Trial Title:
Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX -Expressing Solid Tumors
NCT ID:
NCT05868174
Condition:
Solid Tumor, Adult
Advanced Solid Tumor
Advanced Renal Cell Carcinoma
Conditions: Official terms:
Neoplasms
Carcinoma, Renal Cell
Peposertib
Conditions: Keywords:
CAIX
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
Dose escalation/de-escalations will be supported by the guidance given by outputs of the
Bayesian model-based dose-escalation design.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
89Zr-TLX250
Description:
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
Arm group label:
89Zr-TLX250, 177Lu-TLX250 and Peposertib
Other name:
89Zr-DFO-girentuximab
Intervention type:
Combination Product
Intervention name:
177Lu-TLX250 and Peposertib
Description:
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.
Arm group label:
89Zr-TLX250, 177Lu-TLX250 and Peposertib
Other name:
177Lu-DOTA-girentuximab
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.
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.
Criteria for eligibility:
Criteria:
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.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Macquarie University
Address:
City:
North Ryde
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Phone:
0000000
Email:
info@telixpharma.com
Investigator:
Last name:
Howard Gurney
Email:
Principal Investigator
Facility:
Name:
Ashford (Icon) Cancer Centre
Address:
City:
Adelaide
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Phone:
00
Email:
info@telixpharma.com
Investigator:
Last name:
Dainik Patel
Email:
Principal Investigator
Facility:
Name:
Princess Alexandra Hospital
Address:
City:
Brisbane
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Phone:
00000000
Email:
info@telixpharma.com
Investigator:
Last name:
Kenneth O'Byrne
Email:
Principal Investigator
Facility:
Name:
Austin Health
Address:
City:
Melbourne
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Princiapl Investigator
Phone:
00000000
Email:
info@telixpharma.com
Investigator:
Last name:
Andrew Scott
Email:
Principal Investigator
Facility:
Name:
GenesisCare Murdoch
Address:
City:
Perth
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Phone:
0000
Email:
info@telixpharma.com
Investigator:
Last name:
Nat Lenzo
Email:
Principal Investigator
Start date:
May 23, 2023
Completion date:
December 2026
Lead sponsor:
Agency:
Telix Pharmaceuticals (Innovations) Pty Limited
Agency class:
Industry
Collaborator:
Agency:
Merck KGaA, Darmstadt, Germany
Agency class:
Industry
Source:
Telix Pharmaceuticals (Innovations) Pty Limited
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05868174
