Phase 2/3 Randomized Study of Telisotuzumab Adizutecan Combined with FOLFOX versus Standard of Care in First‑Line Metastatic Pancreatic Ductal Adenocarcinoma

The study’s primary objectives are to (Phase 2) assess the safety and tolerability of telisotuzumab adizutecan in combination with FOLFOX, determine efficacy based on Objective Response per blinded independent central review, and identify the recommended Phase 3 dose; and (Phase 3) compare the efficacy of the same regimen versus standard of care using Objective Response and Overall Survival as endpoints. Secondary objectives include, for Phase 2, a detailed efficacy evaluation using Progression‑Free Survival, Duration of Response, and Clinical Benefit per central review together with overall survival, and the characterization of pharmacokinetics and immunogenicity of the investigational agent; for Phase 3, efficacy assessment with the same survival and response measures, safety and tolerability comparison with standard therapy, assessment of patient‑reported function and pancreatic cancer symptoms using the EORTC QLQ‑C30 (and QLQ‑PAN26), and evaluation of patient‑reported tolerability and treatment‑related adverse events employing the FACT GP5 and PRO‑CTCAE instruments.

The trial enrolled 706 participants diagnosed with metastatic pancreatic ductal adenocarcinoma. Both female and male patients were included, encompassing the age categories denoted by codes 3 and 4, and the population was classified as vulnerable. Eligibility required unresectable, histologically or cytologically confirmed disease, an ECOG performance status of 0 or 1, measurable lesions according to RECIST v1.1, and consent to provide archived or recent tumor tissue. Selection was based on these clinical criteria without additional specification of diet, physical activity, or other lifestyle factors.

The study is an open‑label, randomized, controlled Phase 2/3 trial evaluating intravenous telisotuzumab adizutecan in combination with fluorouracil, folinic acid, and oxaliplatin (FOLFOX) versus standard‑of‑care FOLFOX in adults with first‑line metastatic pancreatic ductal adenocarcinoma. Eligible participants are randomized in a 1:1 ratio after a screening visit that confirms unresectable metastatic disease, ECOG performance status 0‑1, and measurable disease per RECIST v1.1. Following randomization, a baseline visit initiates the assigned treatment regimen, which is administered intravenously on a regular schedule (e.g., every two weeks). Subsequent study visits occur at each treatment administration for safety monitoring, laboratory assessments, and drug dispensing, with radiographic tumor evaluations performed approximately every eight weeks to assess response. Participants remain on therapy until disease progression, unacceptable toxicity, withdrawal of consent, or a protocol‑specified maximum treatment duration, after which an end‑of‑study visit collects final efficacy and safety data. The overall participant involvement is expected to span up to 12 months of treatment and follow‑up, with continued survival follow‑up for overall survival assessment. Early termination of a participant’s participation may occur if disease progression is documented, if grade ≥ 3 treatment‑related adverse events are not resolved, if protocol non‑compliance is identified, or if the participant elects to discontinue. The primary efficacy endpoints are Objective response assessed by blinded independent central review per RECIST v1.1 and overall survival, with secondary endpoints including progression‑free survival, duration of response, clinical benefit, and various patient‑reported outcome measures.

Telisotuzumab adizutecan is the investigational monoclonal antibody administered as a solution for infusion for intravenous delivery. The dose is specified in milligrams per square meter of body‑surface area and is given according to the study‑defined treatment cycle, typically once per cycle on the day of infusion. Administration is performed under controlled infusion conditions with monitoring of vital signs and infusion‑related reactions.

Calcium folinate (leucovorin) is supplied as the pharmaceutical form PHF00231MIG and is administered intravenously. The dose is expressed in milligrams and follows the protocol‑specified amount for each treatment cycle. It is given as an infusion preceding or concurrent with fluorouracil as part of the FOLFOX regimen.

Oxaliplatin, provided in the PHF00230MIG formulation, is delivered by intravenous infusion. The protocol‑defined milligram dose is administered on the first day of each treatment cycle, in accordance with standard FOLFOX dosing schedules.

Fluorouracil, also supplied as PHF00231MIG, is given intravenously. The study specifies a milligram dose that is infused continuously or as a bolus on the day of oxaliplatin administration, consistent with the FOLFOX protocol.

Irinotecan hydrochloride, presented in the PHF00230MIG form, is administered intravenously at a protocol‑determined milligram dose. It is infused on the designated day of the treatment cycle according to the comparator arm schedule.

All study medications are administered in a clinical setting with dosing cycles defined by the protocol (typically every two weeks). Compliance is monitored through infusion records, dose‑modification logs, and regular assessment of laboratory and clinical parameters to ensure adherence to the prescribed regimen and to manage any adverse events.

Efficacy will be evaluated primarily by Objective response (OR) assessed through a Blinded Independent Central Review (BICR) according to RECIST v1.1, and by Overall Survival. These endpoints will be compared between the investigational regimen and the standard of care.

Secondary efficacy assessments include Progression-Free Survival, Duration Of Response, and Clinical Benefit, all determined by BICR using RECIST v1.1 criteria. Patient‑reported outcome measures comprise changes from baseline and time to deterioration on the EORTC QLQ-C30 and EORTC QLQ-PAN26 instruments, as well as selected items from the PRO-CTCAE, the FACT-G GP5 item, and the PGIS/PGIC scales. Health‑related quality of life will be further evaluated by change from baseline in the EQ-5D-5L utility index and visual analog scale.