This is an open-label, nonrandomized, multicenter study conducted in two sequential parts: an initial Phase 2 Dose Optimization Period followed by the Phase 3 Diagnostic Performance Period. After the optimal administered activity and imaging time window are selected in Phase 2, Phase 3 will enroll participants with recently diagnosed PCa who are at least high risk or have suspected metastatic disease and are eligible for radical prostatectomy with pelvic lymph node dissection (RP+PLND). Safety assessments throughout the study will include monitoring of adverse events, vital signs, ECGs, and clinical laboratory parameters. Participants will be enrolled sequentially in a nonrandomized manner, with competitive enrollment across study sites.
Phase 2 Dose Optimization Period During the Phase 2 period, participants will receive 5 (±1) mCi (148 to 222 MBq) of \[68Ga\]-LNTH-2401 for PET/CT imaging with the primary objectives of determining the optimal administered activity, imaging parameters and tissue dosimetry. Up to 12 participants with GRPR-positive lesion(s) will undergo serial PET/CT scans at multiple time points during the first imaging visit to assess dosimetry and biodistribution. Data from 6 eligible participants with GRPR-positive lesion(s) will be used to determine the optimal administered activity and imaging time window for Phase 3, with the possibility of enrolling additional participants if warranted. Dosimetry will be estimated from imaging data collected during the dose optimization period and analyzed using standard, validated methodologies appropriate for PET radiopharmaceuticals. Dosimetry calculations will be performed using Organ Level Internal Dose Assessment (OLINDA). Image quality evaluation will include qualitative assessment by qualified image readers and quantitative assessment of tumor-to-background characteristics for lesions identified on PET/CT. Lesion(s) demonstrating uptake consistent with GRPR expression may be evaluated to support assessment of lesion conspicuity, contrast, and interpretability across evaluated imaging parameters. These exploratory evaluations will be used solely to support selection of the optimized administered activity and imaging time window. Phase 2 dosimetry, biodistribution, and image quality assessment data will not contribute to the Phase 3 primary diagnostic performance analyses. Phase 3 Diagnostic Performance Period The Phase 3 Diagnostic Performance Period is designed to evaluate the diagnostic accuracy of\[68Ga\]-LNTH-2401 PET/CT for detecting prostate cancer in pelvic lymph nodes (primary; compared to histopathology) and in other anatomic regions, as defined by study endpoints. All Phase 3 participants will undergo \[68Ga\]-LNTH-2401 PET/CT imaging using the optimized administered activity and imaging time window selected in Phase 2. Diagnostic accuracy will be assessed using local histopathological evaluation of surgically removed pelvic lymph nodes, or other anatomic regions (as applicable) as the primary standard of truth (SOT). The primary diagnostic performance endpoints are participant-level sensitivity and participant-level specificity of \[68Ga\]-LNTH-2401 PET/CT for detection of prostate cancer in pelvic lymph nodes, derived from pelvic lymph node region-level classifications compared with region-matched histopathology. Secondary diagnostic performance assessments will use a composite standard of truth (CSOT) incorporating histopathology and, where applicable, anatomic correlation with conventional imaging modalities and/or PSMA PET imaging. All imaging data will be reviewed by 3 blinded central readers, and the CSOT will be established by an Independent Committee in accordance with a predefined charter. Additionally, safety and tolerability will be evaluated following administration of \[⁶⁸Ga\]-LNTH-2401 using the Phase 2-selected imaging parameters. Regional detection performance across anatomic sites and assessment of the impact of \[68Ga\]-LNTH-2401 PET/CT imaging on intended clinical management will also be explored in the Phase 3 portion of the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
408
\[68Ga\]-LNTH-2401 will be administered to identify newly diagnosed prostate cancer.
BAMF Health
Grand Rapids, Michigan, United States
RECRUITINGPhase 2 Dose Optimization Period: Optimal administered activity (radioactivity) and imaging time window for [68Ga]-LNTH-2401 PET/CT based on image quality and interpretability in participants with either newly diagnosed or BCR PCa
Image quality scores (IQS) for administered activity (radioactivity) for \[68Ga\]-LNTH-2401 PET/CT
Time frame: Day 1
Phase 2 Dose Optimization Period : Optimal administered activity (radioactivity) and imaging time window for [68Ga]-LNTH-2401 PET/CT based on image quality and interpretability in participants with either newly diagnosed or BCR PCa
Image quality scores (IQS) for imaging time windows for \[68Ga\]-LNTH-2401 PET/CT
Time frame: Day 1
Phase 2 Dose Optimization Period :Biodistribution and radiation dosimetry of [68Ga]-LNTH-2401 in participants with either newly diagnosed or BCR PCa.
