IRB Study Number 25-960
Status Recruiting
Phases Phase 2, Phase 3
Locations Moll Cancer Center at Fairview Hospital, Hillcrest Hospital, Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
Description
Primary Objective
-To compare the efficacy of iza-bren at the recommended Phase 3 dose (RP3D) vs platinum-based chemotherapy (PBC) in participants with advanced urothelial cancer who are IO experienced
Secondary Objectives
-To assess other measures of efficacy of iza-bren at RP3D vs PBC in participants with advanced urothelial cancer who are IO experienced
-To assess the quality of life (QoL) of participants treated with iza-bren at RP3D vs participants treated with PBC.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria are met:
Signed Written Informed Consent
1) Participants must have signed and dated an IRB/IEC-approved written ICF in accordance with regulatory, local, and institutional guidelines. The study specific ICF and any optional ICFs (if applicable) must be obtained before performing any protocol-related procedures that are not part of normal patient care.
Note: Participants must agree to comply with the requirements and restrictions listed in the informed consent (IC) and in this protocol.
Type of Participant and Target Disease Characteristics
2) Histologically or cytologically documented metastatic or surgically unresectable transitional cell carcinoma (TCC) of the urothelium involving the renal pelvis, ureter, bladder, or urethra. Minor histologic variants (ie, < 50% overall) are acceptable, provided that TCC is the dominant histology.
3) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
4) Participants must have disease progression or recurrence on or following treatment with antiprogrammed cell death protein 1/programmed death-ligand 1 (anti-PD-(L)1)-based therapy), either in combination with or sequential to another systemic therapy (eg, PBC, ADC).
Note: Anti PD-1/PD-L1 therapy administered in a locally advanced or metastatic setting (eg, adjuvant, peri-operative, 1L, 1L maintenance, or 2L), will be considered towards eligibility for the study.
Note: The anti-PD-(L)1-based regimen does not have to be the most recent line of therapy.
Note: Participants who have received anti-PD-(L)1 therapy only in the NMIBC setting are ineligible.
Note: All participants progressing on or after completion of peri-operative treatment are considered to have received 1 prior regimen of therapy. Following disease progression on or after perioperative therapy, further treatment in the advanced disease setting would qualify as a second regimen of therapy even if it is the same treatment used perioperatively. Additionally, switch maintenance therapy with PD-(L)1 inhibitors for advanced disease and switch in therapy due to safety or toxicity reasons unrelated to disease progression are not regarded as additional regimens of therapy.
5) Participants treated only in the peri-operative setting must have relapsed within 12 months of the last dose of treatment.
6) Participants must be eligible for a PBC regimen with cisplatin or carboplatin.
a) Patients must have a platinum-free interval of at least 12 months from the last dose of prior PBC.
b) Patients with progressive disease (PD) or with stable disease (SD) of less than 6-months duration as best overall response on prior platinum-based chemotherapy are ineligible.
7) Radiographically documented disease progression on or after receiving the most recent therapy.
8) Measurable disease as defined by RECIST v1.1.
Note: Bone-only disease is allowed provided it is measurable (ie, with a soft tissue component).
Note: Lesions that have been treated with radiotherapy must show evidence of disease progression based on RECIST v1.1 to be deemed a target lesion.
Note: If there is only 1 measurable lesion, if a biopsy is performed on that lesion, baseline imaging should be performed at least 14 days after the biopsy. Participants must have an MRI of the brain within 28 days prior to randomization if they have known or suspected brain metastases. A CT scan can be used if there is a contraindication to an MRI such as a pacemaker.
Please see protocol for full inclusion criteria
Exclusion Criteria
Participants are excluded from the study if any of the following criteria are met:
Oncologic Medical Conditions
1) Participants with untreated CNS (eg, brain or leptomeningeal) metastases or spinal cord compression.
Note: Participants are eligible if CNS metastases have been definitively treated and are clinically stable or have returned to baseline (except for residual effects from treatment).
Note: Participants must have discontinued corticosteroids or be on a stable/decreasing dose of 10 mg or less of prednisone (or equivalent) daily for at least 2 weeks before initiating treatment.
Note: Baseline imaging required at screening must be performed at least 28 days after definitive treatment for CNS metastases is completed. CNS metastases must be radiographically stable.
2) Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to treatment assignment (ie, participants with a history or prior malignancy are eligible if treatment is completed at least 2 years before treatment assignment and there is no evidence of disease). Participants with a history of prior early-stage cancer including basal/squamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are also eligible if the condition would not confound study results.
Systemic Medical Conditions
3) History of severe heart disease including, but not limited to, any of the following:
a) History of clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification II to IV, or significant pericardial effusion) within 6 months prior to randomization.
b) Myocardial infarction, uncontrolled angina, or stroke/transient ischemic attack within 6 months prior to randomization.
c) QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation ≥ 450 msec for males and ≥ 470 msec for females, except for right bundle branch block (RBBB).
4) Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism, within 2 months prior to screening. Infusion set-related thrombosis is permissible. Participants receiving treatment for a thrombotic event, regardless of etiology, need to be on a stable dose of anticoagulant to be eligible and must have tolerated treatment without clinically significant bleeding or other major sequelae.
5) Participants with known coagulation disorders, including hemophilia, von Willebrand disease, or any other coagulation disorders, that may affect blood clotting.
6) Participants with known hematologic conditions that may affect bone marrow reserve, including but not limited to myelodysplastic syndrome, unexplained anemia, unexplained thrombocytopenia, or a history of immune thrombocytopenia.
7) Prior history of clinically significant bleeding, or perforation of the gastrointestinal tract within 6 months of randomization.
8) Participants with advanced/ clinically significant lung disease (eg, poorly controlled chronic obstructive pulmonary disease or asthma, restrictive lung disease, or pulmonary hypertension) within 6 months prior to randomization or any history of interstitial lung disease (ILD) or pneumonitis requiring treatment with steroids (≥ Grade 2), or who have current or suspected ILD or pneumonitis.
9) Participants who are pregnant or breastfeeding.
10) Any other serious or uncontrolled medical disorder, active infection, physical examination finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a participant’s ability to comply with the study requirements, substantially increase the risk to the participant, or impact the interpretability of study results.
Please see protocol for full exclusion criteria
