Clinical Trial 24292

• Overview

  Study Title:

  A Phase 2a, Multi-Center, Open-Label Study to Compare Two Dosing Regimens of 177Lu-TLX250 (lutetium (177Lu) girentuximab tetraxetan) in Participants with Carbonic Anhydrase IX (CAIX) Expressing, Advanced Relapsed or Recurrent Clear Cell Renal Cell Carcinoma (ccRCC)

  Summary:

  Multicenter Phase 2A 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).

  Objective:

  Primary Objectives: -To select of the recommended Phase 3 dose (RP3D) from the two administered dose regimen. Secondary Objectives: - To evaluate pharmacokinetics (PK), biodistribution, and dosimetry data for 177Lu-TLX250 to support the determination of the recommended Phase 3 dose (RP3D) in a subgroup of participants. - To assess the objective response rate (ORR) for participants receiving 177Lu-TLX250 - To assess the duration of response (DoR) of participants receiving 177Lu-TLX250 - To assess the progression-free survival (PFS) for participants receiving 177Lu-TLX250 - To assess the disease control rate (DCR) of participants receiving 177Lu-TLX250 - To assess overall survival (OS) for participants receiving 177Lu-TLX250 - To evaluate Exposure-Response supporting dosing strategy - Evaluate the development of anti-drug antibodies (ADA) and their impact on the safety and efficacy of 177Lu-TLX250

• Treatments

  Therapies:

  Antibody-based positron emission tomography (PET) imaging modality used to non-invasively detect clear cell renal cell carcinoma (ccRCC); Targeted delivery of beta radiation to CAIX-expressing tumor cells via antibody

  Medications:

  177Lu-TLX250 (); 89Zr-TLX250 ()

• Inclusion Criteria

  Key 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.
  • Females of childbearing potential must have a negative serum pregnancy test during screening and prior to the dose of the IMP; must not be breast-feeding; and must agree to use a highly effective method of contraception (see Appendix 10.4) during treatment and for 6 months following last dose of the IMP.
  • Additional criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • 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, desferrioxamine (DFO) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) linker, zirconium or lutetium, and/or any excipient in the study drug or radiographic contrast-agents.
  • Has received granulocyte colony stimulating factor (G-CSF) or erythropoietin within 4 weeks prior to laboratory evaluations at Screening.
  • 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 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 individuals 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 individual's participation in a clinical study.
  • Additional criteria may apply.

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