Amivantamab treatment for esophagogastric cancer

Phase II Study of Amivantamab in EGFR or MET- Amplified Esophagogastric Cancer

This study tests if a new drug called amivantamab can help people with esophagogastric cancer that has certain genetic markers and has not responded to previous treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: trastuzumab, chemotherapy, radiation, amivantamab
• Locations: 9 sites (Irvine, California and 8 other locations)
• Trial ID: NCT05117931 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of amivantamab in patients with EGFR- or MET-amplified esophagogastric cancer who have previously undergone treatment. Participants must have measurable disease and meet specific genetic criteria for inclusion. The study aims to determine if amivantamab can provide a beneficial treatment option for this patient population, focusing on both efficacy and side effects.

Who should consider this trial

Good fit: Ideal candidates include adults with previously treated metastatic or unresectable esophagogastric cancer who have specific genetic amplifications and have not received prior EGFR or MET inhibitors.

Not a fit: Patients who have not been previously treated for their esophagogastric cancer or those with tumors that do not exhibit EGFR or MET amplification may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced esophagogastric cancer.

How similar studies have performed: Other studies have shown promise with similar targeted therapies, indicating potential for success with this approach.

Eligibility criteria

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:

A. Hemoglobin ≥9 g/dL

B. ANC ≥1.0 x 10\^9 /L

C. Platelets ≥75 x 10\^9 /L

D. AST and ALT ≤3 x ULN (≤5 x ULN for subjects with liver metastases)

E. Total bilirubin ≤1.5 x ULN; subjects with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits

F. 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.

Where this trial is running

Irvine, California and 8 other locations

• University of California, Irvine — Irvine, California, United States (Recruiting)
• Massachusetts General Hospital (Data Collection Only) — Boston, Massachusetts, United States (Recruiting)
• Memorial Sloan Kettering Basking Ridge (Limited protocol activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (Limited protocol activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Commack (Limited Protocol Activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (Limited protocol activities) — Rockville Centre, New York, United States (Recruiting)

Study contacts

• Principal investigator: Steven Maron, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Steven Maron, MD

Conditions Esophagogastric Cancer; metastatic; unresectable; Amivantamab; EGFR or MET amplified; 21-324