GB-5267 for the Treatment Platinum-Resistant Ovarian, Peritoneal, or Fallopian Tube Cancer

Inclusion Criteria

• At least 18 years of age at the time of signing informed consent
• Patients must have epithelial ovarian, peritoneal, or fallopian tube cancer that is confirmed by histology or cytology, with a histopathological diagnosis of serous, clear cell, endometrioid, mucinous carcinoma, or carcinosarcoma
• Must have platinum-resistant disease, defined as: * Progression of disease within 6 months of last platinum-based chemotherapy, OR * Patients who have an intolerance for further platinum-based therapy
• Cancer antigen (CA)125 > 2 x upper limit of normal (ULN) as assessed at the local lab by a 501(k) cleared test at screening. * Note: CA125 testing is performed to confirm evidence of active disease in the context of eligibility assessment. The assay is not intended as a companion diagnostic, predictive test, or for guiding clinical care outside of this study.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Must have evaluable disease or measurable disease defined as: * Measurable lesion as per RECIST v 1.1 criteria ** Note: Subjects undergoing tumor biopsies must have additional non-target lesions that can be biopsied at acceptable risk as judged by the investigator. If no other lesion is suitable for biopsy, then a target lesion used for biopsy must be ≥ 2 cm in longest diameter
• Absolute neutrophil count (ANC) ≥ 1,000/mm^3
• Platelet count ≥ 50,000/mm^3
• Hemoglobin ≥ 8.5 g/dL
• Adequate renal function, including estimated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault) or directly measured with a 24-hour urine collection test
• Total bilirubin ≤ 1.5 x ULN, except in subjects with Gilbert’s Syndrome who must have a total bilirubin ≤ 3 x ULN
• Aspartate and alanine aminotransferase (AST and ALT) ≤ 3 x ULN; ≤ 5 x ULN if there is liver involvement by the tumor
• Life expectancy of at least 3 months without treatment
• Participant must be willing to undergo core or excisional biopsy of a tumor lesion * A pretreatment biopsy must be obtained following completion of screening procedures and at least 7 days prior to the cell infusion. * An on-treatment biopsy must be performed on Day 28 (± 5 days) after infusion. * An end-of-treatment biopsy must be performed within 10 days of disease progression or any other reason for discontinuation. ** Note: Biopsies are expected to be obtained at pre-specified time points whenever feasible and safe; however, exceptions may be made if tumor tissue is inaccessible, a biopsy is deemed unsafe by the investigator, an attempted biopsy fails to yield adequate material, or in cases where tumor shrinkage limits availability
• Individuals of child-bearing potential (ICBP), defined as a sexually mature individual who has not undergone a hysterectomy, bilateral oophorectomy, or tubal ligation, or who has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months, * Must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test, as verified by the Investigator, at screening and baseline. * Must agree to abstain from breastfeeding during study participation and for at least 1 year post-GB-5267 infusion. * Must agree to use effective methods of contraception during sexual contact that has the possibility of resulting in pregnancy without interruption from the time of infusion until at least 1 year post GB-5267 infusion. Contraception methods must include 1 highly effective and 1 additional effective (barrier) method of contraception. ** Note: Highly effective methods are defined as those that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. The following are examples of highly effective and additional effective methods of contraception: *** Intrauterine device or system *** Hormonal (birth control pill, injections, implants) *** Tubal ligation *** Partner’s vasectomy
• Ability and willingness to adhere to the study visit schedule and all protocol requirements
• Participant must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria

• Coagulation abnormalities and hemorrhage: * Recent significant bleeding, defined as a history of grade ≥ 2 hemorrhage within 30 days before screening. * Coagulation parameters (assessed at screening): ** Activated partial thromboplastin time (aPTT) >1.5 × ULN. *** Exception: Participants on therapeutic heparin may be allowed if aPTT is between 1.5 and 2.5 × ULN. ** International Normalized Ratio (INR) > 1.5. *** Exception: Participants on warfarin are allowed if INR is between 2.0 and 3.0 on two consecutive measurements taken 1–4 days apart. ** Anticoagulant use: Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes is excluded. Prophylactic anticoagulation (e.g., low-molecular-weight heparin [LMWH] 40 mg/day) or use of anticoagulants for venous access device patency is permitted if the participant has been on a stable dose for ≥ 4 weeks without bleeding complications
• History or evidence of thrombotic or hemorrhagic disorders within 3 months prior to screening, including cerebrovascular accident (CVA) / stroke, transient ischemic attack (TIA), or subarachnoid hemorrhage
• Known history or presence of clinically relevant central nervous system (CNS) pathology (e.g., untreated or active brain metastases, epilepsy requiring ongoing treatment, stroke or subarachnoid hemorrhage within 3 months, severe neurodegenerative disorders, or psychosis)
• Active or clinically significant autoimmune disease requiring systemic immunosuppression (e.g., > 10 mg/day prednisone equivalent or other immunosuppressants) within the past 6 months. * Exception: Patients with stable, well-controlled autoimmune conditions, including but not limited to: ** Type 1 Diabetes Mellitus on stable insulin therapy ** Hypothyroidism managed with hormone replacement ** Vitiligo ** Resolved childhood asthma ** Patients on low-dose immunosuppressants (≤10 mg/day prednisone equivalent) without recent exacerbations ** Other non-systemic autoimmune conditions deemed low risk at the Principal Investigator’s (PI) discretion
• Any treatment-related immune-mediated adverse events (AEs) from previous immunotherapy that have not resolved to baseline or grade ≤ 1 at least 3 months prior to enrollment
• Ongoing systemic bacterial, viral, or fungal infection not improving despite appropriate antimicrobial therapy, or requiring intravenous (IV) antimicrobials at screening. Participants receiving prophylactic antimicrobials are eligible if there is no active infection
• Any other active malignancy within 2 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ (e.g., cervix, breast)
• Need for urgent intervention due to tumor mass effects (e.g., bowel obstruction or major vascular compression) that would preclude protocol compliance
• Cardiac-related exclusions: * History of Class III or IV congestive heart failure, non-ischemic cardiomyopathy, unstable or poorly controlled angina, or peripheral arterial disease event within 6 months prior to enrollment. * Echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) < 40%. * Previous myocardial infarction within 1 year prior to screening. * Clinically significant arrhythmia (e.g., second- or third-degree atrioventricular (AV) block, paroxysmal atrial fibrillation requiring active treatment, or prior pacemaker/defibrillator placement). * Any history of myocarditis. * Signs or symptoms of active angina, arrhythmia, or heart failure. Moderate-to-severe valvular disease not surgically corrected is also excluded. * Baseline plasma troponin-T above institutional ULN. ** Exception: Minimally elevated troponin-T is permitted if cleared by a cardiologist. * Inadequately controlled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg). * Known history of hypertensive crisis or hypertensive encephalopathy. * Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, recent peripheral arterial thrombosis) within 6 months prior to enrollment. * Pericardial involvement in the primary ovarian malignancy
• Pulmonary and third-space fluid: * Oxygen saturation < 92% on room air. * Known history or evidence of interstitial lung disease (ILD) or active, noninfectious pneumonitis within the past 5 years. * Clinically significant third-space fluid (pericardial, pleural, or peritoneal) requiring recurrent drainage, or fluid drained for symptom management within 28 days prior to screening
• Any serious, uncontrolled medical condition (e.g., cirrhotic liver disease, recent significant trauma, or severe psychiatric illness) that, in the opinion of the Investigator, could compromise participant safety or the interpretation of study data
• Prior or concurrent therapies: * Treatment with any previous anti-MUC16 therapy. * Prior allogenic stem cell transplant. * Receipt of any cellular or gene therapy. * Prohibited medications relative to leukapheresis or study treatment: ** Steroids: Therapeutic doses (> 10 mg/day prednisone equivalent) within 72 hours prior to leukapheresis/GB-5267 infusion; physiologic replacement doses and topical/inhaled steroids are allowed. ** Immunosuppressants: Any non-steroidal immunosuppressive medications (e.g., cyclosporine, biologic TNF inhibitors) within 2 weeks prior to leukapheresis. ** Antiproliferative therapies: Within 2 weeks prior to leukapheresis. ** Radiation therapy: Within 2 weeks prior to leukapheresis
• Live vaccine administration: * Receipt of a live vaccine within 30 days prior to enrollment
• Infectious disease (HIV, hepatitis): * Known HIV positivity (unless otherwise specified in the protocol for well controlled HIV). * Active or inadequately controlled hepatitis A, B, or C infection: ** Hepatitis A: Positive anti-hepatitis A virus (HAV) IgM excludes participation; positive antiHAV IgG alone is allowed. ** Hepatitis B: Vaccinated individuals (positive hepatitis B surface antigen [HBsAb] only) are eligible. Past exposure (Hepatitis B virus core antibody [HBcAb] positive) is permitted if the participant has undetectable hepatitis B virus (HBV) deoxyribonucleic acid (DNA) for ≥ 6 months and is on or has completed antiviral prophylaxis. ** Hepatitis C: Participants with positive anti-hepatitis C virus (HCV) antibody must have undetectable HCV ribonucleic acid (RNA) (polymerase chain reaction [PCR]) for ≥ 6 months. ** Participants who are hepatitis antibody–positive but DNA/RNA–negative (e.g., due to recent intravenous immunoglobulin [IVIG]) may be allowed at Investigator discretion