Metastatic pancreatic adenocarcinoma
Conditions
Interventions
This study will be in 2 parts.
- Safety Lead-in Phase (Part 1)
Groups of people will receive 1 of 2 different doses of zolbetuximab: a lower dose or a higher dose, both together with chemotherapy.
Sponsors
Astellas Pharma Global Development, Inc. (APGD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A female subject is eligible to participate if she is not pregnant or lactating and at least 1 of the following conditions applies: o Not a woman of childbearing potential (WOCBP) OR o WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final study drug administration. 2. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration. 3.Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration. 4. A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration. 5. A male subject must not donate sperm during the treatment period and for at least 6 months after the final study drug administration. 6. Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration. 7. Subject has histologically or cytologically confirmed adenocarcinoma of pancreas. 8. Subjects must have metastatic pancreatic adenocarcinoma that has not been previously treated with chemotherapy. o Prior treatment with fluorouracil (5-FU) or GEM administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed o If a subject received adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the adjuvant therapy. o Subjects whose disease progressed on prior treatment with Nab-P and GEM are not eligible. 9. Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1 within 28 days prior to randomization. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy. 10. Subject's tumor sample has CLDN18.2 expression in >= 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing 11. Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 12. Subject has predicted life expectancy >= 12 weeks. 13. Subject must meet all of the following criteria based on the laboratory tests that will be collected within 14 days prior to randomization. In case of multiple laboratory data within this period, the most recent data should be used. o Hemoglobin >= 9 g/dl (no transfusion within 14 days of start of study treatment) o Absolute neutrophil count >= 1.5 x 10^9/L o Platelets >= 100 x 10^9/L o Albumin >= 2.5 g/dL o Total bilirubin = 30 mL/min o Prothrombin time/international normalized ratio (INR) and partial thromboplastin time <= 1.5 x ULN (except for subjects receiving anticoagulation therapy)
Exclusion criteria
Exclusion criteria: 1. Subject has received other investigational treatment within 28 days prior to randomization. 2. Subject has received radiotherapy for metastatic pancreatic adenocarcinoma = Grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) v4.03. 9. Subject has an active autoimmune disease that has required systemic treatment in the past 3 months prior to randomization. 10.Subject has active infection requiring systemic therapy that has not completely resolved per investigator judgment within 7 days prior to randomization. 11. Subject has significant cardiovascular disease, including: a) Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization; b) History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes); c) QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects; d) Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to randomization.) 12. Subject has a history of central nervous system metastases and/or carcinomatous meningitis from pancreatic adenocarcinoma. 13. Subject has known peripheral sensory neuropathy >= Grade 2 per CTCAE v4.03 unless the absence of deep tendon reflexes is the sole neurological abnormality. 14.Subject has had a major surgical procedure <= 28 days prior to randomization. 15. Subject without complete recovery from a major surgical procedure <= 14 days prior to randomization. 16. Psychiatric illness or social situations that would preclude study compliance. 17. Subject has another malignancy for which treatm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Confirm the recommended phase 2 dose (RP2D) as assessed by dose-limiting toxicity (DLT)s (Safety Lead-in Phase) - Safety and tolerability as measured by adverse event (AE)s, laboratory test results, vital signs, electrocardiogram (ECG)s, and Eastern Cooperative Oncology Group (ECOG) performance status - Overall survival (OS), defined as the time from the date of randomization until the date of death from any cause | — |
Secondary
| Measure | Time frame |
|---|---|
| - Progression free survival (PFS), defined as the time from the date of randomization until the date of radiological progressive disease (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by local investigator evaluation, or death from any cause, whichever is earliest - Objective response rate (ORR), defined as the proportion of subjects who have a best overall response of complete response (CR) or partial response (PR) as assessed by local investigator evaluation per RECIST 1.1 - Pharmacokinetic parameters of zolbetuximab, Nab-P and GEM (AUCinf, AUCinf [%extrap], AUClast, Cmax, Ctrough, tmax, t1/2, tlast, CL, Vz, as appropriate) - Disease control rate (DCR), defined as the proportion of subjects who have a best overall response of stable disease, CR or PR as assessed by local investigator per RECIST 1.1 - Duration of response (DOR), defined as the time from the date of the first response (CR/PR) until the date of PD as assessed by local investigator per RECIST 1.1 or date of death from any cause, whichever is earliest - Time to improvement of pancreatic pain and time to worsening of global health status (GHS)/quality of life (QoL) (as measured by Quality of Life Questionnaire - Core Questionnaire [QLQ-C30], Quality of Life Questionnaire - Pancreatic Cancer Module 26 [QLQ-PAN26], and Patient Global Impression of Severity [PGIS]) as key Health Related Quality of Life (HRQOL) endpoints - HRQoL, as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-PAN26 (including remaining domains besides pancreatic pain), EORTC QLQ-C30 (including remaining domains besides GHS/QoL), EuroQoL Five Dimensions Questionnaire 5L (EQ-5D-5L), PGIS and Patient Global Impression of Change (PGIC) questionnaires - Serum CA19-9 change from baseline - Immunogenicity of zolbetuximab as measured by the frequency of anti-drug antibody (ADA) positive subjects | — |
Countries
Australia, Brazil, China, France, Ireland, Italy, Japan, Mexico, South Korea, Spain, Taiwan, Turkey, United States of America
Outcome results
None listed