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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05868174




Registration number
NCT05868174
Ethics application status
Date submitted
24/04/2023
Date registered
22/05/2023
Date last updated
1/05/2024

Titles & IDs
Public title
Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX -Expressing Solid Tumors
Scientific 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
Secondary ID [1] 0 0
177Lu-TLX250-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor, Adult 0 0
Advanced Solid Tumor 0 0
Advanced Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Diagnosis / Prognosis - 89Zr-TLX250
Combination Product - 177Lu-TLX250 and Peposertib

Experimental: 89Zr-TLX250, 177Lu-TLX250 and Peposertib - 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.


Diagnosis / Prognosis: 89Zr-TLX250
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

Combination Product: 177Lu-TLX250 and Peposertib
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.
Intervention code [1] 0 0
Diagnosis / Prognosis
Intervention code [2] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety parameter Dose Limited Toxicity (DLT)
Timepoint [1] 0 0
42 days
Primary outcome [2] 0 0
Safety parameter Laboratory Examinations
Timepoint [2] 0 0
42 days
Primary outcome [3] 0 0
Safety parameter Vital signs
Timepoint [3] 0 0
42 days
Primary outcome [4] 0 0
Safety parameter ECG
Timepoint [4] 0 0
42 days
Primary outcome [5] 0 0
Safety parameter Adverse Events and Treatment-Related Adverse Events
Timepoint [5] 0 0
42 days
Primary outcome [6] 0 0
Disease impact causing changes in Eastern Cooperative Oncology Group (ECOG) Performance scale.
Timepoint [6] 0 0
Screening/Baseline, Day1, Day 29, D57 and End of Treatment
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Every 3 months ± 2 weeks for 24 months after the last 177Lu-TLX250 administration
Secondary outcome [2] 0 0
Tumor objective response rate (ORR)
Timepoint [2] 0 0
Every 3 months ± 2 weeks for 12 months after the last 177Lu-TLX250 administration
Secondary outcome [3] 0 0
Progression-free survival (PFS)
Timepoint [3] 0 0
Every 3 months ± 2 weeks for 12 months after the last 177Lu-TLX250 administration
Secondary outcome [4] 0 0
Immunogenicity by formation of ADA(HACA) in blood
Timepoint [4] 0 0
84 days

Eligibility
Key inclusion criteria
- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/05/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Macquarie University - North Ryde
Recruitment hospital [2] 0 0
Ashford (Icon) Cancer Centre - Adelaide
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [4] 0 0
Austin Health - Melbourne
Recruitment hospital [5] 0 0
GenesisCare Murdoch - Perth
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- Perth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Telix Pharmaceuticals (Innovations) Pty Limited
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05868174
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
MEDICAL DIRECTOR, MD
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05868174