Patient eligibility
vitiligo, rheumatoid arthritis, tumor, arrhythmia, HIV, hepatitis B virus, ICH, toxicities, allergic reactions, cancer, edema, serous, lupus, Toxicity, cardiac disease, carcinoma of the cervix, liver cirrhosis, infection, Active infection, prostate cancer, allogeneic hematopoietic stem cell transplant, MPM, autoimmune or immune-mediated disease, serous ovarian adenocarcinoma, alcohol abuse, intercurrent illness, breast, stage 0 or 1 melanoma, NSCLC.Tumor, alopecia, unresectable disease, cholangiocarcinoma
VITILIGO, RHEUMATOID ARTHRITIS, TUMOR, IMMUNOSUPPRESSION, CARCINOMATOUS MENINGITIS, ARRHYTHMIA, INFLAMMATORY BOWEL DISEASE, STERILE, MULTIPLE SCLEROSIS, ACUTE CORONARY SYNDROME, HEART, SMALL VESSEL VASCULITIS, SEVERE ACUTE RESPIRATORY SYNDROME, ALLERGIC REACTION, DEEP VEIN THROMBOSIS, CANCER, EDEMA, PERICARDIAL EFFUSION, REMISSION, LUPUS, CARDIAC DISEASE, CNS METASTASES, CORONAVIRUS, SQUAMOUS CELL CARCINOMA, CARCINOMA OF THE CERVIX, INTERSTITIAL LUNG DISEASE, PRIMARY SCLEROSING CHOLANGITIS, INFLUENZA, LEPTOMENINGEAL DISEASE, BRAIN METASTASES, MINOR, PERITONEAL CANCER, LIVER CIRRHOSIS, MALIGNANCIES, INFECTION, CONGESTIVE HEART FAILURE, HEPATITIS C, METASTASES, PROSTATE CANCER, COVID-19 (CORONAVIRUS DISEASE 2019), VIRUS, FALLOPIAN TUBE, DISEASE, ALOPECIA, PERIPHERAL NEUROPATHY, CHOLANGIOCARCINOMA
Eligibility for the study required that patients met all of the following criteria:Voluntarily agreed to participate by giving written informed consent in accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and applicable local regulations.Agreement to abide by all protocol-required procedures, including study-related assessments, and management by the treating institution for the duration of the study and long-term follow-up.Age ≥18 years at the time the informed consent is signed.Pathologically confirmed diagnosis of MPM, serous ovarian adenocarcinoma (patients with serous fallopian tube or primary peritoneal cancers were also eligible), cholangiocarcinoma or NSCLC.Tumor was pathologically reviewed at a sponsor-designated central laboratory with confirmed positive mesothelin expression on ≥50% of tumor cells with 2+ and/or 3+ staining intensity by IHC. A fresh biopsy for confirmation of mesothelin expression was required at baseline (if not done at pre-screening) before gavo-cel administration.Patient had advanced (that is, metastatic or unresectable) cancer.Patient had at least one lesion that met evaluable and measurable criteria defined by RECIST version 1.1.Before gavo-cel infusion, patients must have received at least one systemic standard of care therapy for metastatic or unresectable disease and have failed FDA-approved agents for their disease (for example, PARP inhibitors for ECOG performance status 0 or 1.Negative rapid influenza diagnostic test and/or a respiratory viral panel (as per institutional guidelines) within 14 d before the planned gavo-cel infusion. Respiratory viral panel should be performed according to institutional guidelines and include Coronavirus Disease 2019 (COVID-19; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)). If the patient was symptomatic or tested positive, the gavo-cel infusion was delayed until the patient was asymptomatic and deemed fit for infusion by the treating physician.Left ventricular ejection fraction ≥45% as measured by resting echocardiogram, with no clinically significant pericardial effusion.Females of childbearing potential (FCBPs) must have a negative urine or serum pregnancy test (FCBP is defined as premenopausal and not surgically sterilized). FCBPs must agree to use effective birth control or to abstain from heterosexual activity throughout the study, starting on the day of first dose of lymphodepleting chemotherapy through 12 months after gavo-cel infusion or for 4 months after there is no evidence of persistence of gene-modified cells in the blood, whichever is longer. Effective contraceptive methods include intra-uterine device, oral or injectable hormonal contraception or two adequate barrier methods (for example, diaphragm with spermicide, cervical cap with spermicide or female condom with spermicide). Spermicides alone are not an adequate method of contraception. Male patients must be surgically sterile or agree to use a double-barrier contraception method or abstain from heterosexual activity with an FCBP starting at the first dose of protocol-defined treatment and for 4 months thereafter or longer (if indicated in the country-specific monograph/label for cyclophosphamide).Patient must have adequate organ function according to the following laboratory values:Patients meeting any of the following criteria were not eligible for participation in the study:Inability to follow the study procedures.Known or suspected non-compliance or drug or alcohol abuse.Participation in another study with investigational drug within the 28 d or 5 half-lives of the drug, whichever is shorter, preceding and during the present study.Patient is pregnant (or intends to become pregnant during the course of the study) or breastfeeding.Patient has received the following treatment before initiating protocol-defined therapy with either LD or gavo-cel:Cytotoxic chemotherapy within 3 weeks of gavo-cel infusion.Corticosteroids: therapeutic doses of steroids must be stopped at least 2 weeks before gavo-cel infusion. Inhaled corticosteroids are not exclusionary.Immunosuppression: any other immunosuppressive drugs (for example, methotrexate and mycophenolate) must be stopped ≥4 weeks before the first protocol-defined treatment.Use of an anti-cancer vaccine within 2 months in the absence of tumor response or 6 months if responding.Any previous gene therapy using an integrating vector.Tyrosine kinase inhibitors within 72 h.Any previous allogeneic hematopoietic stem cell transplant.Investigational treatment or clinical trial within 4 weeks or 5 half-lives of investigational product, whichever is shorter.Radiotherapy to the target lesions within 3 months before lymphodepleting chemotherapy unless palliative radiotherapy to non-targeted lesions.Current anti-coagulative therapy (excluding deep vein thrombosis prophylaxis).Immunotherapy (monoclonal antibody therapy and checkpoint inhibitors) within 4 weeks.Toxicity from previous anti-cancer therapy that had not recovered to ≤grade 1 (except for non-clinically significant toxicities—for example, alopecia and vitiligo). Grade 2 toxicities that are deemed stable or irreversible (for example, peripheral neuropathy) are non-exclusionary.History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.History of autoimmune or immune-mediated disease, such as multiple sclerosis, lupus, rheumatoid arthritis, inflammatory bowel disease or small vessel vasculitis.Major surgery (other than diagnostic surgery) within 4 weeks before the first protocol-defined therapy and minor surgery, including diagnostic surgery, within 2 weeks (14 d), excluding central intravenous port placements and needle aspirate/core biopsies. Radiofrequency ablation or transcatheter arterial chemoembolization within 6 weeks before enrollment.Leptomeningeal disease, carcinomatous meningitis or symptomatic central nervous system (CNS) metastases: patients are eligible if they have recovered from the acute effects of radiation therapy or surgery before study entry and (1) have no evidence of brain metastases after treatment or (2) are asymptomatic, have discontinued corticosteroid or anti-seizure therapy for metastases for at least 4 weeks and have radiographically stable CNS metastases (no growth, edema or shift for at least 3 months before study entry).Any other prior or concurrent malignancy, with the exception of treated basal cell or squamous cell carcinoma, in situ carcinoma of the cervix or breast, stage 0 or 1 melanoma completely resected more than 12 months before enrollment, successfully treated organ-confined prostate cancer and other malignancies completely resected and in remission for more than 5 years.Electrocardiogram showing a clinically significant abnormality at screening.Uncontrolled intercurrent illness, including active infection, clinically significant cardiac disease (for example, congestive heart failure New York Heart Association class 3 or class 4, significant arrhythmia and acute coronary syndrome), interstitial lung disease, liver cirrhosis or primary sclerosing cholangitis.Active infection with HIV, hepatitis B virus, hepatitis C virus or human T-lymphotropic virus.