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

Primary Purpose

Solid Tumor, Adult, Advanced Solid Tumor, Advanced Renal Cell Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
89Zr-TLX250
177Lu-TLX250 and Peposertib
Sponsored by
Telix International Pty Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor, Adult focused on measuring CAIX

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Macquarie University
  • Ashford (Icon) Cancer CentreRecruiting
  • Princess Alexandra Hospital
  • Austin Health
  • GenesisCare MurdochRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

89Zr-TLX250, 177Lu-TLX250 and Peposertib

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety parameter Dose Limited Toxicity (DLT)
Dose level toxicity evaluation using Partial Ordering Bayesian Logistic Regression Model Method (PO-BLRM)
Safety parameter Laboratory Examinations
Frequency of occurrence and severity of abnormal findings in safety investigations regarding Laboratory examinations
Safety parameter Vital signs
Frequency of occurrence and severity of abnormal findings in safety investigations regarding the vital signs
Safety parameter ECG
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
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.
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.

Secondary Outcome Measures

Overall Survival (OS)
Overall Survival (OS), determined from enrollment , until death from any cause
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])
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)
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.

Full Information

First Posted
April 24, 2023
Last Updated
May 22, 2023
Sponsor
Telix International Pty Ltd
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT05868174
Brief Title
Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX -Expressing Solid Tumors
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 23, 2023 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Telix International Pty Ltd
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Adult, Advanced Solid Tumor, Advanced Renal Cell Carcinoma
Keywords
CAIX

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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)
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
89Zr-TLX250, 177Lu-TLX250 and Peposertib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
89Zr-TLX250
Other Intervention Name(s)
89Zr-DFO-girentuximab
Intervention 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
Intervention Type
Combination Product
Intervention Name(s)
177Lu-TLX250 and Peposertib
Other Intervention Name(s)
177Lu-DOTA-girentuximab
Intervention 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.
Primary Outcome Measure Information:
Title
Safety parameter Dose Limited Toxicity (DLT)
Description
Dose level toxicity evaluation using Partial Ordering Bayesian Logistic Regression Model Method (PO-BLRM)
Time Frame
42 days
Title
Safety parameter Laboratory Examinations
Description
Frequency of occurrence and severity of abnormal findings in safety investigations regarding Laboratory examinations
Time Frame
42 days
Title
Safety parameter Vital signs
Description
Frequency of occurrence and severity of abnormal findings in safety investigations regarding the vital signs
Time Frame
42 days
Title
Safety parameter ECG
Description
Frequency of occurrence and severity of abnormal findings in the 12-lead ECG (ECG QT interval)
Time Frame
42 days
Title
Safety parameter Adverse Events and Treatment-Related Adverse Events
Description
Assessment of AEs graded by the Common Terminology Criteria for Adverse Events (CTCAE) Criteria, Version 5.0
Time Frame
42 days
Title
Disease impact causing changes in Eastern Cooperative Oncology Group (ECOG) Performance scale.
Description
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.
Time Frame
Screening/Baseline, Day1, Day 29, D57 and End of Treatment
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall Survival (OS), determined from enrollment , until death from any cause
Time Frame
Every 3 months ± 2 weeks for 24 months after the last 177Lu-TLX250 administration
Title
Tumor objective response rate (ORR)
Description
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])
Time Frame
Every 3 months ± 2 weeks for 12 months after the last 177Lu-TLX250 administration
Title
Progression-free survival (PFS)
Description
Progression free survival (PFS) defined as the time from enrollment to disease progression confirmed by radiology, clinical progression or death (whichever comes first)
Time Frame
Every 3 months ± 2 weeks for 12 months after the last 177Lu-TLX250 administration
Title
Immunogenicity by formation of ADA(HACA) in blood
Description
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.
Time Frame
84 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
MEDICAL DIRECTOR, MD
Facility Information:
Facility Name
Macquarie University
City
North Ryde
State/Province
New South Wales
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Howard Gurney
Facility Name
Ashford (Icon) Cancer Centre
City
Adelaide
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Phone
00
Email
info@telixpharma.com
First Name & Middle Initial & Last Name & Degree
Dainik Patel
Facility Name
Princess Alexandra Hospital
City
Brisbane
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kenneth O'Byrne
Facility Name
Austin Health
City
Melbourne
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Princiapl Investigator
First Name & Middle Initial & Last Name & Degree
Andrew Scott
Facility Name
GenesisCare Murdoch
City
Perth
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Phone
0000
Email
info@telixpharma.com
First Name & Middle Initial & Last Name & Degree
Nat Lenzo

12. IPD Sharing Statement

Learn more about this trial

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

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