A Study of Amivantamab in People With Esophagogastric Cancer

Overview

The purpose of this study is to see whether the study drug, amivantamab, is an effective treatment for people with EGFR- or MET-amplified esophagogastric cancer. The researchers will also look at whether amivantamab is a safe treatment that causes few or mild side effects in participants.

Eligibility

Inclusion Criteria:

• Subject or legally authorized representative is willing and able to provide written informed consent.
• Patients with previously treated metastatic or unresectable histologically-confirmed esophagogastric cancer who have received at least 1 line of therapy.
• EGFR or MET amplification by tissue-NGS with copy number >8 and/or ctDNA amplification by any FDA and CLIA-approved assay
• No prior receipt of an EGFR or MET inhibitor for esophagogastric cancer. (Note: if a patient previously received a EGFR inhibitor, but subsequently demonstrated a MET amplification, or previously received a MET inhibitor, but subsequently demonstrated an EGFR-amplification, inclusion is permitted).
• Patients with HER2+ (IHC 3+ or IHC 2+/FISH+) tumors must have progressed on trastuzumab.
• Measurable disease based on RECIST 1.1.
• ≥ 18 years of age on day of signing informed consent.
• Have an ECOG performance status of 0, 1, or 2.
• Adequate organ function, defined as:
  1. Hemoglobin ≥9 g/dL
  2. ANC ≥1.0 x 10^9 /L
  3. Platelets ≥75 x 10^9 /L
  4. AST and ALT ≤3 x ULN (≤5 x ULN for subjects with liver metastases)
  5. Total bilirubin ≤1.5 x ULN; subjects with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits
  6. Serum creatinine <1.5 x ULN or if available, calculated or measured creatinine clearance >50 mL/min/1.73 m^2
• Women of childbearing potential and male patients with women of childbearing potential

  partners must be willing to use an adequate method of contraception

Exclusion Criteria:

• Prior chemotherapy, targeted small molecule therapy, or biological therapy, within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent (excluding alopecia).
• If subject received major surgery, they must have recovered adequately prior to starting therapy.
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Known active hepatitis B (e.g., HBsAg reactive or polymerase chain reaction detectable).

        Note: Subjects with a prior history of HBV demonstrated by positive hepatitis B core
        antibody are eligible if they have at Screening 1) a negative HBsAg and 2) a HBV DNA (viral
        load) below the lower limit of quantification, per local testing. Subjects with a positive
        HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower
        limit of quantification, per local testing.
          -  Known active hepatitis C (e.g., HCV RNA [qualitative] is detected).
        Note: Subjects with a prior history of HCV, who have completed antiviral treatment and have
        subsequently documented HCV RNA below the lower limit of quantification per local testing
        are eligible.
          -  Other clinically active or chronic liver disease.
          -  Subject has uncontrolled inter-current illness, including but not limited to poorly
             controlled diabetes, ongoing or active infection (i.e., has discontinued all
             antibiotics for at least one week prior to first dose of study drug), or psychiatric
             illness/social situation that would limit compliance with study requirements. Subjects
             with medical conditions requiring chronic continuous oxygen therapy are excluded.
          -  Pulmonary embolism (PE) and deep vein thrombosis (DVT), within 1 month of start of
             study drug.
          -  Myocardial infarction, unstable angina, stroke, transient ischemic attach (TIA), or
             coronary/peripheral artery bypass graft, or any acute coronary syndrome within 6
             months of start of study drug.
          -  Congestive heart failure defined as New York Heart Association (NYHA) Class III-IV or
             hospitalization for congestive heart failure (any NYHA class) within 6 months of start
             of study drug.
          -  Interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
             requiring treatment with prolonged steroids or other immune suppressive agents that is
             unresolved or resolved within the last 3 months.
          -  Immune-mediated rash from checkpoint inhibitors that has not resolved prior to
             enrollment.
          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial, in the opinion of the treating investigator.
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 6 months after the last dose of trial treatment.
          -  Prisoners, or subjects who are compulsory detained.