Clinical trial NCT06048081: Early Access Program for Zolbetuximab
Official title: A Global, Multicenter, Open-label, Early Access Program for Zolbetuximab (IMAB362) Plus mFOLFOX6 or CAPOX in Patients With Claudin18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Study type: EXPANDED_ACCESS
Overall status: AVAILABLE
Conditions: Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma Cancer
Locally Advanced Unresectable Gastric Adenocarcinoma Cancer
Metastatic Gastric Adenocarcinoma Cancer
Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma
Keywords: Zolbetuximab
IMAB362
Modified oxaliplatin, folinic acid (leucovorin) and fluorouracim (FOLFOX6)
Capecitabine and oxaliplatin (CAPOX)
Early Access Program (EAP)
Human epidermal growth factor receptor 2 (HER2) Negative
Claudin 18.2
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2023-09-21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT

Brief summary: This program is to provide zolbetuximab to people with stomach cancer or gastroesophageal junction (the junction between stomach and esophagus) cancer who have not yet been treated with chemotherapy, immunotherapy, or zolbetuximab and who have tested positive for claudin18.2 (a protein found in some cancer cells). People will work with their doctor to see if they are capable of being treated with zolbetuximab while they receive other standard medicines to treat their cancer. The program will allow people early access to zolbetuximab before the drug is fully approved.

Zolbetuximab will be given through a vein. This is called an infusion. The infusion will happen during a person's treatment with other cancer medicines. Zolbetuximab will be given every 3 weeks. People will continue treatment until: they have medical problems (unwanted side effects) from the treatment; their cancer gets worse; they start other cancer treatment; they ask to stop treatment; or they do not come back for treatment.

People will visit the clinic on certain days during their treatment. During these visits, the program doctors will check for any medical problems (unwanted side effects) from zolbetuximab, other cancer treatment, or both. At some visits, other checks will include a medical examination, laboratory tests and vital signs. Vital signs include temperature, pulse, and blood pressure. Also, blood samples will be taken.

People will visit the clinic within 7 days after stopping treatment. The program doctors will check for any medical problems (unwanted side effects) from zolbetuximab or their cancer treatment. Other checks will include a medical examination, laboratory tests, and vital signs. Then, people will have a follow-up visit about 30 days after stopping treatment. If people are having no health problems, the follow-up visit can happen over the telephone.

Detailed description: The European Union European Medicines Agency, the United States Food and Drug Administration, and South Korea Pharmaceuticals and Medical Devices Agency have approved zolbetuximab for the treatment of advanced stomach/GEJ cancer in adults. Enrollment is closed in United States, and Germany.

Eligibility criteria: Inclusion Criteria:

* Patient has histologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
* Patient has confirmed locally advanced, unresectable or metastatic gastric or GEJ adenocarcinoma.
* Patient whose tumor expresses claudin18.2 (CLDN18.2) in ≥ 75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining as determined by local or central immunohistochemistry (IHC) testing.
* Patient has a Human epidermal growth factor receptor 2 (HER2-negative) tumor by local testing on a gastric or GEJ tumor specimen.
* Patient has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Patient must meet all of the following criteria based on the locally analyzed laboratory tests collected.

  * Hemoglobin (Hgb) ≥ 9 g/dL. Patients requiring transfusions are eligible if they have post-transfusion Hgb ≥ 9 g/dL.
  * Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
  * Platelets ≥ 100 × 109/L
  * Albumin ≥ 2.5 g/dL
  * Total bilirubin (TBL) ≤ 1.5 × ULN without liver metastases (or \< 3.0 × ULN if liver metastases are present)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) without liver metastases (or ≤ 5 × ULN if liver metastases are present)
  * Estimated creatinine clearance ≥ 30 mL/min
  * Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time ≤ 1.5 × ULN (except for patients receiving anticoagulation therapy)
* Female patient is not pregnant and at least 1 of the following conditions apply:

  * Not a woman of child bearing potential (WOCBP)
  * WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 9 months after the final administration of oxaliplatin and 6 months after final administration of other interventions.
* Female patient must agree not to breastfeed starting at screening and throughout the EAP period and for 6 months after final intervention administration.
* Female patient must not donate ova starting at first administration of treatment and throughout the EAP period and for 9 months after the final administration of oxaliplatin and 6 months after final administration of other interventions.
* Male patient with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 6 months after final treatment administration.
* Male patient must not donate sperm during the treatment period and for 6 months after final treatment administration.
* Male patient with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the EAP period and for 6 months after final treatment administration.

Exclusion Criteria:

