PRL3-Zumab in Patients With Advanced Solid Tumors
brief summary
This is a multicenter, Phase II, open-label, single-dose-level (6 mg/kg) study of PRL3-zumab monotherapy in patients with unresectable or metastatic solid tumors. PRL3-zumab will be administered via intravenous (IV) infusion until discontinuation criteria are met (e.g., disease progression per RECIST v1.1/iRECIST, intolerable toxicity, or withdrawal of consent). Study Periods and Duration The study is divided into the following phases: * Screening Period: Day -21 to Day -1; all assessments must be completed prior to the first dose. * Treatment Period: One cycle is defined as 4 weeks, consisting of two infusions administered 2 weeks apart. * End-of-Treatment (EOT) Visit: To be conducted within 14 days of the last dose or treatment discontinuation. * Safety Follow-Up: A visit scheduled 30 days after the last dose. * Survival Follow-Up: Conducted every 3 months post-discontinuation via telephone or other appropriate methods until the data cutoff date. Assessments * Safety \& QoL: Safety assessments (including laboratory tests) will be performed prior to each infusion. Quality of Life (QoL) will be assessed at screening and every 8 weeks during treatment. * Tumor Imaging: Assessments will be performed at baseline and every 8 weeks following the initiation of study treatment, according to RECIST v1.1 and iRECIST. * Immunogenicity: Assessments will be performed pre-dose on Cycle 1 Day 1, and prior to infusions in Cycles 2, 4, and 6. For patients remaining on treatment, assessments will continue every 3 cycles thereafter. Pharmacokinetic (PK) profiles will be evaluated in two distinct subgroups of 10 patients each. For the intensive PK sampling subgroup, assessments are concentrated in the first three cycles: Cycle 1 monitoring includes Day 1 (pre-dose, end of infusion, 2, and 6 hours post-infusion), Day 2 (24 hours), Day 6 (120 hours), Day 10 (216 hours), and Day 15 (pre-dose). Following pre-dose samples on Cycle 2 (Days 1 and 15) and Cycle 3 (Day 1), a second intensive window occurs on Cycle 3 Day 15 (pre-dose, end of infusion, 2, and 6 hours post-infusion) and continues through Days 16, 20, and 24. Subsequent samples are taken pre-dose on Day 1 of Cycles 4, 5, and 6, concluding at the EOT visit. In contrast, the sparse PK sampling subgroup will undergo limited assessments at Cycle 1 Day 1 (pre-dose and end of infusion), Cycle 1 Day 15 (pre-dose), and the first day of Cycles 2 and 3 (pre-dose and end of infusion), with a final sample collected at the EOT visit.
detailed description
Study Assessments
Efficacy:
Efficacy will be evaluated by the investigator using RECIST v1.1 and iRECIST criteria. Tumor evaluations, including contrast-enhanced computed tomography (CT) scans, will be performed at baseline (within 14 days prior to Cycle 1 Day 1) and every 56 days thereafter. Magnetic resonance imaging (MRI) may be used if a patient is ineligible for CT scans; however, the same imaging modality must be used consistently throughout the study.
Safety:
Patient safety will be assessed on an ongoing basis during each cycle. Evaluations include physical examinations, vital signs (systolic/diastolic blood pressure, heart rate, respiratory rate, and temperature), and clinical laboratory tests (hematology, clinical chemistry, and coagulation). Adverse events (AEs) will be graded according to CTCAE v5.0.
Pharmacokinetics (PK):
Blood samples for PK analysis will be collected as follows:
* Intensive Sampling Group (N=10): C1D1 (pre-dose, EOI, 2h, and 6h post-infusion), C1D2 (24h), C1D6 (120h), C1D10 (216h), C1D15 (pre-dose); C2D1 and C2D15 (pre-dose); C3D1 (pre-dose), C3D15 (pre-dose, EOI, 2h, and 6h post-infusion), C3D16 (24h), C3D20 (120h), C3D24 (216h); C4D1, C5D1, C6D1 (pre-dose), and at End of Treatment (EOT). * Sparse Sampling Group: C1D1 (pre-dose, EOI), C1D15 (pre-dose); C2D1 and C3D1 (pre-dose and EOI), and at EOT.
Immunogenicity \& Quality of Life (QoL) Anti-drug antibody (ADA) samples will be collected prior to infusion on C1D1 and Cycles 2, 4, and 6. Thereafter, samples will be collected every three months. Neutralizing antibody assessments will be performed for any patient testing positive for ADA.
Quality of Life (QoL) will be measured using EQ-5D and EORTC-QLQ-C30 questionnaires at screening and every 2 cycles (8 weeks ± 2 days for C1-C4; 8 weeks ± 7 days thereafter).
Study Duration and Periods
* Cycle Period: One cycle is 28 days (two infusions administered 2 weeks apart). * Treatment Period: Treatment continues until disease progression (per RECIST 1.1/iRECIST or clinical criteria), intolerable toxicity, or withdrawal of consent. * Follow-up Period: Includes a Safety Follow-up (30 ± 7 days after the last dose or prior to new therapy) and a Survival Follow-up (every 3 months via telephone until the data cutoff date, which is 24 weeks after the last subject's enrollment).
official title
An Open Label, Multicenter, Safety and Efficacy Phase II Study of PRL3-Zumab in Solid Tumors