A Study of Nuzefatide Pevedotin (BT5528) in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

A Phase 2 Study of BT5528 in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

This is a Phase 2 study for nuzefatide pevedotin (BT5528) in adults with a specific type of pancreatic cancer called metastatic pancreatic ductal adenocarcinoma (PDAC) that has spread and worsened after one previous treatment.

The drug, nuzefatide pevedotin (nuzefatide), is designed to find a specific protein called EphA2.

The main aims of the study are to see how well the drug works against the tumor (efficacy), what side effects it may have (safety), and how the body processes it (pharmacokinetics). All participants in this study will receive nuzefatide, and both they and their doctors will know what is being administered (single-arm, open-label). The trial will take place at several different medical centers.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma (PDAC)
• Intervention / Treatment: Drug: nuzefatide pevedotin (BT5528)

Detailed Description

This is a Phase 2, open-label, multicenter, single-arm study to evaluate the efficacy, safety, and pharmacokinetics (PK) of nuzefatide in adult participants with metastatic pancreatic ductal adenocarcinoma (PDAC) who have progressed on or after one prior line of systemic therapy. Nuzefatide is a novel Bicycle® drug conjugate (BDC®) that targets EphA2, a protein often found on cancer cells, and delivers a potent anti-cancer agent (MMAE).

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: BicycleTx Limited; Phone Number: 617-945-8155; Email: clinicalstudies@bicycletx.com

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University, Sidney Kimmel Comprensive Cancer Center, Clinical Trials Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• At least 18 years of age at the time of signature of the informed consent form
• Measurable disease as defined by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Histologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC)
• Participants must have failed only 1 prior line of therapy with evidence of radiographic progression. Neoadjuvant or adjuvant systemic therapy may count as the first line if the participant progressed less than 6 months from the end of systemic therapy. Prior treatment with KRAS inhibitors is permitted
• Participants must have sufficient tumor tissue (fresh or archived) available for analysis of EphA2 tumor expression and other biomarkers
• Adequate organ function (hematologic, renal, and hepatic)
• Negative pregnancy test for participants of childbearing potential (POCBP)
• Must be willing and able to comply with the protocol and study procedures

Exclusion Criteria

• Chemotherapy or radiotherapy within 14 days prior to the first dose of study treatment
• Experimental treatments within 28 days or 5 half-lives, whichever is longer, of first dose of nuzefatide study treatment
• Prior treatment with taxane therapy (e.g., paclitaxel) for pancreatic cancer or prior treatment with any MMAE-containing agent
• Known microsatellite instability-high (MSI-H) status and are eligible for immune checkpoint inhibitor therapy
• Prior toxicities must have resolved to Grade 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v6.0
• Untreated central nervous system (CNS) metastases

Note: Additional protocol defined Inclusion/Exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nuzefatide pevedotin (BT5528) Monotherapy	Drug: nuzefatide pevedotin (BT5528); Participants will receive nuzefatide pevedotin (BT5528) via intravenous (IV) infusion every 2 weeks (Q2W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DoR) per RECIST v1.1	The time from the first documentation of a tumor response (that is subsequently confirmed) to the first documentation of disease progression or death per RECIST v1.1	Up to approximately 3 years
Overall Survival (OS)	The length of time from the first day of study treatment (Day 1) to day of death	Up to approximately 3 years
Disease Control Rate (DCR) per RECIST v1.1	Percentage of participants who achieve a confirmed CR, PR, or stable disease (SD) per RECIST v1.1	Up to approximately 3 years
Clinical Benefit Rate (CBR) per RECIST v1.1	Defined as the proportion of participants with CR, PR, or SD ≥12 weeks per RECIST v1.1	Up to approximately 3 years
Progression-Free Survival (PFS) per RECIST v1.1	The time from the first day of study treatment to the first documentation of disease progression or death per RECIST v1.1	Up to approximately 3 years
Incidence of treatment-emergent adverse events (TEAEs)	Proportion of participants experiencing an adverse event on treatment	Up to approximately 3 years
Incidence of treatment emergent serious adverse events (TESAEs)	Proportion of participants experiencing serious adverse events on treatment	Up to approximately 3 years
Incidence of laboratory abnormalities	Proportion of participants that experience abnormal laboratory values (blood chemistry (including liver function tests and creatinine clearance), hematology (including hemoglobin, neutrophil and platelet absolute counts)) on treatment	Up to approximately 3 years
Incidence of ECG abnormalities	Proportion of participants that experience abnormal ECG parameters on treatment	Up to approximately 3 years
Incidence of abnormal vital signs	Proportion of participants that have changes in vital signs such as blood pressure, heart rate, oxygen saturation, respiratory rate, and body temperature on treatment	Up to approximately 3 years
Incidence of treatment modification due to adverse events	Proportion of participants that require any treatment modification due to adverse events	Up to approximately 3 years
Time to Progression (TTP) per RECIST v1.1	TTP defined as the time from first dose of nuzefatide until date of first documentation of disease progression per RECIST v1.1	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: BicycleTx Limited

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 5, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Metastatic; Pancreatic Ductal Adenocarcinoma; EphA2; PDAC; MMAE; BT5528; Bicycle Drug Conjugate; Nuzefatide Pevedotin
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Pancreatic Neoplasms
• Other Study ID Numbers: BT5528-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No