Clinical Trials

Inclusion Criteria - Part 1 and Part 2:

• Subject has provided informed consent prior to initiation of any study specific activities/procedures.
• Age ≥ 18 years old (or legal adult age within country, whichever is older).
• Histologically documented gastric or gastroesophageal junction adenocarcinoma.
• Disease that is unresectable, locally advanced or metastatic (not amendable to curative therapy).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Adequate organ function as follows:
  • Absolute neutrophil count ≥ 1.5 x 10^9 /L;
  • Platelet count ≥ 100 x 10^9 /L;
  • Hemoglobin ≥ 9 g/dl;
  • Aspartate aminotransaminase (AST) and ALT < 3 x ULN (or < 5 x upper limit of normal [ULN] if liver involvement);
  • Total bilirubin < 1.5 x ULN (or < 2 x ULN if liver involvement); with the exception of subjects with Gilbert’s disease).
• Part 1 only:
  • Calculated or measured creatinine clearance (CrCl) of ≥ 50 mL/minute calculated using the formula of Cockcroft and Gault ([140 – Age] × Mass [kg]/[72 × Creatinine mg/dL]).
• Part 2 only:
  • Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/minute calculated using the formula of Cockcroft and Gault ([140 – Age] × Mass [kg]/[72 × Creatinine mg/dL]);
  • INR or prothrombin time (PT) < 1.5 × ULN except for subjects receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to enrollment.
• Measurable disease or non-measurable, but evaluable disease, according to RECIST v1.1.
• Subject must be a candidate to receive mFOLFOX6 and nivolumab.

Additional Criteria for Part 2:

• No prior treatment for metastatic or unresectable disease except for a maximum of 1 dose of mFOLFOX6 with or without nivolumab.
• Prior adjuvant or neo-adjuvant therapy for localized disease is allowed, provided it has been completed more than 6 months prior to the first dose of study treatment.
• FGFR2b overexpression as determined by centrally performed IHC testing.

Exclusion Criteria:

• Untreated or symptomatic CNS metastases and lepto.stable for at least 4 weeks and do not require intervention (including use of corticosteroids).
• Subjects with treated brain metastases are eligible provided the following criteria are met:
  • Definitive therapy was completed at least 2 weeks prior to the first planned dose of study treatment (stereotactic radiosurgery at least 7 days prior to first planned dose of study treatment);
  • At least 7 days prior to first dose of study treatment: any CNS disease is clinically stable, subject is off steroids for CNS disease (unless steroids are indicated for a reason unrelated to CNS disease), and subject is off or on stable doses of anti-epileptic drugs.
  • Impaired cardiac function or clinically significant cardiac disease including: unstable angina within 6 months prior to first dose of study treatment, acute myocardial infarction < 6 months prior to first dose of study treatment, New York Heart Association (NYHA) class II-IV congestive heart failure, uncontrolled hypertension (defined as an average systolic blood pressure > 160 mmHg or diastolic > 100 mm Hg despite optimal treatment (measured following European Society for Hypertension/European Society of Cardiology [ESH/ESC] 2013 guidelines), uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, active coronary artery disease, QTc ≥ 470.
• Peripheral sensory neuropathy grade 2 or higher.
• Active infection requiring systemic treatment or any uncontrolled infection within 14 days prior to first dose of study treatment.
• Known human immunodeficiency virus (HIV) infection with CD4+ T-cell (CD4+) counts < 350 cells/uL, hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response following antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response with antiviral therapy directed at hepatitis B are allowed).
• Any anticancer therapy or immunotherapy within 4 weeks prior to first dose of study treatment (except for a maximum of 1 dose of mFOLFOX6 with or without nivolumab):
  • Palliative radiotherapy is allowed, provided it has been completed more than 14 days prior to the first dose of study treatment;
  • All treatment-related toxicity needs to be resolved to grade ≤ 1 prior to the first dose of study treatment, with the exception of alopecia or toxicities considered irreversible (defined as having been present and stable for > 21 days) which are not otherwise described in the exclusion criteria.
• History of interstitial lung disease.
• Known positive HER2 status (as defined by a positive IHC test of 3+ or IHC2+ with positive fluorescent in situ hybridization [FISH]).
• History or evidence of systemic disease or ophthalmological disorders requiring chronic use of ophthalmic corticosteroids.
• Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or actively progressing.
• Unwillingness to avoid use of contact lenses during study treatment.
• History of solid organ transplantation.
• Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study.
• Immunosuppressive doses of systemic medications of > 10 mg/day or prednisone or equivalent must be discontinued at least 2 weeks before the first dose of study drug. Short courses of high dose corticosteroids and/or continuous low dose prednisone (< 10 mg/day) are allowed. In addition, inhaled, intranasal, intraocular, and/or joint injections of corticosteroids are allowed.
• Subjects who experienced severe, life-threatening or recurrent (Grade 2 or higher) immunemediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immune-oncology agents.
• History of other malignancy within the past 2 years, except:
  • Curatively treated non-melanoma skin malignancy;
  • Cervical cancer in situ;
  • Curatively treated uterine cancer stage I;
  • Curatively treated ductal or lobular breast carcinoma in situ and not currently receiving any systemic therapy;
  • Localized prostate cancer that has been treated surgically with curative intent and presumed cured.
• Evidence of, or recent (within 6 months) history of, corneal defects, corneal ulcerations, keratitis, or keratoconus, history of corneal transplant, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer. Recent (within 6 months) corneal surgery or ophthalmic laser treatment.
• Major surgical procedures within 28 days prior to first dose of study treatment.
  • Minor surgery requiring local/epidural anesthesia must be completed more than 72 hours before first dose of study treatment. In all cases, the subject must be sufficiently recovered and stable before treatment administration.
• Prior treatment with any selective inhibitor of the FGF-FGFR pathway.
• Currently receiving treatment in another investigational device or drug study within 28 days of first dose of study treatment or during this clinical study. Other investigational procedures while participating in this study are excluded.
• Female subjects of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 5 months after the last dose of protocol-mandated therapy.
• Female subjects who are breastfeeding or plan to breastfeed while on study through 3 months after the last dose of protocol-mandated therapy.
• Female subjects planning to become pregnant while on study through 5 months after the last dose of protocol-mandated therapy.
• Female subjects of childbearing potential with a positive pregnancy test assessed at Screening and within 72 hours prior to first dose of study treatment by a highly sensitive urine or serum pregnancy test.
• Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 3 months after the last dose of protocol-mandated therapy.
• Male subjects unwilling to abstain from donating sperm during treatment and for an additional 3 months after the last dose of protocol-mandated therapy.
• Unlikely to be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures within the subject’s capacity to the best of the subject and investigator’s knowledge.
• History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
• Known allergy, hypersensitivity or contraindication to components of the bemarituzumab formulation including polysorbate.

Eligibility last updated 10/22/21. Questions regarding updates should be directed to the study team contact.