Clinical trial NCT04260191: Study of AMG 910 in Subjects With CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma
Official title: A Global Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of the Half-life Extended Bispecific T-cell Engager AMG 910 in Subjects With Claudin 18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Gastric and Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-02-07
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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) and depending on country-specific standards and approvals.
* 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.
* Subjects with stable condition and anti-coagulative therapy ongoing for at least 1 month, no obvious signs and symptoms of bleeding, and coagulation parameters are fulfilled.
* Subjects should be able to use proton pump inhibitors.

Exclusion Criteria:

* Any anticancer therapy or immunotherapy within 4 weeks of start of first dose (14 days for palliative radiation).
* 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.
* Subjects with inherited bleeding disorders (eg, Willebrand's disease, hemophilia A and other clotting factor deficiency) and subjects with known heparin-induced thrombocytopenia.
* Subjects requiring non-steroidal anti-inflammatory drugs (NSAIDs) during study treatment. The NSAID(s) should be stopped within 7 days prior to start of treatment.

Primary outcomes:
measure: Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
timeFrame: Day 1 to Day 28
measure: Number of Participants Who Experienced a Treatment-emergent AE (TEAE)
timeFrame: Day 1 to 30 days post-last dose; maximum duration was 10.97 months
Secondary outcomes:
measure: Maximum Serum Concentration (Cmax) of AMG 910
timeFrame: Cycle 1: Days 1-7 at pre-infusion, 1, 2, 4, 24, 48, 72, 96, 120 and 144 hr; Days 8 and 10* at pre-infusion, EOI, 4 and 24 hr post-EOI; Days 15, 17* and 22* at pre-infusion and EOI; Day 24* at pre-infusion, EOI, 2, 4 and 24 hr post-EOI (*=Cohort 1 only)
measure: Minimum Serum Concentration (Ctrough) of AMG 910
timeFrame: Cycle 1: Days 1-7 at pre-infusion, 1, 2, 4, 24, 48, 72, 96, 120 and 144 hr; Days 8 and 10* at pre-infusion, EOI, 4 and 24 hr post-EOI; Days 15, 17* and 22* at pre-infusion and EOI; Day 24* at pre-infusion, EOI, 2, 4 and 24 hr post-EOI (*=Cohort 1 only)
measure: Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC0_168hr)
timeFrame: Cycle 1 Day 1 at pre-infusion, 1, 2, 4, 24, 48, 72, 96, 120 and 144 hr after infusion start and Cycle 1 Day 8 pre-infusion through 168 hr post-EOI
measure: Cohort 1 Only: Accumulation Ratio (AR) of AMG 910
timeFrame: Cycle 1 Day 8 pre-infusion and Cycle 1 Day 22 pre-infusion
measure: Half-life (t1/2) of AMG 910
timeFrame: Cycle 1: Days 1-7 at pre-infusion, 1, 2, 4, 24, 48, 72, 96, 120 and 144 hr; Days 8 and 10* at pre-infusion, EOI, 4 and 24 hr post-EOI (*=Cohort 1 only)
measure: Number of Participants With an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Day 1 to end of study (EOS); maximum time on study was 18.76 months
measure: ORR Per Immune RECIST (iRECIST)
timeFrame: Day 1 to EOS; maximum time on study was 18.76 months
measure: Duration of Response (DOR) Per RECIST 1.1
timeFrame: Day 1 to EOS; maximum time on study was 18.76 months
measure: DOR Per iRECIST
timeFrame: Day 1 to EOS; maximum time on study was 18.76 months
measure: Time to Progression Per RECIST 1.1
timeFrame: Day 1 to EOS; maximum time on study was 18.76 months
measure: Time to Progression Per iRECIST
timeFrame: Day 1 to EOS; maximum time on study was 18.76 months
measure: Progression-free Survival (PFS) Per RECIST 1.1
timeFrame: 6 months and 1 year
measure: PFS Per iRECIST
timeFrame: 6 months and 1 year
measure: Overall Survival
timeFrame: 1 year and 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Orange
country: United States
facility: University of California at Irvine Medical Center
state: California
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf Onkologisches Zentrum
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: München
country: Germany
facility: Klinikum der Universität München Campus Grosshadern
city: München
country: Germany
facility: Klinikum rechts der Isar
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - location VUmc
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: