Status and phase
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About
Multicenter Phase 3 study of 177Lu-TLX250 in adult participants with CAIX-expressing advanced, relapsed or recurrent clear cell renal cell carcinoma (ccRCC). Part 1 will evaluate two dosing regimens to determine the recommended Phase 3 dose (RP3D). Part 2 will compare 177Lu-TLX250 with investigator's choice of monotherapy aligned with Australian standard-of-care.
Full description
This is a randomized, open-label, multi-center 3 study evaluating the safety and efficacy of 177Lu-TLX250, a CAIX-targeting radioligand therapy, in adult participants with advanced, relapsed or recurrent clear cell renal cell carcinoma (ccRCC).
The study consists of two parts:
• Part 1 (Phase 2a - Dose Optimization): Participants will be randomized to receive one of two dosing regimens of 177Lu-TLX250.
The objective of Part 1 is to determine the recommended Phase 3 dose (RP3D) for use in Part 2.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
be aged ≥ 18 years.
have provided written informed consent, dated and signed by the participant prior to any study-specific procedure;
have relapsed or recurrent, locally advanced, or metastatic RCC with histologically or cytologically confirmed diagnosis of RCC with clear cell component per American Joint Committee on Cancer Staging Manual (Edge SB et al., 2017), with or without sarcomatoid features;
have received at least 2 and no more than 3 prior lines of systemic therapies for locally advanced or metastatic ccRCC including a PD-1/PD-L1 inhibitor (at least 2 administrations) and a VEGF/VEGFR-targeting agent (including TKI or mAb) in sequence or in combination;
have had radiographic disease progression occurring during or after the most recent line of therapy or intolerance to most recent line of therapy;
have at least one measurable lesion according to RECIST, version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions;
be CAIX-positive at Screening defined as having at least 1 lesion with a tumor-lesion CAIX ratio of the maximum standardized uptake value (SUVmax) to liver mean standardized uptake value SUVmean) ≥ 1.5 as determined by BICR of 89Zr-TLX250 PET outcomes;
have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1;
have recovered from the AEs related to prior lines of therapy or returned to baseline with the exception of Grade 2 neurotoxicity. Ongoing, controlled AEs, such as hypothyroidism or hypertension, are permitted;
have adequate organ function, defined as:
Bone Marrow:
Liver Function:
Renal Function:
Exclusion criteria
have any of the following:
received prior 177Lu-TLX250 therapy, any other radioligand therapy, or any prior CAIX-targeting therapy;
have any known hypersensitivity to compounds of similar chemical or biologic composition to girentuximab, DFO or DOTA linker, zirconium or lutetium, and/or any excipient in the study drug or radiographic contrast-agents;
has received G-CSF or erythropoietin within 4 weeks prior to laboratory evaluations at Screening;
be currently receiving or have received:
have known brain metastases, unless these have been treated and stabilized for at least 4 weeks prior to the first administration of 177Lu-TLX250; Note: Participants with a history of brain metastases must have either a head CT with contrast-or brain MRI performed at Screening to document stable disease prior to the first administration of 177LuTLX250.
Have experienced any major trauma including major surgery (such as abdominal/ cardiac/thoracic surgery) within 3 weeks of administration of the first administration of 177LuTLX250;
be pregnant or intend to become pregnant, breastfeed, or conceive a child during the study period and for at least 42 days after last administration of 89Zr-TLX250 or 6 months after last administration of 177Lu-TLX250, depending on which study drug is administered last to the respective participant;
Note: Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see Appendix 10.4).
be planning to breastfeed during the study period and for 28 days after last administration of 89ZrTLX250 or 75 days after last administration of 177Lu-TLX250, depending on which study drug is administered last to the respective participant;
have active and uncontrolled infections requiring systemic therapy or other severe concurrent disease, which, in the opinion of the investigator, would place the participant at undue risk or interfere with the study;
have a history of concurrent malignancy with a life expectancy of ≤ 2 years or requirement of systemic anti-cancer therapy or requirement of local therapy that would confound study results; however; participants with the following malignancies can be enrolled into the study:
have a serious, non-healing wound, ulcer, or bone fracture;
be unable to stay in the scanner bed with the arms resting out of the thoracic and abdominal fields (i.e., arms alongside the body or raised arm position) for the duration of the scan;
have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 (except for laboratory parameters specified above, Grade 2 alopecia, and/or stable Grade 2 sensory neuropathy, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0;
have inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis, etc.);
have a life expectancy shorter than 3 months;
have bleeding or thrombotic disorders or subjects at risk for severe hemorrhage;
have experienced any clinically significant bleeding, including hemoptysis or tumor bleeding within 2 weeks prior to the first administration of 177Lu-TLX250;
has evidence of a serious active or sub-clinical infection or angina pectoris (New York Heart Association [NYHA] Class III or IV), significantly prolonged QT interval or other serious illness(es) involving the cardiac, respiratory, central nervous system, renal, hepatic or hematological organ systems, that might impair the ability to complete this study or could interfere with determination of causality of any adverse effects experienced in this study, or which require treatment that could interact with study treatment; or
have any medical or other condition that in the opinion of the investigator(s) would preclude the subject's participation in a clinical study.
Primary purpose
Allocation
Interventional model
Masking
40 participants in 2 patient groups
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Central trial contact
Prson Gautam, PhD; Lily Nahidi, PhD
Data sourced from clinicaltrials.gov
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