This is a Phase II non-randomized, single arm, open label study of abemaciclib in combination
with pembrolizumab in patients with unresectable or metastatic gastric, gastroesophageal
junction, or esophageal adenocarcinoma who have received at least two lines of prior therapy.
Treatment will be administered in 21-day cycles. Pembrolizumab will be administered
intravenously (IV) at a dose of 200 mg on day 1 of each cycle. Abemaciclib will be taken
orally twice a day on each day of the cycle, 150 mg per dose. Treatment will continue until
disease progression or development of unacceptable toxicities.
- Patients with histologically confirmed metastatic or locally advanced unresectable
gastric, gastroesophageal junction or esophageal adenocarcinoma.
- Be willing and able to provide written informed consent for the trial.
- Age >= 18 years at the time of consent.
- Prior treatment with at least two lines of systemic therapy for advanced disease.
Patients who have received neoadjuvant or adjuvant therapy or definitive
chemoradiation and had recurrence during or within 6 months of completion of all
treatments may count adjuvant therapy as one chemotherapy line.
- Presence of measurable disease based on RECIST 1.1 as determined by local site
- ECOG PS 0-1.
- Patients must have discontinued all previous treatments for cancer (including
cytotoxic chemotherapy, molecularly targeted therapy, radiotherapy, and
- Patients who received chemotherapy must have recovered (CTCAE Grade ≤1) from the acute
effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy.
A washout period of at least 21 days is required between last systemic therapy dose
and treatment initiation per protocol.
- A washout period of at least 14 days is required between end of radiotherapy and
- The patient is able to swallow oral medications.
- Demonstrate adequate organ function as defined in the table in the protocol.
- Females of childbearing potential must have a negative serum pregnancy test within 7
days prior to registration. NOTE: Females are considered of child bearing potential
unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least
12 consecutive months.
- Females of childbearing potential must be willing to abstain from heterosexual
activity or to use 2 forms of effective methods of contraception from the time of
informed consent until 60 days after treatment discontinuation. The two contraception
methods can be comprised of two barrier methods, or a barrier method plus a hormonal
- Men who are not surgically sterile (vasectomy) must agree to use an acceptable method
of contraception. Male subjects with female sexual partners who are pregnant, possibly
pregnant, or who could become pregnant during the study must agree to use condoms from
the first dose of study drug through at least 60 days after the last dose of study
drug. Total abstinence for the same time period is an acceptable alternative.
- As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study.
- Provided written informed consent and HIPAA authorization for release of personal
health information, approved by an Institutional Review Board (IRB). NOTE: HIPAA
authorization may be included in the informed consent or obtained separately.
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
- History of prior therapy with CDK4 or CDK6 inhibitors or prior immune checkpoint
- Patients with known microsatellite instability will be excluded.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment. The use of physiologic doses of corticosteroids may be approved after
consultation with the study PI.
- Serious preexisting medical condition(s) that would preclude participation in this
study (for example, interstitial lung disease, severe dyspnea at rest or requiring
oxygen therapy, history of major surgical resection involving the stomach or small
bowel, or a preexisting chronic condition resulting in baseline Grade 2 or higher
- Symptomatic central nervous system metastasis. Screening of asymptomatic patients is
not required for enrollment.
- Personal history of any of the following conditions: syncope of cardiovascular
etiology, ventricular arrhythmia of pathological origin (including, but not limited
to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
- Known additional malignancy that progressed or required active treatment within the
last 2 years. Exceptions include curatively treated basal cell and squamous cell
carcinoma of the skin, curatively resected in situ cervical and/or breast cancers, in
situ or intramucosal pharyngeal cancer, and Gleason 6 prostate cancer with PSA <10.
- Patients who have received a live vaccine within 30 days of planned start of
Note: The killed virus vaccines used for seasonal influenza vaccines for injection are
allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated
vaccines, and are not allowed.
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Active infection requiring systemic therapy.
- Patients who are pregnant or breastfeeding or expecting to conceive or father children
within the projected duration of the trial, starting with the screening visit through
60 days after the last dose of pembrolizumab or abemaciclib. (NOTE: breast milk cannot
be stored for future use while the mother is being treated on study.)