A Study to investigate Bavituximab in combination with Pembrolizumab in patients with advanced gastric or gastroesophageal cancer.

Phase 1

Active, not recruiting

• Conditions: Advanced gastric or gastroesophageal cancer that progressed on or after at least one prior standard therapy; MedDRA version: 21.0Level: LLTClassification code 10017760Term: Gastric cancer NOSSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10017767Term: Gastric cancer stage IV with metastasesSystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10017768Term: Gastric cancer stage IV without metastasesSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10066354Term: Adenocarcinoma of the gastroesophageal junctionSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000949-13-GB
• Lead Sponsor: OncXerna Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-07-30
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

For Group 1 only (CPI naïve):
1. Progressed on and/or after at least 1 prior regimen for metastatic disease which includes a fluoropyrimidine and a platinum:
• Progression within 6 months of prior adjuvant or neoadjuvant chemotherapy will be deemed a rapid progressor and thus, equivalent to 1 advanced/metastatic disease treatment regimen.
• Changing from IV to oral fluoropyrimidine without noted progression is considered only 1 prior regimen.
• Human epidermal growth factor receptor 2 (HER2)-positive patients must have received prior anti-HER2 therapy and demonstrate PD or was ineligible for such therapy.

For Group 2 only (CPI relapse):
2. Patient achieved stable disease or better in two
consecutive scansachieved stable disease or better in two consecutive scans to PD-1/PD-L1 inhibition alone or in combination with chemotherapy and relapsed following PD-1/PD-L1 inhibition either alone or in combination with chemotherapy
• All patients must be immediate (defined by within 3 months) progressors of PD 1/PD-L1 inhbition with no intervening treatment with other agents such as chemotherapy alone.

For both Group 1 and Group 2:
3. Signed written informed consent obtained prior to performing any study procedure, including screening procedures.
4. Men and women = 18 years old; = 20 years old in South Korea and Taiwan.
5. Pathologically documented unresectable metastatic or locally advanced gastric or GEJ adenocarcinoma:
• Must be metastatic/unresectable at the time of enrollment into this study.
6. Willing and able to provide fresh (since most recent progression) formalin-fixed paraffin-embedded tissue tumor sample for screening of signature status prior to study treatment and to measure PD-1 status. An archival tissue sample should also be provided, if available.
7. Presence of at least one measurable lesion assessed by the Investigator per RECIST version 1.1.
8. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
9. Has adequate organ functions defined as listed in table in section 4.2 in the Protocol.
10. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to start of study treatment.
11. Women must not be breastfeeding.
12. Women of childbearing potential defined as not surgically sterile or have not been free from menses for = 2 years, must agree to follow instructions for highly effective method(s) of contraception. Patients or Partners of Patients of Reproductive Potential for the duration of treatment with study drug bavituximab and pembrolizumab plus 5 months post-treatment completion.
Males who are sexually active with women of childbearing potential must agree to follow instructions for highly effective method(s) of contraception or Partners of Patients of Reproductive Potentialfor the duration of treatment with study treatment plus 90 days post-treatment completion.
13. Has adequate treatment washout period before the start of study treatment, defined as:
• Major surgery = 4 weeks; radiation therapy with abdominal radiation = 4 weeks and have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.; palliative radiation without abdominal radiation, = 2 weeks; chemotherapy = 3weeks; biologic therapy = 3 weeks
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age ra

Exclusion Criteria

For Group 1 only (CPI naïve):
1. Prior treatment with any checkpoint inhibitor or other therapies targeting T-cell control.

For Group 2 only (CPI relapse):
2. Primary refractory patients, defined as disease progression at first scan following initiation of PD-1/PD-L1 inhibitor treatment, or if best overall response to PD 1/PD L1 inhibition was disease progression

For both Group 1 and Group 2:
3. Received any form of anti-phosphatidylserine therapies.
4. Known microsatellite instability-high (MSI-H) gastric or GEJ adenocarcinoma
5. Medical history of myocardial infarction within 6 months before registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV;), troponin levels consistent with myocardial infarction as defined according to American College of Cardiologists (ACC) guidelines, unstable angina, or serious cardiac arrhythmia requiring treatment.
6. Experienced weight loss >10% over 2 months prior to first dose of study treatment.
7. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
8. Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable without evidence of progression via imaging for at least four weeks prior to first dose of study, and no evidence of neurological symptoms. Carcinomatous meningitis is excluded regardless of clinical stability.
9. Known additional malignancy that is progressing or has required active treatment in within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
10. Active infection requiring systemic therapy.
11. Known human immunodeficiency virus (HIV) infection, or known acute hepatitis B or C infection.
12. Unresolved toxicities from previous cancer treatments (other than alopecia) not yet resolved to Grade = 1 or baseline. Grade 2 toxicities may be eligible at the discretion of the Investigator after consultation with the Sponsor’s medical monitor.
13. 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.
14. Active autoimmune disease or history of chronic recurrent autoimmune disease, requiring systemic treatment for the past two years (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Replacement therapy (thyroxine, insulin, or physiological corticosteroid replacement for either adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
15. Severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients.
16. History of infusion reactions to any component/excipient of bavituximab.
17. History of severe hypersensitivity reactions to mAbs.
18. Systemic steroid therapy (>10 mg daily prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment (note: topical, inhaled, nasal and ophthalmic steroids are permitted).
19. Received a live vaccine within 30 days prior to the first dose of study drug. Examp

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified