2138-CL-0101 - A Phase 1/1b Study of ASP2138 in Participants with Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma or Metastatic Pancreatic Adenocarcinoma Whose Tumors Have Claudin (CLDN) 18.2 Expression

Studio Clinico

Patologia: Carcinoma del pancreas esocrino, Neoplasie dello stomaco

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1, I B

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

Participant is eligible for participation in the study if all of the following apply:

General Criteria
1. IRB/IEC approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization for US study sites) must be obtained from the participant prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Participant is aged 18 years or older and considered an adult according to local regulation at the time of signing the ICF.
3. Female participant is not pregnant (see [Section 10.2 Appendix 2: Contraception Requirements]), confirmed by serum pregnancy test and medical evaluation by interview and at least 1 of the following conditions apply: a. Not a WOCBP (see [Section 10.2 Appendix 2: Contraception Requirements]) b. WOCBP who agrees to follow the contraceptive guidance (see [Section 10.2 Appendix 2: Contraception Requirements]) from the time of informed consent through at least 6 months after final study intervention administration.
4. Female participant must agree not to breastfeed starting at screening and throughout the study period and for 6 months after the final study intervention administration.
5. Female participant must not donate ova starting at screening and throughout the study period and for 6 months after the final study intervention administration.
6. Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception (see [Section 10.2 Appendix 2 Contraception Requirements]) throughout the treatment period and for 6 months after the final study intervention administration.
7. Male participant must not donate sperm during the treatment period and for 6 months after the final study intervention administration.
8. Male participant with 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 intervention administration.
9. Participant’s tumor sample is positive for CLDN18.2 expression by central IHC testing. If the participant previously had a tumor sample tested for CLDN18.2, the site should contact the sponsor to assess whether those results can be used for eligibility determination; the site should contact the sponsor and provide the prior pathology report to assess whether those results can be used for eligibility. If the pathology report is not available, the site should provide as much information as possible.
10. Participant has radiographically-confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to the first dose of study intervention.
11. Participant has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of study intervention per investigator assessment. For participant 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.
12. Participant has QTcF ≤ 470 msec.
13. Participant agrees not to participate in another interventional study while receiving study treatment in the present study.
14. Participant has ECOG performance status of 0 or 1.
15. Participant has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
16. Participant must meet all of the following criteria based on laboratory tests within 7 days prior to the first dose of study drug. In case of multiple laboratory data within this period, the most recent data should be used. If a participant has received a recent blood transfusion, the laboratory tests must be obtained ≥ 2 weeks after any blood transfusion.

Disease Specific Criteria: Gastric/GEJ Cancer
1. Participant has histologically confirmed gastric or GEJ adenocarcinoma.
2. Participant with gastric or GEJ adenocarcinoma who has progressed, is intolerant, has refused, or for whom there is no standard approved therapies that impart significant clinical benefit based on investigator’s clinical judgment (no limit to the number of prior treatment regimens).

Disease Specific Criteria: Pancreatic Cancer
1. Participant has histologically or cytologically confirmed pancreatic adenocarcinoma.
2. Participant with pancreatic adenocarcinoma who has progressed, is intolerant, has refused, or for whom there is no standard approved therapies that impart significant clinical benefit based on investigator’s judgement (no limit to the number of prior treatment regimens).
Waivers to the inclusion criteria will NOT be allowed.

Criteri di esclusione: 

Participant will be excluded from participation in the study if any of the following apply:
1. Participant has received other investigational agents, or antineoplastic therapy including immunotherapy or devices concurrently or within 21 days or 5 times the half-life, whichever is shorter, prior to first dose of study intervention administration.
2. Participant has any condition, which, in the investigator’s opinion, makes the participant unsuitable for study participation.
3. Participant has known immediate or delayed hypersensitivity or contraindication to any component of study treatment.
4. Participant has had prior severe allergic reaction or intolerance to known ingredients of ASP2138 or other antibodies, including humanized or chimeric antibodies.
5. Participant weighs < 40 kg.
6. Participant has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to first dose of study intervention. Participant 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 daily dose of systemic corticosteroids or receiving systemic corticosteroids as pre-medication for radiologic imaging contrast use are allowed.
7. Participant has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
8. Per investigator judgment, participant has significant gastric bleeding and/or untreated gastric ulcers that exclude the participant from participation.
9. Participant has symptomatic CNS metastases or participant has evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). Participants with previously treated CNS metastases are eligible, if they are clinically stable and have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study treatment and are not requiring immunosuppressive doses of systemic steroids (> 30 mg per day of hydrocortisone or > 10 mg per day of prednisone or equivalent) for longer than 2 weeks.
10. Participant is known to have HIV infection. However, participants with CD4+ T cell counts ≥ 350 cells/µL and no history of AIDS-defining opportunistic infections within the past 6 months are eligible. NOTE: Screening for HIV infection should be conducted per local requirements.
11. Participant is known to have active hepatitis B (positive HBsAg) or hepatitis C infection. Testing is required for known history of these infections or as mandated by local requirements. NOTE: Screening for these infections should be conducted per local requirements.
    • For participant who is negative for HBsAg, but HBc Ab positive, an HBV DNA test will be performed and if positive the participant will be excluded.
    • Participant with positive HCV serology, but negative HCV RNA test results are eligible.
    • Participant treated for HCV with undetectable viral load results are eligible
12. Participant has had within 6 months prior to first dose of study intervention any of the following: unstable angina, myocardial infarction, ventricular arrhythmia requiring intervention or hospitalization for heart failure.
13. Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to the start of study intervention.
14. Participant has active autoimmune disease that has required systemic immunosuppressive treatment within the past 1 month prior to the start of study intervention.
15. Participant has a clinically significant disease or co-morbidity that in the opinion of the investigator may adversely affect the safe delivery of treatment within this study or make the participant unsuitable for study participation.
16. Participant has psychiatric illness or social situations that would preclude study compliance per investigator’s judgment.
17. Participant has had a major surgical procedure 28 days before start of study intervention and has not fully recovered, per investigator’s clinical judgment.
18. Participant has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ or metastatic pancreatic adenocarcinoma 14 days prior to start of study intervention and has NOT recovered from any related toxicity.
19. Participant has another malignancy for which treatment is required, per investigator’s clinical judgment.
20. Participant who has received an CLDN18.2-targeted investigational agent (e.g., zolbetuximab or chimeric antigen receptor CLDN18.2-specific T cells) prior to first dose of study intervention administration is not eligible for dose escalation cohorts. However, a participant who has received an CLDN18.2-targeted investigational agent greater than 28 days or 5 half-lives (whichever is longer) prior to first dose study intervention administration is eligible for dose expansion cohorts only, with the exception of participants who have experienced Grade ≥ 3 GI toxicity after receiving an CLDN18.2-targeted investigational agent.
21. Participant has a history or complication of interstitial lung disease.
Waivers to the exclusion criteria will NOT be allowed.

Schema di trattamento: 

Treatment will be in cycles of either 7 or 14 days (1 or 2 weeks). In each treatment cycle, intravenous infusions or subcutaneous injections will either be given once a week or once every 2 weeks.

Trattamento sperimentale: 

ASP2138 Injection 0.5 mg/1mL

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

- To evaluate the safety and tolerability of ASP2138
- To determine the MTD and/or RP2D regimen(s) of ASP2138

Obiettivi secondari dello studio: 

- To evaluate the pharmacokinetics of ASP2138
- To evaluate the antitumor activity of ASP2138
- ORR and DCR by RECIST 1.1
- To evaluate changes in CLDN18.2 and PD-L1 tumor expression related to treatment with ASP2138
- To evaluate potential genomic and/or other biomarkers that may correlate with treatment outcome of ASP2138.
- To evaluate the immunogenicity of ASP2138
- To evaluate additional PK parameters of ASP2138
- To evaluate antitumor activity of ASP213

Data di inizio dell'arruolamento: 22.06.2022

Data di fine dell'arruolamento: 26.12.2025

Centri partecipanti

Nord Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: NCT05365581- RCT2031210644

Data di inserimento: 31.07.2024

Data di aggiornamento: 09.09.2024

Promotore

Astellas Pharma Global Development, Inc.

Telefono: 8008887704

Email: Astellas.registration@astellas.com

CRO

ICON Clinical Research

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na