Gastric Cancer, GastroEsophageal Cancer
Conditions
Brief summary
This study evaluates the combination of bavituximab and pembrolizumab in the treatment of gastric and gastroesphogeal cancer. All patients will receive both bavituximab, a drug that is not yet approved by the FDA, and pembrolizumab known as Keytruda. There is no expanded access program available for the investigational agents per this protocol.
Interventions
DRUGBavituximab
Bavituximab IV infusion
DRUGPembrolizumab Injection
Pembrolizumab IV Infusion
Sponsors
Merck Sharp & Dohme LLC
OncXerna Theraputics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent * Men and women ≥ 18 years old; ≥ 20 years old in South Korea and Taiwan * Unresectable metastatic or locally advanced gastric or GEJ adenocarcinoma * Progressed on and/or after at least 1 prior regimen for metastatic disease or achieved stable disease or better in two consecutive scans to PD-1/PD-L1 inhibition alone or in combination with chemotherapy and relapsed * Willing and able to provide fresh formalin-fixed paraffin-embedded tissue tumor sample * Presence of at least one measurable lesion * ECOG of 0 or 1 * Has adequate organ functions * Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to start of study treatment. * Women must not be breastfeeding. * Women of childbearing potential , must agree to follow instructions for highly effective method(s) of contraception * Males who are sexually active with women of childbearing potential must agree to follow instructions for highly effective method(s) of contraception * Has adequate treatment washout period before start of study treatment
Exclusion criteria
* Received any form of anti-phosphatidylserine therapies * Prior treatment with any checkpoint inhibitor or other therapies targeting T-cell control * Known microsatellite instability-high (MSI-H) gastric or GEJ adenocarcinoma * Medical history of myocardial infarction within 6 months before registration, symptomatic congestive heart failure (CHF) , troponin levels consistent with myocardial infarction, unstable angina, or serious cardiac arrhythmia * Weight loss \>10% over 2 months prior to first dose of study treatment * History of pneumonitis that required steroids or has current pneumonitis * Has known active CNS metastases/and or carcinomatous meningitis * Known additional malignancy that is progressing or has required active treatment in within the past 3 years * An active infection requiring systemic therapy * Known human immunodeficiency virus (HIV) infection or known acute hepatitis B or C infection * Unresolved toxicities from previous cancer treatments * History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator * Active autoimmune disease or history of chronic recurrent autoimmune disease * Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients. * History of infusion reactions to any component/excipient of bavituximab * History of severe hypersensitivity reactions to mAbs. * Systemic steroid therapy within 7 days prior to the first dose of study treatment * Has received a live vaccine within 30 days prior to first dose of study drug. * Prior organ transplantation including allogeneic or autologous stem-cell transplantation * Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment * Receipt of treatment with immunotherapy, biological therapies, or therapeutic doses of hormonal therapies within 3 weeks of scheduled C1D1 dosing * Known psychiatric, substance abuse disorder, or geographical travel limitations that would interfere with participant's ability to cooperate with the requirements of the study * Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment Emergent Adverse Events (TEAE) | From first dose through 30 days after last dose. Maximum exposure: 567 days. | Incidence of TEAEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, including changes in clinical laboratory parameters. TEAEs: any AE that emerged on or after first dose, and within 30 days of the last dose. |
| Severity of Treatment Emergent Adverse Events (TEAE) | From first dose through 30 days after last dose. Maximum exposure: 567 days. | Severity of TEAEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, including changes in clinical laboratory parameters. TEAEs: any AE that emerged on or after first dose, and within 30 days of the last dose. |
| Objective Response Rate (ORR) | From date of first dose until the date of CR, PR, first documented progression or date of death from any cause, whichever came first. Maximum exposure: 567 days. | ORR was based on RECIST version 1.1 criteria for target lesions, where a patient may achieve as best overall response (BOR) either complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline summary of diameters. ORR is calculated as the number of patients achieving a CR or PR (objective response) divided by the number of efficacy patients. |
Countries
South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 25 centers located in 4 countries. A total of 107 participants were screened between 11 September 2019 and 03 June 2021, out of which 80 participants enrolled in the study.
Pre-assignment details
A total of 80 participants received treatment: 61 participants had progressed on standard chemotherapy and were naïve to checkpoint inhibitor (CPI) therapy (CPI Naïve; Group 1) and 19 participants had achieved stable disease (SD) or better and then subsequently progressed following treatment with CPI either alone or in combination with chemotherapy (CPI Relapse; Group 2). Data are reported based on the date of 20 December 2021.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (CPI Naïve) Group 1 participants had progressed on standard chemotherapy and were naïve to CPI therapy.
Participants received bavituximab at 3 mg/kg on Days 1, 8, and 15 of a 3-week cycle through IV infusion. Participants received pembrolizumab at 200 mg on Day 1 of a 3-week cycle through IV infusion. | 61 |
| Group 2 (CPI Relapse) Group 2 participants had achieved SD or better and then subsequently progressed following treatment with CPI either alone or in combination with chemotherapy.
