Trial Outcomes & Findings for XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer (NCT NCT04825288)

XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer

The primary objective of the Phase I portion is to identify the MTD of XB2001 when administered in combination with ONIVYDE + LV + 5-FU. The MTD is defined as the highest dose level at which no more than one out of six subjects experience a DLT. If two or more subjects in a cohort of six experience a DLT, the MTD is considered exceeded, and the previous lower dose level will be identified as the MTD. If no DLTs are observed at the highest dose level studied, that dose will be used for Phase II. A DLT is defined as any Grade 3-4 adverse event (per NCI CTCAE v5.0) occurring within the first 28 days that is deemed possibly related to the combination regimen, unless the toxicity is clearly attributable to a single non-XB2001 component. Specific DLT criteria include: 1. Inability to deliver all scheduled doses during the 28-day window due to unexpected drug-related toxicity. 2. Inability to deliver the intended dose of XB2001 due to drug-related toxicity.

This endpoint evaluates the cumulative safety profile and patient tolerance of XB2001 when administered at the Maximum Tolerated Dose (MTD) or the maximum dose studied in Phase I, in combination with the ONIVYDE + LV + 5-FU regimen. Safety is characterized by the total number of participants in each cohort who experienced one or more adverse events. For the purpose of this count, each participant is counted only once, regardless of the total number of individual adverse events experienced.

Progression free survival (PFS) was defined as the time from randomization to first progression based on RECIST v1.1 criteria or death from any cause, whichever occurred first. Subjects who had no baseline and post-baseline tumor assessment and no death, or no adequate post-baseline tumor assessment and no death were censored at the date of randomization. Subjects alive and without documented disease progression at the time of data analysis are censored at the date of the last adequate tumor assessment.

OS was defined as the duration from the date of randomization until death irrespective of the cause. Subjects who were alive at the time of analysis were censored at the last known date alive. Subjects without any data after baseline were censored on the randomization day.

Objective Response Rate (ORR) is defined as the proportion of subjects in the Phase II Population who achieved a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR), as defined by RECIST v1.1 criteria.

TTF measures the time from randomization to discontinuation of treatment for any reason, including, but not limited to, disease progression, treatment-related toxicity, and/or death during study.

This outcome measure calculates the total number of unique participants who reported serious adverse events (SAEs) in each group. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

This measure tracks the overall burden of severe (Grade 3) or life-threatening (Grade 4) diarrhea as defined by the NCI CTCAE v5.0. Grade 3 events are severe enough to require medical intervention or significantly limit a person's ability to care for themselves, while Grade 4 events represent urgent, life-threatening clinical situations.

This outcome measure calculates the sum of duration of hospitalizations during the study period in phase II population for both groups.

Measurement of the concentration of Natrunix in plasma samples to evaluate the pharmacokinetic profile. Due to reporting limitations on this portal, results from only one time point are reported here. For Phase 1, samples were collected at V1 pre-dose, V1 post-dose, V2 pre-dose, V3 follow up. For phase 2, samples were collected at V1 pre-dose, V1 post-dose, V1 Day 4, V1 Day 7, V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, and V13 follow up. Placebo patients were tested at V1 post-dose only for verification.

This measures the total number of cycles (total number of doses) received by subjects after randomization in each arm.

This outcome measure evaluates the number of participants who experienced stable or improved symptoms during treatment, specifically focusing on the core domains of Anorexia (Appetite Loss), Fatigue, and Pain. Quality of Life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30 version 3.0), a validated 30-item survey. To be classified as a "QoL Symptom Responder," a participant must demonstrate stabilization or improvement (no increase in symptom score) from their baseline in at least two of the three key areas (Anorexia, Fatigue, and Pain). Any increase in these scores indicates a worsening of symptoms.

This measure assesses the pharmacodynamic signal of absolute mean change in circulating Vascular Endothelial Growth Factor (VEGF) concentrations from baseline (Visit 1 pre-dose) at various time points (V1 day 4, V1 Day 7, V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, V13 follow-up visit). A negative value indicate a significant decrease of circulating VEGF from baseline. Due to reporting limitations, results from one representative time point are reported here.

This measure assesses the pharmacodynamic signal of absolute mean change in circulating Platelet-Derived Growth Factor (PDGF) concentrations from baseline (Visit 1 pre-dose) at various time points (V1 day 4, V1 Day 7), V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, V13 follow-up visit). A negative value indicate a significant decrease of circulating PDGF from baseline. Due to reporting limitations, results from one representative time point are reported here.

This measure assesses the pharmacodynamic signal of absolute mean change in Human Epidermal Growth Factor Receptor 2 (ERBB2/HER2) concentrations from baseline (Visit 1 pre-dose) at various time points (V1 day 4, V1 Day 7), V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, V13 follow-up visit).

This measure assesses the pharmacodynamic signal of absolute mean change in Epidermal Growth Factor (EGF) concentrations from baseline (Visit 1 pre-dose) at various time points (V1 Day 4, V1 Day 7), V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, V13 follow-up visit). A negative value indicates a decrease of circulating EGF from baseline.

This measure assesses the duration from randomization to the first occurrence of a "severe" or "life-threatening" adverse event (defined as CTCAE Grade 3 or higher).

This measure evaluates the number of subjects categorized as having Stable Disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. The assessment compares the clinical benefit between the Natrunix and placebo arms to determine improved tumor stability.

This measure evaluates the number of subjects categorized as having Disease Progression (PD) based on the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. The assessment compares the clinical benefit between the Natrunix and placebo arms to determine improved tumor stability.

Disease Control Rate (DCR) was calculated to evaluate the outcome of Natrunix therapy. It measures the proportion of subjects achieving an objective response or stable disease. DCR is calculated as the sum of subjects with a Complete Response (CR), Partial Response (PR), or Stable Disease (SD), compared to those with Progressive Disease (PD). This endpoint is used to assess the anti-tumor effects of Natrunix therapy in subjects with pancreatic cancer.

This outcome measure estimates the probability of hospitalization at the 24-week time point. A lower percentage indicates a lower probability of hospitalization and a favorable treatment effect.

The outcome measure calculates the interval from the date of randomization to the earliest occurrence of objective radiological progression, clinical progression, or death from any cause.

The interval from the date of randomization to the date of permanent discontinuation from the study for any reason.

This measure evaluates the change in cancer-related pain from baseline to visit 13 (Week 24), using the patient-reported EORTC QLQ-C30 questionnaire. Scores range from 0 to 100; higher scores represent more pain. A decrease in score signifies clinical improvement. The results shown below is the final mean score of each arm.

This measure evaluates the change in anorexia (loss of appetite) from baseline to visit 13 (Week 24), using the patient-reported EORTC QLQ-C30 questionnaire. Score ranges from 0 to 100. A decrease in score signifies clinical improvement. The results shown below is the final mean score of each arm.

This measure evaluates the change in fatigue from baseline to visit 13 (Week 24), using the patient-reported EORTC QLQ-C30 questionnaire. Score ranges from 0 to 100. A decrease in score signifies clinical improvement. The results shown below is the final mean score of each arm.

This measure evaluates the occurrence of TEAE fatigue, including both serious and non-serious, during the study period.

TEADA was evaluated by testing available samples at various time points (V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, V13 follow up) and comparing with baseline (V1 pre-dose). If baseline-corrected value at any time point is higher than assay lower limit of quantitation (LLOQ), the participant will count as having significant TEADA. Participants in the Phase II Placebo Arm were not exposed to Natrunix, and therefore, no data were collected from participants in the Phase II Placebo Arm for this Outcome Measure. All participants in Natrunix 1000 mg arm were analyzed but none of them developed TEADA.