab
Single IV administration followed by 89Zr-DFO-girentuximab PET/CT (or PET/MRI) scan at screening and approximately 8-10 weeks (±1 week) after Cycle 3 Day 1, as well as at the end of treatment visit (if feasible). The PET/CT should be obtained within 4-7 days after 89Zr-TLX250 administration
177Lu-TLX250 and PeposertibCombination product
Also called 177Lu-DOTA-girentuximab
Dose escalation and de-escalation for the determination of the Maximum tolerated combination/ Recommended phase 2 dose.
All subjects will receive 177Lu-TLX250 intravenously on day 1 and Peposertib BID on days 4-21 of each 84-day cycle.

Study groups in NCT05868174
Study group	Role	What they receive
89Zr-TLX250, 177Lu-TLX250 and Peposertib	Experimental	Diagnostic test: A single IV administration of 37 Megabecquerel (+/- 10%) 89Zr-DFO-girentuximab, containing a mass dose of 10 mg of girentuximab, followed by a diagnostic scan Treatment test: A single IV administration that could be 1887 - 2516 or 3145 Megabecquerel (+/- 10%) 177Lu-DOTA-girentuximab,containing a mass dose of 10 mg of girentuximab, on Day 1 of each 84-day cycle and p.o. administration of that could be 100-150 or 200 mg Peposertib BID on days 4-21 of each 84-day cycle. Receives: Diagnostic Test: 89Zr-TLX250; Combination Product: 177Lu-TLX250 and Peposertib

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety parameter Dose Limited Toxicity (DLT)
Dose level toxicity evaluation using Partial Ordering Bayesian Logistic Regression Model Method (PO-BLRM)
Measured: 42 days
Safety parameter Laboratory Examinations
Frequency of occurrence and severity of abnormal findings in safety investigations regarding Laboratory examinations
Measured: 42 days
Safety parameter Vital signs
Frequency of occurrence and severity of abnormal findings in safety investigations regarding the vital signs
Measured: 42 days
Safety parameter ECG
Frequency of occurrence and severity of abnormal findings in the 12-lead ECG (ECG QT interval)
Measured: 42 days
Safety parameter Adverse Events and Treatment-Related Adverse Events
Assessment of AEs graded by the Common Terminology Criteria for Adverse Events (CTCAE) Criteria, Version 5.0
Measured: 42 days
Disease impact causing changes in Eastern Cooperative Oncology Group (ECOG) Performance scale.
Quality of life ( in terms of their ability to care for themself, daily activity, and physical ability (walking, working) is to be evaluated using the ECOG Performance Scale.
Measured: Screening/Baseline, Day1, Day 29, D57 and End of Treatment

Secondary outcomes (4)

Overall Survival (OS)
Overall Survival (OS), determined from enrollment , until death from any cause
Measured: Every 3 months ± 2 weeks for 24 months after the last 177Lu-TLX250 administration
Tumor objective response rate (ORR)
Tumor response in terms of objective response rate (ORR) (solid tumor tissue response and overall radiological response [tumor response by RECIST 1.1 and overall radiological response by RECIST 1.1])
Measured: Every 3 months ± 2 weeks for 12 months after the last 177Lu-TLX250 administration
Progression-free survival (PFS)
Progression free survival (PFS) defined as the time from enrollment to disease progression confirmed by radiology, clinical progression or death (whichever comes first)
Measured: Every 3 months ± 2 weeks for 12 months after the last 177Lu-TLX250 administration
Immunogenicity by formation of ADA(HACA) in blood
This outcome will be measured by analyzing the incidence of ADA(HACA) formation in blood on day 1, day 22, Day 43, Day 57 of each cycle (each cycle is 84 days) and at the end of treatment visit.
Measured: 84 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 May 2023Dec 2026

