Combining two treatments for patients with certain solid tumors

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

This study is testing if combining a radioactive treatment with another drug can help people with certain solid tumors, like advanced kidney cancer, feel better and improve their condition.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Telix Pharmaceuticals (Innovations) Pty Limited (Industry-sponsored)
• Drugs / interventions: girentuximab, chemotherapy, radiation
• Locations: 5 sites (North Ryde, New South Wales and 4 other locations)
• Trial ID: NCT05868174 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm clinical trial evaluates the safety and efficacy of combining 177Lu-TLX250, a radioactive treatment, with peposertib in patients with carbonic anhydrase IX (CAIX) expressing solid tumors. The study consists of two parts: a dose escalation phase to determine the optimal dosing of both treatments, followed by a dose expansion phase focusing on patients with advanced renal cell carcinoma and other CAIX-positive solid tumors. Patients will receive treatment over three cycles, each lasting 84 days, and will be monitored for progression and toxicity.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced or metastatic solid tumors that are CAIX positive and have progressed on standard therapies.

Not a fit: Patients who have previously received CAIX-targeting therapies or have known hypersensitivity to the treatment components may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with advanced solid tumors that express CAIX.

How similar studies have performed: While this approach is novel in combining these specific treatments, similar studies targeting CAIX have shown promise in the past.

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.

Where this trial is running

North Ryde, New South Wales and 4 other locations

• Macquarie University — North Ryde, New South Wales, Australia (Recruiting)
• Ashford (Icon) Cancer Centre — Adelaide, Australia (Recruiting)
• Princess Alexandra Hospital — Brisbane, Australia (Recruiting)
• Austin Health — Melbourne, Australia (Recruiting)
• GenesisCare Murdoch — Perth, Australia (Recruiting)

Study contacts

• Study coordinator: Medical Director, Md

Conditions Solid Tumor, Adult; Advanced Solid Tumor; Advanced Renal Cell Carcinoma; CAIX