Time activity curves (TACs), describing the percentage of the injected activity versus time will be derived for standard organs. Absorbed radiation doses of \[68Ga\]-LNTH-2401in standard organs; whole-body effective dose will also be estimated.
Time frame: Day 1
Safety and tolerability of [68Ga] LNTH 2401 in participants with either newly diagnosed or BCR PCa.
Frequency and severity of AEs per CTCAE version 6.0 for \[68Ga\]-LNTH-2401.
Time frame: 1 week (Ph2), 6 months (Ph3)
Safety and tolerability of [68Ga] LNTH 2401 in participants with either newly diagnosed or BCR PCa.
Clinical laboratory parameters (e.g., hematology, chemistry), vital signs, and ECG parameters after administration of \[68Ga\]-LNTH 2401.
Time frame: 1 week (Ph2), 6 months (Ph3)
Phase 3 Diagnostic Performance Period- Diagnostic accuracy (sensitivity and specificity) of [68Ga]-LNTH-2401 PET/CT imaging for detecting prostate cancer in pelvic lymph nodes, compared to histopathology.
Co-primary endpoints of: Participant-level specificity (TN/\[TN + FP\]) of \[68Ga\]-LNTH-2401 PET/CT for detection of prostate cancer in pelvic lymph nodes relative to histopathology. Participant-level sensitivity (TP/\[TP + FN\]) of \[68Ga\]-LNTH-2401 PET/CT for detection of prostate cancer in pelvic lymph nodes relative to histopathology.
Time frame: Enrollment through study completion, average 6 months
Phase 2 Dose Optimization Period- Refine the GRPR positivity definition
Prior and newly collected radioactivity uptake data (e.g., SUVmean, SUVmax ranges)
Time frame: Day 1
Phase 3 Diagnostic Performance Period- Evaluation of the safety and tolerability of [68Ga]-LNTH-2401.
Frequency and severity of AEs per CTCAE version 6.0 for \[68Ga\]-LNTH-2401. Changes in clinical laboratory parameters (e.g., hematology, chemistry), vital signs, and ECG parameters after administration of \[68Ga\]-LNTH 2401.
Time frame: From Enrollment to End of treatment of Ph3
Phase 3 Diagnostic Performance Period- Determination of (true) detection rates of [68Ga]-LNTH-2401 and conventional imaging (CT/MRI of pelvis, ultrasound, bone scan) or PSMA PET/CT or PET/MRI among anatomic regions
The true detection and detection rates of \[68Ga\]-LNTH-2401 PET/CT among regions (e.g., bone, pelvic lymph nodes, extra-pelvic lymph nodes, soft tissue, prostate gland) between \[68Ga\]-LNTH-2401 and conventional (CT/ MRI of pelvis, ultrasound, bone scan) and/or PSMA PET imaging. Comparison of detection rates between PSMA and GRPR imaging, based on pre-specified analysis.
Time frame: From Enrollment to End of treatment of Ph3
Phase 3 Diagnostic Performance Period- Assessment of the diagnostic performance of [68Ga]-LNTH-2401 PET/CT imaging of prostate cancer within the prostatic region.
Specificity (TN/ \[TN + FP\]) of \[68Ga\] LNTH-2401 PET/CT imaging to determine the absence of prostate cancer within prostatic region relative to histopathology. Sensitivity (TP/ \[TP + FN)\] of \[68Ga\]-LNTH-2401 PET/CT imaging a to determine the presence of prostate cancer within prostate relative to histopathology.
Time frame: From Enrollment to End of treatment of Ph3
Phase 3 Diagnostic Performance Period- To determine the patient level and region level diagnostic performance of [68Ga] LNTH-2401 PET/CT imaging prostate cancer within the pelvic lymph nodes or other metastatic lesions.
PPV and NPV of \[68Ga\]-LNTH-2401 PET/CT imaging for prostate cancer relative to the composite SOT.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: From Enrollment to End of treatment of Ph3
Phase 3 Diagnostic Performance Period- To assess the impact of [68Ga]-LNTH-2401 PET/CT imaging on intended clinical management plans.
Proportion of participants with any change in intended clinical management plan from pre-dose to post-dose \[68Ga\]-LNTH-2401 PET/CT, based on a review of clinical and radiographic participant data, and captured by the treating physician using a structured Medical Management Questionnaire (MMQ).
Time frame: From Enrollment to 6 months follow-up