First posted22 May 2023
Study start23 May 2023
Primary completionDec 2024 (estimated)
Study completionDec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Model description: Dose escalation/de-escalations will be supported by the guidance given by outputs of the Bayesian model-based dose-escalation design.
Masking: None (open label)
Enrolment: 36 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05868174
Sponsor's protocol ID: 177Lu-TLX250-001
Status last verified: Apr 2024
First submitted: 24 Apr 2023
Last updated: 1 May 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Johnstone CN, Osellame LD, Cao Z, McDonald AF, Rigopoulos A, Burvenich IJG, Wichmann CW, Guo N, Ivashkevich AN, Wheatcroft MP, Yan EB, Zimmermann A, Zenke FT, Sirrenberg C, Scott FE, Scott AM. DNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of 177Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma. J Nucl Med. 2025 Mar 3;66(3):385-390. doi: 10.2967/jnumed.124.268695.
PubMed 39884775

Interested in taking part?

MEDICAL DIRECTOR, MD

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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All Solid Tumor, Adult trials

Study at a glance

From the registry record, last updated by the sponsor on 1 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b Dose Escalation/Expansion Study of the Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX (CAIX)-Expressing Solid Tumors
ClinicalTrials.gov ID: NCT05868174
Acronym / sponsor ID: 177Lu-TLX250-001
Conditions: Solid Tumor, Adult, Advanced Solid Tumor, Advanced Renal Cell Carcinoma
Keywords: CAIX
Phase: Phase 1
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 36 participants (estimated)
Lead sponsor: Telix Pharmaceuticals (Innovations) Pty LimitedIndustry (pharma, biotech, devices)
Collaborators: Merck KGaA, Darmstadt, Germany
Study start: 23 May 2023 (actual)
Primary completion: Dec 2024 (estimated)
Study completion: Dec 2026 (estimated)
First posted: 22 May 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Part 1 (dose escalation) will evaluate the combination of 3 different activities of 177Lu-TLX250 and 3 different dose levels of peposertib.

Patients with CAIX positive solid tumors will be enrolled in a given dose/activity level in Cohorts of approximately 2-6 patients.

Treatment cycles will have a fixed length of 84 days. Patients will be treated during 3 cycles, or until clinically significant progression or unacceptable toxicity.

Part 2 (dose expansion) patients will be enrolled in 2 Cohorts:

Cohort A: 40 patients with metastatic or non-resectable ccRCC
Cohort B: 20 patients with CAIX-positive solid tumors (excluding RCC).

Patients will be treated at the Recommended phase 2 dose of 177Lu-TLX250 in combination with peposertib at the dosing schedule of the selected Recommended phase 2 dose.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1
Model description: Dose escalation/de-escalations will be supported by the guidance given by outputs of the Bayesian model-based dose-escalation design.

Arm	Type	Receives
89Zr-TLX250, 177Lu-TLX250 and Peposertib	Experimental	Diagnostic Test: 89Zr-TLX250, Combination Product: 177Lu-TLX250 and PeposertibDiagnostic test: A single IV administration of 37 Megabecquerel (+/- 10%) 89Zr-DFO-girentuximab, containing a mass dose of 10 mg of girentuximab, followed by a diagnostic scan Treatment test: A single IV administration that could be 1887 - 2516 or 3145 Megabecquerel (+/- 10%) 177Lu-DOTA-girentuximab,containing a mass dose of 10 mg of girentuximab, on Day 1 of each 84-day cycle and p.o. administration of that could be 100-150 or 200 mg Peposertib BID on days 4-21 of each 84-day cycle.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Histologically confirmed advanced or metastatic solid tumor that has progressed on or during/after recognized standard of care therapies and are not eligible for resection, or patients that are not eligible or not consenting to recognized standard of care therapies.
At least one measurable lesion on CT/MRI according to RECIST 1.1 with corresponding 89Zr-TLX250 uptake (i.e., CAIX positive).
CAIX positivity in at least 75% of the total lesion volume (defined as 89Zr- TLX250 uptake with intensity significantly greater than normal liver [i.e., standardized uptake value [SUV]max at least 1.5 times SUV of normal liver]).
ECOG status 0 or 1.
Have adequate organ function during screening

Key exclusion criteria (12 listed)

