Klinische Studien Radar

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Number of participants experiencing ≥1 treatment-emergent adverse event (TEAE) and ≥1 serious adverse event (SAE), graded per NCI CTCAE v5.0. Adverse events will be coded using MedDRA. Analyses will be performed in the safety population (all participants receiving ≥1 dose of study treatment).

From first dose through 30 days after last dose (SAEs and immune-related AEs followed for 90 days after last dose); survival/safety follow-up through 104 weeks (2 years) post last dose.

Clinically important changes in laboratory tests and vital signs

Number and percent of participants with protocol-defined clinically important laboratory abnormalities (hematology, chemistry including liver/renal, coagulation) or vital-sign changes that meet action criteria or result in dose modification, treatment interruption, or discontinuation; summarized by grade and action taken.

Baseline (pre-dose) through 30 days after last dose (clinically important labs/vitals and related actions); SAE/irAE follow-up 90 days; long-term follow-up through 104 weeks (2 years) post last dose.

RFS, defined as time from surgical resection to disease recurrence or death from any cause, whichever occurs first, by RECIST v1.1.

Recurrence-free survival (RFS) measured by RECIST v1.1: time (days) from surgical resection to first documented disease recurrence (radiographic per RECIST v1.1, confirmed per protocol) or death from any cause. Tumor assessments per protocol imaging schedule (every 8 weeks ±1 week) and iRECIST guidance for immune-related events; participants initiating new anticancer therapy or completing follow-up without recurrence are censored at last documented recurrence-free date. Report Kaplan-Meier curve, median RFS and 95% CI, and number (%) of events and censored observations.

From date of surgical resection until documented disease recurrence or death from any cause, whichever occurs first; participants censored at last disease assessment or at 104 weeks (2 years) post last dose.

R0 resection rate, defined as the percentage of cases having a pathologically complete resection with a negative resection margin.

Percentage of participants with a pathologically confirmed R0 resection (complete resection with negative margins). Report n and %, and exact 95% Clopper-Pearson CI.

At time of surgical resection (performed within 8 months of first study dose).

ORR by RECIST v1.1

Objective response rate (confirmed CR or PR per RECIST v1.1, confirmation ≥4 weeks after initial response). Report n and %, 2-sided exact 95% CI, and best overall response distribution.

From first study treatment until documented objective response or censoring; tumor assessments every 8 weeks (±1 week) through last treatment dose and per follow-up schedule through 104 weeks.

DOR by RECIST v1.1.

Duration of response for participants with confirmed CR/PR by RECIST v1.1. Analyze by Kaplan-Meier; present median DOR and 95% CI, KM curve, and numbers at risk.

For responders, from date of first documented CR/PR to date of documented progression or death (any cause); follow until event or censoring through 104 weeks.

Immune Recurrence-Free Survival (iRFS) by iRECIST

Immune recurrence-free survival (iRFS), defined as time from surgical resection to immune-confirmed recurrence (iCPD per iRECIST) or death from any cause, whichever occurs first. iRFS will be analyzed using Kaplan-Meier methods, with median iRFS and two-sided 95% confidence intervals summarized.

From date of surgical resection until immune-confirmed progression (iCPD), death, or censoring, with imaging every 8 weeks (±1 week) through 104 weeks after last dose.

Immune Objective Response Rate (iORR) by iRECIST

Immune objective response rate (iORR), defined as the proportion of participants with a confirmed immune complete response (iCR) or immune partial response (iPR) per iRECIST. Best overall immune response will be determined, and iORR with two-sided 95% confidence intervals will be summarized.

From first dose until immune-confirmed progression (iCPD), death, or censoring, with imaging every 8 weeks (±1 week) through 104 weeks after last dose.

Immune Duration of Response (iDOR) by iRECIST

Immune duration of response (iDOR), defined for participants with a confirmed iCR or iPR per iRECIST as the time from the first documented iCR/iPR to immune-confirmed progression (iCPD) or death from any cause, whichever occurs first. iDOR will be analyzed using Kaplan-Meier methods, with median iDOR and two-sided 95% confidence intervals summarized. Time Frame:

From first confirmed iCR or iPR until immune-confirmed progression (iCPD), death, or censoring, with imaging every 8 weeks (±1 week) through 104 weeks after last dose.

OS, defined as time from start of study treatment to death resulting from any cause.

Overall survival assessed by Kaplan-Meier. Present OS curve, median OS with 95% CI, number (%) of deaths, and survival rates at prespecified timepoints.

From date of first study treatment to death from any cause; participants censored at last known alive date; follow through 104 weeks (2 years) post last dose (or longer if protocol specifies).

Major pathologic response, defined as CAP TRG of 0 or 1 at the time of surgical resection.

Proportion of resected participants with major pathologic response defined as CAP Tumor Regression Grade 0 or 1 on surgical specimen. Report n and %, and exact 95% CI; provide distribution of CAP TRG scores.

At time of surgical resection (tissue collected at resection).

Biochemical response, defined as > 50% decrease in CA 19-9 from baseline

Proportion of participants achieving a biochemical response, defined as \>50% decrease in CA 19-9 from baseline. Report n and %, 95% CI, timing to response, and summary statistics (median percent change, time to nadir).

From baseline (pre-treatment) through the earliest of disease recurrence/progression, start of new anti-cancer therapy, or 104 weeks after last dose; CA 19-9 measured at baseline and on Day 1 of each 28-day treatment cycle.

Whole Slide Image Availability for Exploratory Image-Outcome Analyses

Number of participants with evaluable high-resolution whole slide images (H\&E-stained tumor tissue, digital or scanned slides) collected for exploratory analyses. Slides may undergo quantitative histomorphometry, immune/tumor microenvironment characterization, and AI/algorithmic feature extraction. Image-derived features will be analyzed in relation to clinical and pathologic outcomes (e.g., RFS, iRFS, ORR/iORR, DOR/iDOR, OS, CAP TRG) and biomarker data (ctDNA, CA 19-9) using prespecified statistical methods (e.g., multivariable models, supervised/unsupervised learning with adjustment for key covariates). For this Outcome Measure, the primary metric is the number of participants with at least one evaluable whole slide image available for such analyses.

From baseline diagnostic biopsy (screening) and/or surgical resection up to End-of-Treatment (EOT), assessed up to 104 weeks after first dose.

Blood for ctDNA analysis.

Number of participants with evaluable plasma specimens for circulating tumor DNA (ctDNA) analysis. Blood will be collected for tumor-informed and/or tumor-agnostic ctDNA assays to profile somatic alterations and quantify ctDNA levels. For this Outcome Measure, the primary metric is the number of participants with at least one evaluable ctDNA sample at any protocol-specified collection time point.

From baseline and Day 1 of neoadjuvant Cycles 3 and 5 (each cycle is 28 days), Day 1 of adjuvant Cycle 1 (28-day cycle), and Day 1 of every third adjuvant cycle thereafter, through End-of-Treatment (EOT), assessed up to 104 weeks after last dose.