Participants received bavituximab at 3 mg/kg on Days 1, 8, and 15 of a 3-week cycle through IV infusion. Participants received pembrolizumab at 200 mg on Day 1 of a 3-week cycle through IV infusion. | 19 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 46 | 12 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Group 2 (CPI Relapse) | Group 1 (CPI Naïve) | Total |
|---|---|---|---|
| Age, Continuous | 61.2 years STANDARD_DEVIATION 11.68 | 60.2 years STANDARD_DEVIATION 12.82 | 60.4 years STANDARD_DEVIATION 12.49 |
| Central PD-L1 Combined Positive Score <1 | 7 Participants | 17 Participants | 24 Participants |
| Central PD-L1 Combined Positive Score ≥10 | 5 Participants | 18 Participants | 23 Participants |
| Central PD-L1 Combined Positive Score ≥1 and <10 | 4 Participants | 22 Participants | 26 Participants |
| Central PD-L1 Combined Positive Score Missing | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 55 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 33 Participants | 45 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) White | 4 Participants | 21 Participants | 25 Participants |
| Region of Enrollment South Korea | 12 Participants | 21 Participants | 33 Participants |
| Region of Enrollment Taiwan | 0 Participants | 11 Participants | 11 Participants |
| Region of Enrollment United Kingdom | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 4 Participants | 27 Participants | 31 Participants |
| Sex: Female, Male Female | 4 Participants | 16 Participants | 20 Participants |
| Sex: Female, Male Male | 15 Participants | 45 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 46 / 61 | 12 / 19 |
| other Total, other adverse events | 61 / 61 | 19 / 19 |
| serious Total, serious adverse events | 29 / 61 | 10 / 19 |
Outcome results
Primary
Number of Patients With Treatment Emergent Adverse Events (TEAE)
Incidence of TEAEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, including changes in clinical laboratory parameters. TEAEs: any AE that emerged on or after first dose, and within 30 days of the last dose.
Time frame: From first dose through 30 days after last dose. Maximum exposure: 567 days.
Population: Analysis was performed on the safety population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (CPI Naïve) | Number of Patients With Treatment Emergent Adverse Events (TEAE) | 61 Participants |
| Group 2 (CPI Relapse) | Number of Patients With Treatment Emergent Adverse Events (TEAE) | 19 Participants |
Primary
Objective Response Rate (ORR)
ORR was based on RECIST version 1.1 criteria for target lesions, where a patient may achieve as best overall response (BOR) either complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline summary of diameters. ORR is calculated as the number of patients achieving a CR or PR (objective response) divided by the number of efficacy patients.
Time frame: From date of first dose until the date of CR, PR, first documented progression or date of death from any cause, whichever came first. Maximum exposure: 567 days.
Population: The efficacy population include all participants enrolled in the study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 (CPI Naïve) | Objective Response Rate (ORR) | Partial Response | 6 Participants |
| Group 1 (CPI Naïve) | Objective Response Rate (ORR) | Progressive Disease | 31 Participants |
| Group 1 (CPI Naïve) | Objective Response Rate (ORR) | Stable Disease | 16 Participants |
| Group 1 (CPI Naïve) | Objective Response Rate (ORR) | Not Evaluable | 6 Participants |
| Group 1 (CPI Naïve) | Objective Response Rate (ORR) | Complete Response | 2 Participants |
| Group 2 (CPI Relapse) | Objective Response Rate (ORR) | Not Evaluable | 1 Participants |
| Group 2 (CPI Relapse) | Objective Response Rate (ORR) | Complete Response | 0 Participants |
| Group 2 (CPI Relapse) | Objective Response Rate (ORR) | Partial Response | 1 Participants |
| Group 2 (CPI Relapse) | Objective Response Rate (ORR) | Stable Disease | 9 Participants |
| Group 2 (CPI Relapse) | Objective Response Rate (ORR) | Progressive Disease | 8 Participants |
Primary
Severity of Treatment Emergent Adverse Events (TEAE)
Severity of TEAEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, including changes in clinical laboratory parameters. TEAEs: any AE that emerged on or after first dose, and within 30 days of the last dose.
Time frame: From first dose through 30 days after last dose. Maximum exposure: 567 days.
Population: Analysis was performed on the safety population.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 (CPI Naïve) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 2 TEAE | 19 Participants |
| Group 1 (CPI Naïve) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 4 TEAE | 1 Participants |
| Group 1 (CPI Naïve) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 3 TEAE | 21 Participants |
| Group 1 (CPI Naïve) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 5 TEAE | 17 Participants |
| Group 1 (CPI Naïve) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 1 TEAE | 3 Participants |
| Group 2 (CPI Relapse) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 5 TEAE | 5 Participants |
| Group 2 (CPI Relapse) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 1 TEAE | 4 Participants |
| Group 2 (CPI Relapse) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 2 TEAE | 2 Participants |
| Group 2 (CPI Relapse) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 3 TEAE | 8 Participants |
| Group 2 (CPI Relapse) | Severity of Treatment Emergent Adverse Events (TEAE) | At least one Grade 4 TEAE | 0 Participants |