* Patient has previously received treatment in a clinical trial of zolbetuximab, or a clinical trial that included zolbetuximab as 1 of the treatment options, even if the patient was not given zolbetuximab.
* Patient is a candidate for an ongoing clinical trial of zolbetuximab.
* Patient has received any investigational therapy within 28 days or 5 half-lives prior to screening.
* Patient has a known or suspected hypersensitivity to zolbetuximab, other monoclonal antibodies or any components of the formulation used.
* Patient has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, patient may have received either neo-adjuvant or adjuvant chemotherapy, immunotherapy or other systemic anticancer therapies as long as it was completed at least 6 months prior to participation.
* Patient has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma ≤ 14 days prior to program registration and has not recovered from any related toxicity.
* Patient receiving treatment with herbal medications that have known antitumor activity.
* Patient has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to registration. Patients using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg/day of hydrocortisone or up to 10 mg/day of prednisone), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
* Patient has a prior severe allergic reaction, known (immediate or delayed) or suspected hypersensitivity, intolerance or contraindication to zolbetuximab, mFOLFOX6, CAPOX, other monoclonal antibodies or any components of the formulations used.
* Patient has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements.)
* Patient has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
* Patient has significant gastric bleeding and/or untreated gastric ulcers that would exclude the patient from participation.
* Patient has any other condition, which makes the patient unsuitable to receive or tolerate zolbetuximab.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Morristown
country: United States
facility: Site US10001
state: New Jersey
city: Belem
country: Brazil
facility: BR55009
city: Belo Horizonte
country: Brazil
facility: BR55001
city: Brasília
country: Brazil
facility: BR55004
city: Florianópolis
country: Brazil
facility: BR55002
city: Londrina
country: Brazil
facility: BR55007
city: Manaus
country: Brazil
facility: BR55010
city: Natal
country: Brazil
facility: BR55008
city: Porto Alegre
country: Brazil
facility: BR55005
city: Rio De Janeiro
country: Brazil
facility: BR55003
city: Sao Paulo
country: Brazil
facility: BR55006
city: Angers
country: France
facility: FR33004
city: Angers
country: France
facility: FR33010
city: Avignon
country: France
facility: FR33028
city: Bordeaux
country: France
facility: FR33007
city: Bordeaux
country: France
facility: FR33015
city: Brest
country: France
facility: FR33025
city: Cagnes-Sur-Mer
country: France
facility: FR33021
city: Clermont Ferrand
country: France
facility: FR33013
city: Clermont Ferrand
country: France
facility: FR33024
city: Colmar
country: France
facility: FR33026
city: Corbeil Essonnes
country: France
facility: FR33029
city: Le Blanc Mesnil
country: France
facility: FR33020
city: Lormont
country: France
facility: FR33014
city: Lyon
country: France
facility: FR33003
city: Lyon
country: France
facility: FR33031
city: Marseille
country: France
facility: FR33001
city: Montpellier
country: France
facility: FR33008
city: Nantes
country: France
facility: FR33032
city: Niort
country: France
facility: FR33035
city: Paris
country: France
facility: FR33006
city: Paris
country: France
facility: FR33011
city: Paris
country: France
facility: FR33017
city: Paris
country: France
facility: FR33033
city: Paris
country: France
facility: FR33034
city: Perigueux
country: France
facility: FR33012
city: Perpignan
country: France
facility: FR33022
city: Rodez
country: France
facility: FR33016
city: Rouen
country: France
facility: FR33037
city: St Gregoire
country: France
facility: FR33023
city: St. Malo
country: France
facility: FR33018
city: Suresnes
country: France
facility: FR33005
city: Suresnes
country: France
facility: FR33009
city: Trevenans
country: France
facility: FR33036
city: Vannes
country: France
facility: FR33002
city: Vantoux
country: France
facility: FR33030
city: Villejuif
country: France
facility: FR33019
city: Villejuif
country: France
facility: FR33027
city: Berlin
country: Germany
facility: DE49020
city: Chemnitz
country: Germany
facility: DE49021
city: Damme
country: Germany
facility: DE49004
city: Damme
country: Germany
facility: DE49034
city: Erkelenz
country: Germany
facility: DE49006
city: Erkelenz
country: Germany
facility: DE49030
city: Essen
country: Germany
facility: DE49029
city: Frankfurt am Main
country: Germany
facility: DE49017
city: Frankfurt
country: Germany
facility: DE49018
city: Goettingen
country: Germany
facility: DE49003
city: Hamburg
country: Germany
facility: DE49007
city: Hamburg
country: Germany
facility: DE49033
city: Kempten
country: Germany
facility: DE49022
city: Kiel
country: Germany
facility: DE49008
city: Kiel
country: Germany
facility: DE49024
city: Koblenz
country: Germany
facility: DE49023
city: Magdeburg
country: Germany
facility: DE49019
city: Munich
country: Germany
facility: DE49010
city: München
country: Germany
facility: DE 49005
city: Nuernberg
country: Germany
facility: DE49012
city: Ravensburg
country: Germany
facility: DE49025
city: Thuine
country: Germany
facility: DE49032
city: Tübingen
country: Germany
facility: DE49001
city: Ulm
country: Germany
facility: DE49002
city: Viersen
country: Germany
facility: DE49011
city: Wiesbaden
country: Germany
facility: DE49016
city: Incheon
country: Korea, Republic of
facility: KR82004
city: Seongnam-Si
country: Korea, Republic of
facility: KR82008
city: Seoul
country: Korea, Republic of
facility: KR82001
city: Seoul
country: Korea, Republic of
facility: KR82002
city: Seoul
country: Korea, Republic of
facility: KR82003
city: Seoul
country: Korea, Republic of
facility: KR82006
city: Seoul
country: Korea, Republic of
facility: KR82007
city: Suwon-Si
country: Korea, Republic of
facility: KR82009
city: Suwon-Si
country: Korea, Republic of
facility: KR82010
city: Ulsan
country: Korea, Republic of
facility: KR82011
city: Yangsan-Si
country: Korea, Republic of
facility: KR82005
city: Singapore
country: Singapore
facility: SG65001
city: Singapore
country: Singapore
facility: SG65002
city: Singapore
country: Singapore
facility: SG65003
city: Singapore
country: Singapore
facility: SG65004
city: Singapore
country: Singapore
facility: SG65005
city: Singapore
country: Singapore
facility: SG65006
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: