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JOURNAL ONKOLOGIE – STUDIE

Study of AMG 910 in Subjects With CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma

Rekrutierend

NCT-Nummer:
NCT04260191

Studienbeginn:
Juni 2020

Letztes Update:
29.12.2020

Wirkstoff:
AMG 910

Indikation (Clinical Trials):
Adenocarcinoma, Esophageal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Amgen

Collaborator:
-

Studienleiter

MD
Study Director
Amgen

Kontakt

Studienlocations (3 von 16)

Alle anzeigen

Studien-Informationen

Brief Summary:

To evaluate the safety and tolerability of AMG 910 in adult subjects, and to determine the

maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Subjects with histologically or cytologically confirmed metastatic or locally advanced

unresectable gastric or GEJ adenocarcinoma positive for CLDN18.2.

- Subjects should not be eligible for curative surgery and should have been refractory

to or have relapsed after two or more prior lines of standard systemic therapy that

included a platinum, a fluoropyrimidine, either a taxane or irinotecan, and an

approved vascular endothelial growth factor receptor (VEGFR) antibody/tyrosine kinase

inhibitor (TKI).

- For subjects eligible for human epidermal growth factor receptor 2 (HER2) directed

therapy, prior systemic therapy should have included a HER2 targeting antibody

approved for treatment of gastric cancer.

- Subjects may also be included if the aforementioned therapeutic options were medically

not appropriate for them. In these cases, the reason(s) why required prior therapies

for gastric cancer were medically not appropriate should be documented in the

subject's electronic case report form (eCRF).

- For dose-expansion only: Subjects with at least 1 measurable lesion greater than or

equal to 10mm which has not undergone biopsy within 3 months of screening scan. This

lesion cannot be biopsied at any time during the study.

Exclusion Criteria:

- Any anticancer therapy or immunotherapy within 4 weeks of start of first dose.

- Untreated or symptomatic central nervous system (CNS) metastases, leptomeningeal

disease, or spinal cord compression

- Autoimmune disorders requiring chronic systemic steroid therapy or any other form of

immunosuppressive therapy while on study, eg, ulcerative colitis, Crohn's disease, or

any other gastrointestinal autoimmune disorder causing chronic nausea, vomiting, or

diarrhea. Recent or current use of inhaled steroids or physiological substitution in

case of adrenal insufficiency is not exclusionary.

- Evidence or history within last 3 months of gastrointestinal inflammatory conditions

not associated with the underlying cancer disease including gastrinomas, duodenitis,

proven gastric ulcer, duodenal ulcer, pancreatitis, or subjects with recent gastric

bleeding. Subjects may be included if the symptomatic/immunosuppressive treatment is

discontinued more than 4 weeks prior to the first dose of AMG 910, symptoms have

resolved, and gastroscopy does not indicate signs of active disease.

Studien-Rationale

Primary outcome:

1. Number of participants with dose-limiting toxicities (DLT) (Time Frame - 2 years):
Subject grade of dose limiting toxicities is the occurrence of any of the toxicities during the DLT evaluation period if judged by the investigator to be related to the administration of AMG 910

2. Number of participants with treatment-emergent adverse events (Time Frame - 2 years)

3. Number of participants with treatment-related adverse events (Time Frame - 2 years)

4. Number of participants with clinically significant changes in vital signs (Time Frame - 2 years)

5. Number of participants with clinically significant changes in electrocardiogram (ECG) (Time Frame - 2 years)

6. Number of participants with clinically significant changes in clinical laboratory tests (Time Frame - 2 years)

Secondary outcome:

1. Maximum serum concentration (Cmax) (Time Frame - 2 years)

2. Minimum serum concentration (Cmin) (Time Frame - 2 years)

3. Area under the concentration-time curve (AUC) over the dosing interval (Time Frame - 2 years)

4. AUC accumulation following multiple dosing (Time Frame - 2 years)

5. Half-life (t1/2) (Time Frame - 2 years)

6. Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST (Time Frame - 2 years)

7. Duration of response (DOR) (Time Frame - 2 years)

8. Time to progression (Time Frame - 2 years)

9. Progression-free survival (PFS) (Time Frame - 6 months and 1 year)

10. Overall survival (OS) (Time Frame - 1 year and 2 years)

Studien-Arme

  • Experimental: Dose-exploration
    The dose-exploration phase of the study will estimate the MTD (Maximum Tolerated Dose) of AMG 910 using a Bayesian logistic regression model (BLRM). A RP2D (Recommended Phase 2 Dose) may be identified based on emerging safety, efficacy, and PD (Pharmacodynamics) data prior to reaching an MTD. Alternative dosing schedule(s) may be explored based on emerging PK (Pharmacokinetics) and safety data.
  • Experimental: Dose-expansion
    The dose-expansion phase will be conducted to confirm safety, PK, and PD at the MTD or RP2D and to obtain further safety and efficacy data and enable correlative biomarker analysis.

Geprüfte Regime

  • AMG 910:
    Dose Exploration Dose Expansion

Quelle: ClinicalTrials.gov


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