Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

80 mg/m\^2 intravenous Paclitaxel and intraperitoneal (IP) tgDCC-E1A starting dose 1.8 mg DNA/m\^2 weekly for six treatments every 7 days.

Weekly single agent intravenous Paclitaxel 80 mg/m\^2 for six treatments every 7 days.

Starting Dose Level: 1.8 mg DNA/m\^2 intraperitoneal every 7 days +/- 2 days for a total of 6 treatments each cycle.

Intraperitoneal tgDCC-E1A

80 mg/m\^2 intravenous (IV) every 7 days +/- 2 days for a total of 6 treatments.

Naoto Ueno, MD, PHD

The goal of this clinical research study is to find the highest safe dose of intraperitoneal tgDCC-E1A that can be given in combination with paclitaxel as a treatment for patients with recurrent, platinum-resistant ovarian cancer. How the cancer responds to this treatment will also be studied. Researchers will also ask the patients if they will allow additional tumor samples to be collected and extra blood samples to be drawn. These samples will be used to learn about the biological response before and after treatment.

Primary Objective

* To evaluate toxicity and establish the maximum tolerated dose (MTD) of intraperitoneal tgDCC-E1A in combination with intravenous paclitaxel.
* To measure tumor response of intraperitoneal tgDCC-E1A in combination with intravenous paclitaxel and compare to intravenous paclitaxel

Secondary Objective

* To measure time to progression and overall survival.
* To examine the biological effects of combined tgDCC- E1A and paclitaxel in ovarian cancer cells as measured by laboratory testing.

Epithelial ovarian cancer is a significant public health problem. It is the sixth most common cancer in women worldwide. Globally, it is estimated that 162,000 new cases are diagnosed per year, and that 106,000 women die from the disease per year.

Signs and symptoms of ovarian cancer are often subtle. Seventy-five percent of subjects will present with advanced stage III and IV disease. Standard treatment for stage III/IV subjects consists of surgical debulking to the maximal extent possible and chemotherapy with paclitaxel plus a platinum compound (cisplatin or carboplatin). Despite high initial response rates, the overall survival for this group is poor, with only 20% of stage III and less than 5% of stage IV subjects surviving five years.

Treatment of recurrent ovarian cancer varies depending upon the interval between prior treatment and recurrence. Twenty percent of subjects are classified as "platinum-refractory", in that they fail to have even a partial response to a platinum-containing regimen. Subjects with recurrent or progressive disease less than six months after initial therapy have a poor response rate to repeat treatment with a platinum-containing regimen, and are generally considered to have "platinum-resistant" disease. In contrast, subjects with recurrent disease greater than six months after initial therapy have better response rates to repeat treatment with platinum-containing regimens, and are generally considered to have "platinum-sensitive" disease.

There is no consensus for the treatment of "platinum-refractory" or "platinum-resistant" ovarian cancer, a class of individuals who are particularly challenging to treat. Prognosis is poor, and treatment is primarily palliative in nature. Responses to a variety of single chemotherapeutic agents, as well as to a combination of agents in largely phase II trials have been similar, ranging from 10-35%. Intravenous (IV) paclitaxel, given alone or in combination with other agents is a standard treatment for subjects who have relapsed. In an attempt to increase the dose intensity of paclitaxel therapy, weekly IV paclitaxel has been recommended. This treatment schedule is well tolerated, but the response rate in heavily pretreated subjects is still only 28.9%.

Given that this group of subjects is poorly responsive to conventional chemotherapy, and consequently has limited options, an alternative approach to treatment is warranted. The use of a gene therapy agent with anti-tumor effects and the ability to sensitize cancer cells to traditional chemotherapy is appealing.

* Overview of the Effect of E1A Gene Transfer on Cancer Cells:

E1A, a gene derived from Adenovirus type 5, has been shown to have potent anti-neoplastic activity through a variety of mechanisms, including down-regulation of HER-2/neu overexpression, induction of apoptosis, inhibition of metastasis, and reversion of tumor cells toward a differentiated epithelial phenotype. The E1A gene has also been shown to have an additive effect in vitro and in vivo on the apoptosis induced by chemotherapy and radiotherapy. The E1A gene has been successfully transfected into human cells both in vitro and in vivo using tgDCC-E1A (E1A-Lipid Complex), which consists of the E1A plasmid (pE1A-K2) complexed to the cationic lipid gene delivery system comprised of DC-Cholesterol 3b\[N-(N'N'-dimethylaminoethane)-carbamoyl\] cholesterol hydrochloride and DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine).

* Rationale for Use of Cationic Lipids to Deliver DNA:

Cationic lipids can form complexes with negatively charged DNA plasmids and facilitate the transfer of genes to target cells. They are useful agents for delivery of gene therapy because they are synthesized chemically, are simple to manufacture, and pose no infectious risk. The cationic derivative of cholesterol, 3b\[N-(N'N'-dimethylaminoethane)-carbamoyl\] cholesterol hydrochloride (DC-Chol) is an ideal cationic lipid for therapeutic use, as the cationic charge is provided by a non-toxic tertiary amine with a biodegradable carbamoyl bond. DC-Chol can be used to prepare liposomes in combination with the neutral 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) with a DC-Chol to DOPE ratio of 6:4. This liposome combination can be mixed with a plasmid encoding E1A to form tgDCC-E1A.

The final preparation of tgDCC-E1A can be made within a range of lipid:DNA ratios, all of which have been shown in cell culture and in animal models to result in expression of E1A. Clinical trials of tgDCC-E1A for injection into solid tumors have used a final preparation with a lipid:DNA ratio of 1 nmol lipid to 1 microgram DNA \[tgDCC-E1A (1:1)\]. Early clinical trials evaluating intracavitary administration (e.g. intraperitoneal infusion for ovarian cancer) used a preparation with a lipid:DNA ratio of 10 nmol lipid to 1 microgram DNA \[tgDCC-E1A (10:1)\]. More recent protocols of intraperitoneal delivery for ovarian cancer have used a preparation with a lipid:DNA ratio of 3 nmol lipid to 1 microgram DNA \[tgDCC-E1A (3:1)\], as will this protocol.

* Rationale for Intraperitoneal Delivery of tgDCC-E1A:

The peritoneal cavity is a common site of tumor recurrence after initial "radical" surgical treatment of ovarian malignancies. Dissemination in this cavity is often widespread. Because of the unusual natural course of ovarian cancer (characterized by its tendency to be confined to the peritoneal cavity), control of metastatic disease in the peritoneal cavity is an important and challenging problem, which can be improved by direct delivery of drug into the peritoneal cavity.

Intraperitoneal tgDCC-E1 and Intravenous Paclitaxel in Women With Platinum-Resistant Ovarian Cancer

Phase I of Phase I/II Randomized Study of Intraperitoneal tgDCC-E1 and Intravenous Paclitaxel in Women With Platinum-Resistant Ovarian Cancer

Dose combinations assigned using the Continuous Reassessment Method (CRM) with up to 8 cohorts of three subjects each assigned to one of the three tgDCC-E1A dose combinations (1.8 , 3.6 or 5.0 mg DNA/m\^2). Three weeks after third subject started treatment, the number of subjects who experienced dose limiting toxicities (DLT) tabulated. The next cohort of three subjects assigned to same or next higher dose combination using a computer algorithm that evaluates proportion of subjects who experienced a DLT.

Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response: disappearance all target \& non-target lesions, no evidence new lesions in 2 disease assessments 4 weeks apart; Partial Response (PR): \>30% decrease in sum longest dimensions (LD) of all target measurable lesions reference baseline sum of LD; 2 disease assessments 4 weeks apart required. IF ONLY target lesion is solitary pelvic mass measured by physical exam, not radiographically measurable, 50% decrease in LD required; Progressive disease (PD): \>20% increase in sum LD of target lesions references smallest sum LD or appearance new lesions. IF ONLY target lesion is solitary pelvic mass measured by physical exam, not radiographically measurable, 50% increase in LD required; Stable disease: neither sufficient shrinkage for PR nor increase for PD, reference smallest sum LD since treatment started, or IF non-target lesions persistence of 1+ non-target lesions and/or maintenance of tumor marker above normal limits.

National Institutes of Health (NIH)

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Specimen will be collected to prepare the iC9-CAR.B7-H3 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9-CAR.B7-H3 T cells. In part 2, the iC9-CAR.B7-H3 T cells are given by infusion after completion of lymphodepletion chemotherapy.

iC9-CAR.B7-H3 T cells will then be administered intravenously

iC9-CAR.B7-H3 T Cell Therapy

cyclophosphamide 300 mg/m2 IV will be given.

cyclophosphamide

fludarabine

Caroline Babinec

Catherine Cheng

E. Claire Dees, MD, MSc

Claire E Dees, MD, MSc

This phase 1, single-center, open-label study explores the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells in subjects with relapsed/refractory triple-negative breast cancer (TNBC).

T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (iC9-CAR.B7-H3 T cells) treatment is experimental and has not been approved by the Food and Drug Administration. The safety of iC9-CAR.B7-H3 T cells will be investigated using a modified 3+3 design. The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided based on the maximum tolerated dose (MTD) and additional factors such as the ability to manufacture sufficient cells for infusion.

Subjects with TNBC who meet procurement eligibility criteria will have cells collected to manufacture iC9-CAR.B7-H3 T cells. Eligible subjects will receive lymphodepletion with cyclophosphamide and fludarabine.

Study of Autologous CAR-T Cells Targeting B7-H3 in TNBC iC9-CAR.B7-H3 T Cells

Study of Administration of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors and Containing the Inducible Caspase 9 Safety Switch in Subjects With Triple Negative Breast Cancer

Toxicity will be graded as the Number of participants with adverse events (AE)s

AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild: Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38\^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death

Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria.

Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).

The RP2D of iC9-CAR.B7-H3 T cells will be determined based on modified 3+3 dose finding rules and the tolerability of iC9-CAR.B7-H3 T cells will be assessed by NCI-CTCAE v5 criteria.

The RP2D of iC9-CAR.B7-H3 T cells will be determined based on modified 3+3 dose finding rules and the tolerability of iC9-CAR.B7-H3 T cells will be assessed byASTCT Consensus CRS Grading Criteria.

The RP2D of iC9-CAR.B7-H3 T cells will be determined based on modified 3+3 dose finding rules and the tolerability of iC9-CAR.B7-H3 T cells will be assessed by ASTCT Consensus ICANS Grading Criteria.

Objective response rate is defined as the percentage of subjects achieving a confirmed partial response (PR) or better (≥ PR) based on RECIST 1.1 criteria.

Complete response - Disappearance of all target lesions. Any pathological lymph node (LN) must be \<10mm. Partial response: At least a 30% decrease in the sum of the largest distance (LD) of the target lesions. Progressive Disease (PD): At least a 20% increase in the sum of the LD of the target lesions taking as reference the smallest sum LD recorded since the treatment started including baseline if that is the smallest in the study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of one or more new lesions also constitutes PD. Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started.

PFS will be measured from the first day of lymphodepletion chemotherapy prior to iC9-CAR.B7-H3 T cell infusion to progression per RECIST 1.1 or death.

OS will be measured from the first day of lymphodepleting chemotherapy prior to iC9-CAR.B7-H3 T cell infusion to the date of death for any cause.

DOR is defined as the time from documentation of PR or better to progressive disease (PD) based on RECIST 1.1 and/or irRECIST.

Per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) for target and/or non-target lesions and assessed by imaging: Complete Response (irCR), Disappearance of all lesions, no new lesions, lymph nodes \< 10 mm in short axis; Partial Response (irPR), ≥30% decrease in the sum of target lesions and non-target lesions are irNN; Stable response (irSD), not meeting criteria for irCR, irPR, or irPD; Progressive Disease (irPD), ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir; for no new non-target or (irNN) and where irPR or irPD are confirmed by a repeat, consecutive assessment no less than 4 weeks later.

Bellicum Pharmaceuticals

UNC Lineberger Comprehensive Cancer Center

Blood and Lymph Conditions

Infections

Immune System Diseases

Leukemia

Pseudomonas Infections

Leukemia, Hairy Cell

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hairy Cell Leukemia

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Protective Agents

Immunotoxins

Immunotoxin HA22

Immunoconjugates

Patients will receive Moxetumomab Pasudotox intravenously (IV) over 30 minutes on days 1, 3, 5 of each 28 day cycle for a maximum of 6 cycles or until disease progression, unacceptable toxivity, initiation of alternate therapy or documented CR.

Moxetumomab pasudotox

IV Bag Protectant for Moxetumomab pasudotox

MedImmune LLC

Background:

- Moxetumomab pasudotox is an experimental non-chemotherapy cancer treatment drug. It targets CD22, a molecule on the surface of essentially all hairy cell leukemia cells. Moxetumomab pasudotox binds to CD22, goes into the cell, and releases a toxin which kills the cell. In a phase I trial it had activity in relapsed/refractory hairy cell leukemia with safety profile supporting further clinical study (http://ncbi.nlm.nih.gov/pubmed/22355053). This is a phase III multicenter trial designed to confirm these results.

Background:

* Hairy cell leukemia (HCL) is an indolent B-cell leukemia comprising 2% of all leukemias, or approximately 900 of the 44,000 new cases of leukemia/year in the US
* Over the last two decades, immunotoxin research has accumulated to support a role for CD22-targeted therapy in the treatment of HCL.
* Moxetumomab pasudotox is a recombinant immunotoxin containing an Fv fragment of an anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin.
* Moxetumomab pasudotox has demonstrated a high complete response (CR) rate in patients with chemoresistant HCL and has shown activity in pediatric acute lymphoblastic leukemia as well.
* Modification of the structure of moxetumomab pasudotox has greatly improved binding and cytotoxicity toward CD22 expressing malignant cells compared to the precursor molecule. Preclinical and clinical studies have demonstrated that this increase in binding affinity results in improved antitumor activity and tolerability
* Currently there are no approved agents with significant efficacy for HCL patients after failure of standard therapy

Design:

* This is a multicenter, single-arm study of moxetumomab pasudotox in patients with relapsed/refractory hairy cell leukemia.
* 77 patients will be enrolled to receive moxetumomab pasudotox intravenously (IV) on days 1, 3 and 5 of each 28 day cycle for a maximum of 6 cycles or until disease progression, unacceptable toxicity occurs, the subject begins alternate therapy, or documented CR (for subjects who have no assessable minimal residual disease and not to exceed 6 cycles). If less than or equal to 2 of the first 25 patients do not achieve durable CR, no additional patients will be accrued.
* The overall IRB accrual ceiling is currently set at 80 to allow for a small number of patients that cannot be assessed for response.

Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

A Pivotal Multicenter Trial of Moxetumomab Pasudotox in Relapsed/ Refractory Hairy Cell Leukemia

Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a \>180 day duration of hematologic remission (HR). CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either \< 17 cm or have decreased by \>25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a \>180 day duration of HR. CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either \< 17 cm or have decreased by \>25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

The MRD status by blinded independent review refers specifically to results of central pathologist read of bone marrow biopsy by immunohistochemistry.

The CR with Positive or Negative MRD requires all of the following to be present:

* No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or in bone marrow biopsy by immunohistochemistry.
* Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either \< 17 cm or have decreased by \>25% from its baseline.
* Normal CBC as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

The MRD status by investigator refers to results of investigator assessment of bone marrow biopsy or bone marrow aspirate by immunohistochemistry and/or flow cytometry.

The CR with Positive or Negative MRD requires all of the following to be present:

* No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or marrow by flow cytometry.
* Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either \< 17 cm or have decreased by \>25% from its baseline.
* Normal CBC as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Time to CR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of CR.

Duration of CR was defined as the duration from documentation of CR to the time of relapse from CR. Relapse from CR was defined as any CR criteria (blood counts, imaging or bone marrow) no longer consistent with CR. CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either \< 17 cm or have decreased by \>25% from its baseline); normal CBC as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Duration of HR was defined as the duration from documentation of HR to the time of relapse. HR was defined as the blood counts required for CR as normal CBC as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Duration of HR was censored on the date of the last hematologic assessment for participants who have no documented relapse based on blood count prior to data cutoff, dropout, or initiation of alternative anticancer therapy.

Time to HR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of HR. HR was defined as the blood counts required for CR as normal CBC as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

The OR was defined as number of participants with a best response of CR or PR. CR requires all of following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (\>=2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either \<17 cm or have decreased by \>25% from its baseline); normal CBC (Neutrophils \>=1.5 x 10\^9/L, Platelets \>=100 x 10\^9/L, and hemoglobin \>=11.0 g/dL) without transfusions or growth factors for at least 4 weeks. PR requires all of following for a period of at least 4 weeks: \>=50% decrease or normalization (\<5.0 x 10\^9/L) in peripheral blood lymphocyte count and \>=50% reduction in lymphadenopathy and in abnormal haepatosplenomegaly by CT or MRI from pre-treatment baseline value; normal CBC as mentioned above or 50% improvement in CBC values over baseline without transfusions or growth factors for at least 4 weeks.

Time to OR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of OR (CR or PR).

Duration of OR was defined as the time from the first documentation of objective response (CR or PR) to the date of relapse.

Duration of OR was censored on the date of last disease assessment or hematologic assessment for participants who have no documented relapse prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.

The PFS was defined as the time from the start of moxetumomab pasudotox administration to the earliest date of a disease assessment showing a progressive disease/relapse, earliest date of hematologic relapse or date of death, whichever was earlier. The PFS was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.

The TTF was defined as the time from the start of moxetumomab pasudotox administration to the date of the first of relapse, progressive disease, initiation of alternative anticancer therapy, or death due to disease or disease-related complication. The TTF was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy and also censored for death not accompanied by relapse.

An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug.

An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).

An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).

An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).

The Tmax of moxetumomab pasudotox is reported.

The Cmax of moxetumomab pasudotox is reported.

The Tlast of moxetumomab pasudotox is reported.

The AUC0-last of moxetumomab pasudotox is reported.

The AUC0-3hr of moxetumomab pasudotox is reported.

The AUC0-inf of moxetumomab pasudotox is reported.

The AUCExt of moxetumomab pasudotox is reported.

The CL of moxetumomab pasudotox is reported.

The t1/2 of moxetumomab pasudotox is reported.

Participants with ADA positive, nAb positive, cluster of differentiation 22 (CD22) positive of ADA positive/NAb positive, and pseudomonas exotoxin 38 (PE38) positive of ADA positive/NAb positive to moxetumomab pasudotox at any visit are reported.

Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.

Moxetumomab Pasudotox 40 µg/kg

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Intent-to-treat (ITT) population included participants who entered into the study and treated with moxetumomab pasudotox.

Priti Patel

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

Percentage of Participants With Durable Complete Response (CR) Assessed by Blinded Independent Central Review

Percentage of Participants With Durable CR by Investigator's Assessment

MRD negative CR

MRD positive CR

Percentage of Participants With Minimal Residual Disease (MRD) Positive or MRD Negative CR Assessed by Blinded Independent Central Review

Percentage of Participants With MRD Positive or MRD Negative CR by Investigator's Assessment

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Time to CR was evaluated for participants who achieved CR per independent central review.

Time to CR Assessed by Blinded Independent Central Review

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Duration of CR was evaluated for participants who achieved CR per independent central review.

Duration of CR Assessed by Blinded Independent Central Review

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Duration of HR was evaluated for participants who achieved HR.

Duration of Hematologic Remission

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Time to HR was evaluated for participants in the ITT population who achieved HR.

