First Line Treatment in Subjects with Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma MedDRA version: 20.0 Level: LLT Classification code 10033599 Term: Pancreatic adenocarcinoma metastatic System Organ Class: 100000004864
Conditions
Interventions
Product Name: Zolbetuximab
Product Code: IMAB362
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Zolbetuximab
Sponsors
Astellas Pharma Global Development, Inc. (APGD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act Authorization for United States sites) must be obtained from the subject or legally authorized representative prior to any study related procedures (including withdrawal of prohibited medication, if applicable). 2. Subject is considered an adult according to local regulation at the time of signing informed consent. 3. Subject agrees not to participate in another interventional study while receiving study drug in present study. 4. A female subject is eligible to participate if she is not pregnant or lactating and at least 1 of the following conditions applies: ? Not a woman of childbearing potential (WOCBP) as defined in the Protocol. OR ? WOCBP who agrees to follow the contraceptive guidance as defined in the Protocol throughout the treatment period and for at least 6 months after the final study drug administration. 5. 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. 6. Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration. 7. A male subject with female partner(s) of child-bearing potential must agree to use contraception as detailed in the Protocol during the treatment period and for at least 6 months after the final study drug administration. 8. A male subject must not donate sperm during the treatment period and for at least 6 months after the final study drug administration. 9. 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. Disease Specific Criteria 10. Subject has histologically or cytologically confirmed adenocarcinoma of pancreas. 11. Subjects must have metastatic pancreatic cancer that has not been previously treated with chemotherapy. ? Prior treatment with 5-FU or GEM administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed (if there is lingering toxicity, then the sponsor should be consulted). ? If a subject received therapy in the adjuvant setting, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of adjuvant therapy. 12. Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1 within 28 days prior to the first dose of study treatment. For subjects with only 1 measureable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy. 13. Subject's tumor sample has CLDN18.2 expression in = 75% of tumor cells demonstrating moderate to strong membranous staining as determined by cent
Exclusion criteria
Exclusion criteria: Subject will be excluded from participation if any of the following apply: Prohibited Treatment or Therapies 1. Subject has received other investigational treatment within 28 days prior to screening. 2. Subject has received radiotherapy for metastatic pancreatic adenocarcinoma within 28 days prior to the first dose of study treatment. Subject who received palliative radiotherapy to peripheral bone metastases = 14 days prior to first dose of study treatment and has recovered from all acute toxicities is eligible. 3. Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subject using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone) or a single dose of systemic corticosteriods is eligible. Medical History or Concurrent Disease 4. Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibody, including humanized or chimeric antibodies. 5. Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment. 6. Subject has a known history of a positive test for human immunodeficiency virus infection or known active Hepatitis B (positive HBs antigen [Ag]) or Hepatitis C infection. For subjects who are negative for HBs Ag, but Hepatitis B core antibody positive, a Hepatitis B virus DNA test will be performed and if positive, the subject will be excluded. Subjects with positive serology but negative Hepatitis C virus RNA test results are eligible. 7. Subject has a history of interstitial pneumonia or pulmonary fibrosis. 8. Subject has pleural effusion or ascites = Grade 3 per CTCAE v 4.0. 9. Subject has an active autoimmune disease that has required systemic treatment in the past 2 years. 10. Subject has active infection requiring systemic therapy that has not completely resolved per investigator judgment within 14 days prior to first dose of study treatment. 11. Subject has significant cardiovascular disease, including: ? 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 administration of first dose of study treatment; ? History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes); ? QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects; ? Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to first dose of study treatment are eligible.) 12. Subject has known active or treated central nervous system metastases and/or carcinomatous meningitis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To confirm the recommended phase 2 dose (RP2D) of zolbetuximab in combination with Nab-P + GEM for subjects with CLDN18.2 positive, metastatic pancreatic adenocarcinoma (Safety Lead-in Phase) -To determine antitumor activity of zolbetuximab measured by the OS in combination with Nab-P + GEM for subjects with CLDN18.2 positive, metastatic pancreatic adenocarcinoma (Randomization Phase) -To assess the safety and tolerability of zolbetuximab in combination with Nab-P + GEM ; Secondary Objective: Key Secondary: ? To evaluate additional antitumor activities of zolbetuximab in combination with Nab-P + GEM measured by PFS and ORR (Randomization Phase) Secondary: ? To evaluate pharmacokinetics of Nab-P + GEM in combination with zolbetuximab (Randomization Phase) ? To evaluate additional antitumor activities measured by disease control rate (DCR) and duration of response (DOR) (Randomization Phase) ? To evaluate the change in serum CA19-9 (Randomization Phase) ? To evaluate pharmacokinetics and immunogenicity of zolbetuximab in combination with Nab-P + GEM ; Primary end point(s): Primary Endpoints ? Confirm RP2D as assessed by DLTs (Safety Lead-in Phase) ? Safety and tolerability as measured by AEs, laboratory test results, vital signs, ECGs and ECOG performance status. ? OS, defined as the time from the date of randomization until the date of death from any cause ; Timepoint(s) of evaluation of this end point: The primary endpoints will be evaluated at the time of interim analysis. All endpoints will be evaluated at primary analysis. A futility analysis will be conducted by the IDMC when 42 OS events are observed. The primary analysis wil | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary (Randomization): ? PFS, defined as the time from the date of randomization until the date of radiological PD per RECIST 1.1 by local investigator evaluation, or death from any cause, whichever is earliest ? ORR, defined as the proportion of subjects who have a best overall response of CR or PR as assessed by local investigator evaluation per RECIST 1.1 Secondary: ? Pharmacokinetic parameters of zolbetuximab, Nab-P (measured as PTX) and GEM (AUCinf, AUCinf [%extrap], AUClast, Cmax, Ctrough, tmax, t1/2, , tlast, CL, Vz, as appropriate) ? DCR, defined as the proportion of subjects who have a best overall response of CR, PR or stable disease (SD) as assessed by local investigator evaluation per RECIST 1.1 ? DOR, defined as the time from the date of the first response (CR/PR) until the date of PD as assessed by local investigator evaluation per RECIST 1.1 or date of death from any cause, whichever is earliest ? Serum CA19-9 change from baseline ? Immunogenicity of zolbetuximab as measured by the frequency of anti-drug antibody (ADA) positive subjects The primary and key secondary endpoints will be evaluated at the time of interim analysis. All endpoints will be evaluated at primary analysis. ; Timepoint(s) of evaluation of this end point: The key secondary endpoints will be evaluated at the time of interim analysis. All endpoints will be evaluated at primary analysis. A futility analysis will be conducted by the IDMC when 42 OS events are observed. The primary analysis will occur once 83 OS events have been observed | — |
Countries
Australia, France, Germany, Ireland, Italy, Japan, Korea, Republic of, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactService Desk - Global Clinical Dev.
Astellas Pharma Europe B.V.
Outcome results
None listed