Pancreatic Ductal Adenocarcinoma (PDAC)
Conditions
Keywords
Pancreatic Cancer, BT5528, EphA2, Bicycle Drug Conjugate, MMAE, Metastatic, Pancreatic Ductal Adenocarcinoma, PDAC, Nuzefatide Pevedotin
Brief summary
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 or two prior lines of treatment if treated with KRAS inhibitor. 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.
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) whose disease has progressed on or after one prior line of systemic therapy in the metastatic setting or on or after second line therapy with a KRAS inhibitor in the metastatic setting. 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).
Interventions
DRUGnuzefatide pevedotin (BT5528)
Participants will receive nuzefatide pevedotin (BT5528) via intravenous (IV) infusion every 2 weeks (Q2W)
Sponsors
BicycleTx Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age at the time of signature of the informed consent form (or at least 19 years where locally defined as minimum age of consent). * 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 whose disease has progressed on or after only 1 prior line of therapy or on or after second line therapy with a KRAS inhibitor, 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 in the first-line setting is permitted if there was no intervening treatment prior to enrollment. * 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 and agree to participate in the study by providing written informed consent.
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 3 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) per RECIST v1.1 | Up to approximately 3 years | 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 |
| Overall Survival (OS) | Up to approximately 3 years | The length of time from the first day of study treatment (Day 1) to day of death |
| Disease Control Rate (DCR) per RECIST v1.1 | Up to approximately 3 years | Percentage of participants who achieve a confirmed CR, PR, or stable disease (SD) per RECIST v1.1 |
| Clinical Benefit Rate (CBR) per RECIST v1.1 | Up to approximately 3 years | Defined as the proportion of participants with confirmed CR, PR, or SD ≥12 weeks per RECIST v1.1 |
| Progression-Free Survival (PFS) per RECIST v1.1 | Up to approximately 3 years | The time from the first day of study treatment to the first documentation of disease progression or death per RECIST v1.1 |
| Time to Progression (TTP) per RECIST v1.1 | Up to approximately 3 years | TTP defined as the time from first dose of nuzefatide until date of first documentation of disease progression per RECIST v1.1 |
| Incidence of treatment-emergent adverse events (TEAEs) | Up to approximately 3 years | Proportion of participants experiencing an adverse event on treatment |
| Incidence of treatment-related adverse events (TRAEs) | Up to approximately 3 years | Proportion of participants experiencing an adverse event determined by the Investigator to be related to study treatment |
| Incidence of treatment emergent serious adverse events (TESAEs) | Up to approximately 3 years | Proportion of participants experiencing serious adverse events on treatment |
| Incidence of laboratory abnormalities | Up to approximately 3 years | 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 |
| Incidence of ECG abnormalities | Up to approximately 3 years | Proportion of participants that experience abnormal ECG parameters on treatment |
| Incidence of abnormal vital signs | Up to approximately 3 years | Proportion of participants that have changes in vital signs such as blood pressure, heart rate, oxygen saturation, respiratory rate, and body temperature on treatment |
| Incidence of treatment modification due to adverse events | Up to approximately 3 years | Proportion of participants that require any treatment modification due to adverse events |
Countries
South Korea, United States
Contacts
CONTACTBicycleTx Limited
Outcome results
None listed