Time to Hematologic Remission

Percentage of Participants With Objective Response (OR) Assessed by Blinded Independent Central Review

Percentage of Participants With Objective Response by Investigator's Assessment

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Time to OR was evaluated for participants who achieved OR per independent central review.

Time to Objective Response Assessed by Blinded Independent Central Review

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Duration of OR was evaluated for participants who achieved OR per independent central review.

Duration of Objective Response Assessed by Blinded Independent Central Review

Progression-free Survival (PFS) Assessed by Blinded Independent Central Review

Time to Treatment Failure (TTF) Assessed by Blinded Independent Central Review

Any TEAEs

Any TESAEs

Safety population included participants who received at least 1 dose of moxetumomab pasudotox.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intraperitoneal tgDCC-E1 and Intravenous Paclitaxel in Women With Platinum-Resistant Ovarian Cancer	NCT00102622	Ovarian Cancer	Intraperitoneal... Paclitaxel	18 Years -	M.D. Anderson Cancer Center
Study of Autologous CAR-T Cells Targeting B7-H3 in TNBC iC9-CAR.B7-H3 T Cells	NCT06347068	Breast Cancer Relapse Resistant Cance... Triple Negative...	iC9-CAR.B7-H3 T... cyclophosphamid... fludarabine	18 Years -	UNC Lineberger Comprehensive Cancer Center
Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia	NCT01829711	Leukemia, Hairy...	Moxetumomab pas... IV Bag Protecta...	18 Years - 100 Years	MedImmune LLC
Moxetumomab Pasudotox-tdfk (Lumoxiti(TM)) and Either Rituximab (Rituxan(R)) or Ruxience for Relapsed Hairy Cell Leukemia	NCT03805932	Hairy Cell Leuk...	Moxetumomab Pas... Rituximab Ruxience Dexamethasone Acetaminophen Diphenhydramine Famotidine Aspirin	18 Years -	National Institutes of Health Clinical Center (CC)
A Study of ZYC300 Administered With Cyclophosphamide Pre-Dosing	NCT00381173	Breast Cancer Ovarian Cancer Prostate Cancer Colon Cancer Renal Cancer	Cyclophosphamid...	18 Years -	Eisai Inc.
Intraperitoneal tgDCC-E1 and Intravenous Paclitaxel in Women With Platinum-Resistant Ovarian Cancer	NCT00102622	Ovarian Cancer	Intraperitoneal... Paclitaxel	18 Years -	M.D. Anderson Cancer Center
Study of Autologous CAR-T Cells Targeting B7-H3 in TNBC iC9-CAR.B7-H3 T Cells	NCT06347068	Breast Cancer Relapse Resistant Cance... Triple Negative...	iC9-CAR.B7-H3 T... cyclophosphamid... fludarabine	18 Years -	UNC Lineberger Comprehensive Cancer Center
Autologous CAR-T Cells Targeting B7H3 in Ovarian Cancer iC9-CAR.B7-H3 T Cells	NCT06305299	Ovary Neoplasm Ovarian Cancer Epithelial Ovar... Recurrent	iC9-CAR.B7-H3 T... Cyclophosphamid... Fludarabine	18 Years -	UNC Lineberger Comprehensive Cancer Center
People-Powered Medicine (PPM): Rheumatoid Arthritis Non-responders to Biologic Therapies (RANT)	NCT05447182	Rheumatoid Arth...		18 Years - 95 Years	Brigham and Women's Hospital
Irinotecan and Bevacizumab for Recurrent Ovarian Cancer	NCT01091259	Ovarian Cancer Fallopian Tube ... Primary Periton...	Irinotecan Bevacizumab	18 Years -	NYU Langone Health
Study of Autologous CAR-T Cells Targeting B7-H3 in TNBC iC9-CAR.B7-H3 T Cells	NCT06347068	Breast Cancer Relapse Resistant Cance... Triple Negative...	iC9-CAR.B7-H3 T... cyclophosphamid... fludarabine	18 Years -	UNC Lineberger Comprehensive Cancer Center

Spots Global Cancer Trial Database for biologic therapy