Esophageal Cancer, Esophageal Neoplasms, Esophageal Tumor, Esophagogastric Tumors, Gastric Cancer, Gastric Tumor, GastroEsophageal Cancer, Gastroesophageal Junction Adenocarcinoma, Gastroesophageal Junction Cancer, Gastroesophageal Junction Tumor
Conditions
Keywords
Esophagogastric Tumors, Esophagogastric Cancers, Gastric Cancer, Esophageal Cancer, Gastroesophageal Junction Cancer, GEJ Tumor, Pembrolizumab, Trastuzumab, 20-158, Memorial Sloan Kettering Cancer Center
Brief summary
The purpose of this study is to find out whether treatment with trastuzumab combined with pembrolizumab will improve the clearance of tumor DNA from participants' bodies after surgery.
Interventions
DRUGTrastuzumab
Trastuzumab (8mg/kg loading dose; 6mg/kg maintenance) will be administered on day 1 of each 3-week dosing cycle (21 days).
DRUGPembrolizumab
Pembrolizumab 200 mg IV will be administered on day 1 of each 3-week dosing cycle (21 days).
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single arm pilot study of adjuvant pembrolizumab + trastuzumab.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older. * ECOG performance status 0-2. * Sign informed consent within 8 months after curative surgery and completion of standard of care perioperative and/or adjuvant therapy. * HER2+ esophageal, GEJ, or gastric adenocarcinoma biopsy or resection specimen as defined by local HER2 IHC3+ or IHC 2+/FISH\>2.0 expression. * Must have genetic testing of DNA from primary tumor for somatic genomic alterations across a minimum of 50 genes. * Must have undergone a complete curative surgical resection (R0). * Must have completed standard of care (SOC) surgery, neoadjuvant or adjuvant therapy * CtDNA will be tested at a minimum of four weeks after completion of surgery and standard perioperative and/or adjuvant therapy. To be eligible for trastuzumab/pembrolizumab or trastuzumab therapy, the patients must have positive ctDNA (as defined in section 7.0) within 8 months after completion of appropriate standard of care therapy (surgery, chemotherapy, radiation as appropriate). For all patients, if the initial ctDNA has a negative result, ctDNA can be re-tested 4 weeks later, within 9 months of completion of standard therapy. * Demonstrate adequate organ function as defined in Table 1. Hematological Absolute neutrophil Count (ANC): ≥ 1,500 /mcL Platelets: ≥ 100,000 /mcL Hemoglobin: ≥ 9 g/dL Renal Serum creatinine ≤ 1.5 X upper limit of normal (ULN) Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN. Except patients with Gilbert's disease (≤ 3 x ULN) AST and ALT ≤ 2.5 X ULN Albumin ≥ 3 mg/dL
Exclusion criteria
* Patients who have not recovered from serious adverse events (as determined by treating MD) related to surgery. * Presence of metastatic or recurrent disease. * Had R1 (microscopic residual tumor) or R2 resection (macroscopic residual tumor at resection margin). * Left ventricular ejection fraction \<50% within 1 month of screening by MUGA or echocardiogram. * Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. * Has a 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. * Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT scan contrast premedication) may be enrolled. * The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. * Has a known history of active TB (Bacillus tuberculosis) * Hypersensitivity to pembrolizumab or any of its excipients. * Has had prior chemotherapy, targeted small molecule therapy, or radiation 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. ° Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has known history of, or any evidence of active, non-infectious pneumonitis. * Has an active infection requiring systemic therapy. * 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. * 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 pre-screening or screening visit through 120 days after the last dose of trial treatment. * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 agent. * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease; systemic lupus erythematosus; Wegener syndrome \[granulomatosis with polyangiitis\]; myasthenia gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: * Subjects with vitiligo or alopecia * Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment. * Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Has received a live vaccine within 30 days of planned start of study therapy. ° Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. * Is unwilling to give written informed consent, unwilling to participate, or unable to comply with the protocol for the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of ctDNA Clearance at 6 Months | 6 months | The primary endpoint of the study is the proportion of patients with ctDNA clearance at 6 months with trastuzumab/pembrolizumab or trastuzumab/placebo in patients with HER2+ esophagogastric cancer with persistent ctDNA despite curative surgery and standard perioperative/adjuvant therapy. CtDNA clearance is the conversion of detectable to undetectable ctDNA |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab and Pembrolizumab Trastuzumab will be administered on an every 3 week dosing schedule, with initial loading dose of 8 mg/kg as a 90 minute infusion, followed by trastuzumab 6 mg/kg every 3 weeks.
The planned dose of pembrolizumab for this study is 200 mg every 3 weeks.
Trastuzumab: Trastuzumab (8mg/kg loading dose; 6mg/kg maintenance) will be administered on day 1 of each 3-week dosing cycle (21 days).
Pembrolizumab: Pembrolizumab 200 mg IV will be administered on day 1 of each 3-week dosing cycle (21 days). | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Trastuzumab and Pembrolizumab |
|---|---|
| Age, Continuous | 86 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Rate of ctDNA Clearance at 6 Months
The primary endpoint of the study is the proportion of patients with ctDNA clearance at 6 months with trastuzumab/pembrolizumab or trastuzumab/placebo in patients with HER2+ esophagogastric cancer with persistent ctDNA despite curative surgery and standard perioperative/adjuvant therapy. CtDNA clearance is the conversion of detectable to undetectable ctDNA
Time frame: 6 months
Population: N/A - data were not collected because the one participant accrued to the study died prematurely due to a treatment unrelated infection