Prior 177Lu-TLX250 or other radioligand therapy; or any prior CAIX targeting therapy.
Known hypersensitivity to compounds of similar chemical or biologic composition to peposertib, girentuximab radiolabelled by zirconium or lutetium, any excipient in the study medication or any other intravenously administered human proteins/peptides/antibodies.
Administration of any radionuclide within 10 half-lives of the radionuclide prior to signature of the ICF.
Patients who have had chemotherapy, definitive radiation, biological cancer therapy, or investigational agent/device within 28 days of first planned dose of study therapy.
Patients who had > 2 prior lines of cytotoxic chemotherapy or had Grade 4 neutropenia or Grade 3/Grade 4 thrombocytopenia (both of a duration of at least 48 hours) during the last line of therapy. Note: This criterion may be removed in total or in part by the SRC upon review of the safety data from the initial dose level(s).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
89Zr-TLX250Also: 89Zr-DFO-girentuximabSingle IV administration followed by 89Zr-DFO-girentuximab PET/CT (or PET/MRI) scan at screening and approximately 8-10 weeks (±1 week) after Cycle 3 Day 1, as well as at the end of treatment visit (if feasible). The PET/CT should be obtained within 4-7 days after 89Zr-TLX250 administration	Diagnostic test	89Zr-TLX250, 177Lu-TLX250 and Peposertib
177Lu-TLX250 and PeposertibAlso: 177Lu-DOTA-girentuximabDose escalation and de-escalation for the determination of the Maximum tolerated combination/ Recommended phase 2 dose. All subjects will receive 177Lu-TLX250 intravenously on day 1 and Peposertib BID on days 4-21 of each 84-day cycle.	Combination product	89Zr-TLX250, 177Lu-TLX250 and Peposertib

Primary outcome

Safety parameter Dose Limited Toxicity (DLT)
Time frame: 42 days
Dose level toxicity evaluation using Partial Ordering Bayesian Logistic Regression Model Method (PO-BLRM)
Safety parameter Laboratory Examinations
Time frame: 42 days
Frequency of occurrence and severity of abnormal findings in safety investigations regarding Laboratory examinations
Safety parameter Vital signs
Time frame: 42 days
Frequency of occurrence and severity of abnormal findings in safety investigations regarding the vital signs
Safety parameter ECG
Time frame: 42 days
Frequency of occurrence and severity of abnormal findings in the 12-lead ECG (ECG QT interval)
Safety parameter Adverse Events and Treatment-Related Adverse Events
Time frame: 42 days
Assessment of AEs graded by the Common Terminology Criteria for Adverse Events (CTCAE) Criteria, Version 5.0
Disease impact causing changes in Eastern Cooperative Oncology Group (ECOG) Performance scale.
Time frame: Screening/Baseline, Day1, Day 29, D57 and End of Treatment
Quality of life ( in terms of their ability to care for themself, daily activity, and physical ability (walking, working) is to be evaluated using the ECOG Performance Scale.

4 secondary outcomes

Overall Survival (OS)
Time frame: Every 3 months ± 2 weeks for 24 months after the last 177Lu-TLX250 administration
Tumor objective response rate (ORR)
Time frame: Every 3 months ± 2 weeks for 12 months after the last 177Lu-TLX250 administration
Progression-free survival (PFS)
Time frame: Every 3 months ± 2 weeks for 12 months after the last 177Lu-TLX250 administration
Immunogenicity by formation of ADA(HACA) in blood
Time frame: 84 days

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2024.
Derived from this study: PubMed 39884775Johnstone CN, Osellame LD, Cao Z, McDonald AF, Rigopoulos A, Burvenich IJG, Wichmann CW, Guo N, Ivashkevich AN, Wheatcroft MP, Yan EB, Zimmermann A, Zenke FT, Sirrenberg C, Scott FE, Scott AM. DNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of 177Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma. J Nucl Med. 2025 Mar 3;66(3):385-390. doi: 10.2967/jnumed.124.268695.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

MEDICAL DIRECTOR, MD contact

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact MEDICAL DIRECTOR, MD, or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety parameter Dose Limited Toxicity (DLT) (time frame: 42 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05868174, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2024.