Clinical trial NCT05117931: A Study of Amivantamab in People with Esophagogastric Cancer
Official title: Phase II Study of Amivantamab in EGFR or MET- Amplified Esophagogastric Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Esophagogastric Cancer
Keywords: metastatic
unresectable
Amivantamab
EGFR or MET amplified
21-324
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Janssen Pharmaceuticals
First posted: 2021-11-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single arm, phase II study of Amivantamab.
Primary purpose: TREATMENT

Brief summary: 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 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.

Primary outcomes:
measure: objective response rate
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital (Data Collection Only)
state: Massachusetts
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (Limited protocol activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Limited protocol activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Limited Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack (Limited Protocol Activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Limited Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All Protocol Activities)
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Nassau (Limited protocol activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Steven Maron, MD
role: PRINCIPAL_INVESTIGATOR
References: