This is a phase II study of OBP-301 with pembrolizumab in advanced gastric and
gastroesophageal junction adenocarcinoma that has progressed on at least 2 lines of prior
therapy for advanced disease. Pembrolizumab has recently received FDA approval for PD-L1
positive gastric and GEJ adenocarcinoma based on the Keynote-059 study. The efficacy of
pembrolizumab monotherapy is modest in PD-L1 positive patients (defined as a combined
positive score, CPS, of > 1), with only a ~15% overall response rate. This study will examine
the addition of the oncolytic virus, OBP-301, administered prior to pembrolizumab in this
patient population. Patients will be enrolled in a two-stage design, with 18 patients in the
first stage. All patients will receive OBP-301 at 2x1012 viral particles (VP)/ tumor
injection administered every two weeks x 4 injections as well as standard dose pembrolizumab
200 mg IV every 3 weeks. The tumor will be injected with OBP-301 four times (d1, d15, d29,
d43). The preference is to inject the primary tumor endoscopically. Metastatic lesions may be
injected on a case-by-case basis after discussion with the PI (Shah). All patients treated
with OBP-301 will be eligible for the safety cohort.
Primary Endpoints:
- To examine the efficacy of OBP-301 with pembrolizumab in PD-L1 positive advanced gastric
and gastroesophageal junction adenocarcinoma in the 3rd or 4th line setting, as assessed
by the RECIST response rate.
- To examine the safety of multiple OBP-301 intratumoral injections in combination with
pembrolizumab in advanced gastroesophageal adenocarcinoma.
Secondary Endpoint:
• To examine other measures of efficacy of the combination of OBP-301 with pembrolizumab in
advanced gastric and esophageal adenocarcinoma including the disease control rate, duration
of response, overall survival and progression free survival.
Inclusion Criteria:
- Be willing and able to provide written informed consent for the trial.
- Be >18 years of age on the day of signing the informed consent.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Have histologically or cytologically confirmed advanced or metastatic gastroesophageal
adenocarcinoma, at least 1 cm in size and amenable to intratumoral injection.
- Patient must have received at least 2 line of systemic therapy for advanced disease.
- Tumor must be PD-L1 positive, as defined by a combined positive score (CPS).
- Have one or more measurable lesions based on iRECIST.
- Be willing to provide tissue; newly obtained biopsy specimens or formalin-fixed,
paraffin-embedded (FFPE) block specimens.
- Female subjects of childbearing potential have a negative urine or serum pregnancy
test within 7 days prior to enrollment. If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required. If a serum pregnancy
test is required it can be performed on the same day as the urine pregnancy test. The
serum pregnancy test must also be completed 7 days prior to enrollment. And male /
female subjects of childbearing potential must agree to use an adequate method of
contraception starting with signing the informed consent through 120 days after the
last dose of study medication.
- Demonstrated adequate organ function as defined in following criteria. All screening
labs should be performed within 14 days of enrollment. Note: Subject must not have
taken transfusion, hematopoietic agent; granulocyte-colony stimulating factor (GCSF)
etc., and/or oxygen supplementation within 7 days before the screening labs.
- Absolute neutrophil count (ANC)>1,000 /mm3
- Platelets>100,000 /mm3
- Hemoglobin>8.0 g/dL
- Serum total bilirubin<2.0 mg/dL
- Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT)< 3x
Upper limit of normal (ULN). For subjects with liver metastases< 5x ULN.
- Serum creatinine< 2.0 mg/dL; or if serum creatinine > 2.0 mg/dL, measured or
calculated creatinine/clearance >45 mL/min (Cockcroft-Gault formula).
- Life expectancy of ≥ 4 months from the first OBP-301 treatment.
- Understand the study requirements and the treatment procedures, and is willing to
comply with all specified follow-up evaluations, and provides written informed consent
before any study-specific tests or procedures are performed.
Exclusion Criteria:
- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy within 4 weeks of study Day 1.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (greater
than equivalent of prednisone 20 mg/day) or any other form of immune-suppressive
therapy within 7 days prior to study Day 1.
- Has known active central nervous system metastases and/or carcinomatous meningitis.
- Has had prior anti-cancer monoclonal antibody chemotherapy, targeted small molecule
therapy, or radiation therapy within 2 weeks prior to study Day 1, who has not
recovered from adverse events due to a previously administered agent.
- Has a known additional malignancy within 3 years of first injection of OBP-301 that is
progressing or requires active treatment, with the exception of prostate cancer
controlled with androgen deprivation therapy.
- Has received a live vaccine within 30 days of planned start of study therapy.
- Patients known to have acute or chronic active hepatitis B virus (HBV), hepatitis C
virus (HCV), or human immunodeficiency virus (HIV).
- Has any evidence of active, non-infectious pneumonitis or interstitial lung disease
requiring steroids.
- Has an active infection requiring systemic therapy within 2 weeks of Day 1.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.
- Previous severe hypersensitivity to another monoclonal antibody
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled
diabetes, ongoing or active infection, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/psychological
incompetence, whereby in the opinion of the Investigator the patient is assessed as
being unable to provide information, consent, or comply with the study requirements
and procedures.
- Patients who are pregnant or breastfeeding, or expecting to conceive or father
children within the projected timeframe of the study, starting from the time of the
Screening Visit through 4 months (120 days) after the last OBP-301 administration.
Females of childbearing potential must have a negative serum or urine pregnancy test
at Screening. A female not of childbearing potential is one who has undergone
bilateral oophorectomy or who has had no menses for 12 consecutive months.
