Combination of 177Lu-TLX250 and Peposertib in Patients Wi... | NCT05868174

Status Module

Name	Class
Merck KGaA, Darmstadt, Germany	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	Diagnostic Test: 89Zr-TLX250 Combination Product: 177Lu-TLX250 and Peposertib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
89Zr-TLX250	Diagnostic Test	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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety parameter Dose Limited Toxicity (DLT)	Dose level toxicity evaluation using Partial Ordering Bayesian Logistic Regression Model Method (PO-BLRM)	42 days
Safety parameter Laboratory Examinations	Frequency of occurrence and severity of abnormal findings in safety investigations regarding Laboratory examinations	42 days
Safety parameter Vital signs	Frequency of occurrence and severity of abnormal findings in safety investigations regarding the vital signs	42 days
Safety parameter ECG	Frequency of occurrence and severity of abnormal findings in the 12-lead ECG (ECG QT interval)	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	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.	Screening/Baseline, Day1, Day 29, D57 and End of Treatment

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	Overall Survival (OS), determined from enrollment , until death from any cause	Every 3 months ± 2 weeks for 24 months after the last 177Lu-TLX250 administration
Tumor objective response rate (ORR)

Eligibility Module

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.