Borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC) Cancer
Conditions
Interventions
Sotevtamab (800 mg IV infusion), gemcitabine (1,000 mg/m2 IV infusion), nab-paclitaxel (125 mg/m2 IV infusion), NAI (1.2 mg SC injection), and zabadinostat (10 mg BID PO for 5 days) will be the interv
Sponsors
Serum Life Science Europe GmbH
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Age =18 years old. 2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 4. Histologically or cytologically confirmed PDAC that is confined to the pancreas. 5. Borderline resectable (surgical resection possible but challenging) or locally advanced (surgical resection not possible) PDAC, as determined by the local investigator based on local institutional guidelines. 6. Measurable tumor lesions according to RECIST v1.1 (within 90 days prior to first dose of study treatment). 7. Have not received prior anticancer therapy for pancreatic cancer. 8. Ability to attend required study visits and return for adequate follow-up, as required by this protocol. 9. Agreement to practice effective contraception for female participants of child-bearing potential and non-sterile males. Female participants of child-bearing potential must agree to use effective contraception for up to 7 months after completion of therapy, and nonsterile male participants must agree to use a condom for up to 7 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), orals, injectables, two forms of barrier methods (e.g., condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and hormonal therapy.
Exclusion criteria
Exclusion criteria: 1. Resectable PDAC, meeting the following criteria upon CT/MRI: 1.1. No superior mesenteric vein (SMV) or portal vein (PV) distortion; and 1.2. Clear fat planes around superior mesenteric artery (SMA), celiac artery (CA), and common hepatic artery (CHA). 2. Participants for whom an operation is not considered in the participant’s best interest (eg, due to comorbidity). 3. Histologically or cytologically confirmed pancreatic tumor that is not adenocarcinoma. 4. CA19-9 > 1,000 U/mL. 5. QTc interval using Fridericia's formula (QTcF) > 470 ms. 6. If participants have had major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 7. Have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed. 8. Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 9. Inadequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to baseline: 9.1. Absolute neutrophil count (ANC) 2.5 × ULN, with the following exception: Participants with documented liver metastases: AST and/or ALT > 5 × ULN. 9.7. Serum bilirubin = 3 × ULN 9.8. Creatinine clearance = 60 mL/min (calculated using the Cockcroft-Gault formula). 9.9. Serum albumin = 3.0 g/dL. 9.10. Urine dipstick for proteinuria > 2+ (within 7 days prior to initiation of study treatment). Participants with = 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours. 10. Significant cardiovascular disease (such as New York Heart Association cardiac disease class II or greater), myocardial infarction within 3 months prior to baseline, unstable arrhythmias, or unstable angina. 11. Severe infections at the time of enrollment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. 12. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study. 13. Prior allogeneic bone marrow transplantation or solid organ transplant. 14. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that co
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Adverse events (AEs) and serious AEs (SAEs) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Safety is assessed from first study treatment through the End-of-Treatment (EOT) visit at 30 (+7) days post-last dose. AEs/SAEs are collected at every visit during neoadjuvant and adjuvant treatment. Non-serious AEs are followed for 30 days post-last dose; SAEs are followed until resolution/stabilisation. 2. Clinically significant changes in laboratory tests and vital signs. Vitals at every visit; labs per schedule; ECG at screening, baseline and Day 1 of each neoadjuvant cycle. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Efficacy: RFS defined as time from surgical resection to disease recurrence or death from any cause, whichever occurs first, by RECIST v1.1. Additional Efficacy: 1. R0 resection rate, defined as the percentage of cases having a pathologically complete resection with a negative resection margin 2. ORR by RECIST v1.1 3. DOR by RECIST v1.1 4. iRFS, iORR, and iDOR by iRECIST 5. OS, defined as time from start of study treatment to death resulting from any cause 6. Major pathologic response, defined as College of American Pathologists Tumor Regression Grading (CAP TRG) of 0 or 1 at time of surgical resection 7. Biochemical response, defined as >50% decrease in CA 19-9 from baseline Imaging-based endpoints (ORR/DOR; iORR/iDOR; progression by iRECIST) measured every 8 weeks (±1) from first dose until last dose or iCPD. R0 rate, CAP-TRG and major pathologic response measured at surgical resection (=8 months from first dose). Biochemical response (CA19-9) at baseline and Day 1 each cycle. RFS measured from resection to recurrence/death; OS from first dose to death; survival/post-treatment therapies captured every 12 weeks (±2) during follow-up to 104 weeks post-last dose. | — |
Countries
England, United Kingdom, United States of America
Contacts
Public ContactPhillip Trieu
Outcome results
None listed