A Study of Zolbetuximab (IMAB362) in Adults with Pancreatic Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astellas Pharma Global Development Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Mar 2019 → ongoing

Decision date (initial)

2024-07-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-510985-17-00

EudraCT number

2018-002551-15

ClinicalTrials.gov

NCT03816163

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Efficacy, Therapy

- 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 assess whether treatment with zolbetuximab in combination with Nab-P + GEM improves overall survival (OS) compared to Nab-P + GEM in 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 objectives 1

1. To assess whether treatment with zolbetuximab in combination with Nab-P + GEM improves progression-free survival (PFS) and objective response rate (ORR) compared to Nab-P + GEM in subjects with CLDN18.2 positive, metastatic pancreatic adenocarcinoma

Conditions and MedDRA coding

First Line Treatment in Subjects with Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma.

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

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 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.
10. Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.
11. Subjects must have metastatic pancreatic adenocarcinoma 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 adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the adjuvant therapy. • Subjects whose disease progressed on prior treatment with Nab-P and GEM are not eligible.
12. 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 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 central IHC testing. Physical or Laboratory Findings
14. Subject has ECOG performance status of 0 or 1
15. Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
16. Subject must meet all of the following criteria based on the laboratory tests collected within 14 days prior to randomization. In case of multiple laboratory data within this period, the most recent data should be used. •Hemoglobin ≥ 9 g/dl (no transfusion within 14 days of start of study treatment) •Absolute neutrophil count ≥ 1.5 x 109 /L •Platelets ≥ 100 x 109 /L •Albumin ≥ 2.5 g/dL •Total bilirubin ≤ 1.5 x upper limit of normal (ULN) •Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN without liver metastases (≤ 5 x ULN if liver metastases are present) •Estimated creatinine clearance ≥ 30 mL/min •Prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)

Exclusion criteria 18

1. Subject has received other investigational treatment within 28 days prior to randomization.
2. Subject has received radiotherapy for metastatic pancreatic adenocarcinoma ≤ 14 days prior to randomization and has not recovered from any related toxicity.
3. Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. 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), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
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. NOTE: Screening for these infections should be conducted per local requirements. 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. Subjects treated for hepatitis C with undetectable viral load 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 4.03.
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 randomizatio
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 randomization; ● 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 randomization are eligible.)
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 v.4.03 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 per investigator's judgment.
17. Subject has another malignancy for which treatment is required per investigator's clinical judgment
18. Subject has any concurrent disease, infection or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data in the opinion of the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ● 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

Secondary endpoints 9

1. ● 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
2. ● 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
3. Pharmacokinetic parameters of zolbetuximab, Nab-P and GEM (AUCinf, AUCinf [%extrap], AUClast, Cmax, Ctrough, tmax, t1/2, tlast, CL, Vz, as appropriate
4. 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
5. ● 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 earlies
6. Time to worsening of pancreatic pain and GHS/QoL as measured by QLQ-C30, QLQ-PAN26, and PGIS as key HRQOL endpoints
7. HRQoL, as collected viameasured by EORTC QLQ-C30, EORTC QLQPAN26 (including remaining domains besides pancreatic pain), EORTC QLQ-C30 (including remaining domains besides GHS/QoL), EQ-5D-5L, PGIS and PGIC questionnaires
8. Serum CA19-9 change from baseline
9. Immunogenicity of zolbetuximab as measured by the frequency of anti-drug antibody (ADA) positive subjects.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astellas Pharma Global Development Inc.

Sponsor organisation

Astellas Pharma Global Development Inc.

Address

2375 Waterview Drive

City

Northbrook

Postcode

60062-6111

Country

United States

Scientific contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Head of Clinical Trial Unit Regulatory Affairs

Public contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Head of Clinical Trial Unit Regulatory Affairs

Third parties 19

Locations

4 EU/EEA countries · 46 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications