Clinical trial NCT05322577: A Study Evaluating Bemarituzumab in Combination With Other Anti-cancer Therapies in Subjects With Previously Untreated Advanced Gastric or Gastroesophageal Junction Cancer.
Official title: A Phase 1b/2 Study Evaluating the Safety, Tolerability, Efficacy, and Pharmacokinetics of Bemarituzumab in Combination With Other Anti-cancer Therapies in Subjects With Previously Untreated Advanced Gastric or Gastroesophageal Junction Cancer (FORTITUDE-103).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastric Cancer
Gastroesophageal Junction Cancer
Keywords: Gastric Cancer
Gastroesophageal Junction Cancer
Bemarituzumab
FGFR2b Overexpression
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2022-04-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The main objectives of this study are to evaluate the safety and tolerability of bemarituzumab in combination with other anti-cancer therapies, and to evaluate the efficacy of bemarituzumab in combination with S-1 and oxaliplatin (SOX) and nivolumab as assessed by objective response.


Eligibility criteria: Inclusion Criteria:

* Adults with unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer not amendable to curative therapy.
* Ability to provide tumor sample, either archival (obtained within 6 months to joining study) or fresh biopsy.
* For certain arms for Part 1, FGFR2b overexpression positive defined as any FGFR2b 2+/3+ TC determined by centrally performed immunohistochemistry (IHC), based on tumor sample provided.
* For Part 2, FGFR2b overexpression positive defined as FGFR2b ≥10% 2+/3+ TC determined by centrally performed IHC testing, based on tumor sample provided.
* Easter Cooperative Oncology Group (ECOG) performance score less than or equal to 1.
* Measurable or non-measurable disease as long as evaluable by Response Evaluation Criteria Solid Tumors (RECIST) version 1.1
* Participant has no contradictions to CAPOX/SOX plus or minus nivolumab.
* Adequate organ function.
* For Part 2, measurable disease according to RECIST v1.1.

Exclusion Criteria:

* Prior treatment for metastatic or unresectable disease (Note: prior adjuvant or neo-adjuvant therapy for local disease is allowed if ended more than 6 months of 1st dose).
* Prior treatment with any selective inhibitor of fibroblast growth factor - fibroblast growth factor receptor (FGF-FGFR) pathway.
* Known human epidermal growth factor receptor 2 (HER2) positive
* Untreated or symptomatic central nervous system (CNS) disease or brain metastases.
* Peripheral sensory neuropathy greater than or equal to Grade 2.
* Clinically significant cardiac disease.
* Other malignancy within the last 2 years (exceptions for definitively treated disease).
* Chronic or systemic ophthalmological disorders.
* Major surgery or other investigational study within 28 days of first study treatment dose.
* Palliative radiotherapy within 14 days of first study treatment dose.
* Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer.
* History or evidence of systemic disease or ophthalmological disorders requiring chronic use of ophthalmic corticosteroids.

Primary outcomes:
measure: Part 1: Number of Participants Who Experience a Dose-limiting Toxicity (DLT)
timeFrame: Day 1 up to Day 21
measure: Part 1: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
timeFrame: Day 1 to end of treatment (up to approximately 1 year)
measure: Part 2: Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
timeFrame: Up to 30 Months
Secondary outcomes:
measure: Part 1: Area Under the Concentration-time Curve (AUC) of Bemarituzumab
timeFrame: Day 1 to end of treatment (up to approximately 1 year)
measure: Part 1: Maximum Observed Concentration (Cmax) of Bemarituzumab
timeFrame: Day 1 to end of treatment (up to approximately 1 year))
measure: Part 1: Observed Concentration at the end of a Dose Interval (Ctrough) of Bemarituzumab
timeFrame: Day 1 to end of treatment (up to approximately 1 year)
measure: Part 1: OR per RECIST v1.1
timeFrame: Up to 2 years
measure: Part 1: Duration of Response (DoR) per RECIST v1.1
timeFrame: Up to 2 years
measure: Part 1: Disease Control Rate (DCR)
timeFrame: Up to 2 years
measure: Part 1: Progression-free Survival (PFS) per RECIST v1.1
timeFrame: Up to 2 years
measure: Part 1: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Part 2: Number of Participants Who Experience TEAEs
timeFrame: Up to 30 months
measure: Part 2: DoR per RECIST v1.1
timeFrame: Up to 30 months
measure: Part 2: Time to Response (TTR) per RECIST v1.1
timeFrame: Up to 30 months
measure: Part 2: Disease Control (DC) per RECIST v1.1
timeFrame: Up to 30 months
measure: Part 2: PFS per RECIST v1.1
timeFrame: Up to 30 months
measure: Part 2: OS
timeFrame: Up to 30 months
Other outcomes:
Locations:
city: Northport
country: United States
facility: Northport Veterans Affairs Medical Center
state: New York
city: Toyoake-shi
country: Japan
facility: Fujita Health University Hospital
state: Aichi
city: Hirosaki-shi
country: Japan
facility: Hirosaki University Hospital
state: Aomori
city: Chiba-shi
country: Japan
facility: Chiba University Hospital
state: Chiba
city: Matsuyama-shi
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Fukui-Shi
country: Japan
facility: Fukui Prefectural Hospital
state: Fukui
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
state: Fukuoka
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital
state: Fukushima
city: Gifu-shi
country: Japan
facility: Gifu University Hospital
state: Gifu
city: Ogaki-shi
country: Japan
facility: Ogaki Municipal Hospital
state: Gifu
city: Maebashi-shi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Ota-shi
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Hiroshima-shi
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
state: Hiroshima
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima
city: Kasama-shi
country: Japan
facility: Ibaraki Prefectural Central Hospital
state: Ibaraki
city: Kanazawa-shi
country: Japan
facility: Ishikawa Prefectural Central Hospital
state: Ishikawa
city: Kita-gun
country: Japan
facility: Kagawa University Hospital
state: Kagawa
city: Kawasaki-shi
country: Japan
facility: St Marianna University Hospital
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
state: Kanagawa
city: Kochi-shi
country: Japan
facility: Kochi Health Sciences Center
state: Kochi
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital
state: Kyoto
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Okayama-shi
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Osaka-shi
country: Japan
facility: Osaka General Medical Center
state: Osaka
city: Takatsuki-shi
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital
state: Osaka
city: Shizuoka-shi
country: Japan
facility: Shizuoka General Hospital
state: Shizuoka
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Shimotsuga-gun
country: Japan
facility: Dokkyo Medical University Hospital
state: Tochigi
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Minato-ku
country: Japan
facility: IMSUT Hospital, The Institute of Medical Science The University of Tokyo
state: Tokyo
city: Toyama-shi
country: Japan
facility: Toyama University Hospital
state: Toyama
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
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: Singapore
country: Singapore
facility: National University Hospital
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: