Cancer, Clinical Oncology, Dermatofibrosarcoma, Ewing's Sarcoma, Ewing's Tumor, Fibrosarcoma, Histiocytoma, Malignant Melanoma, Melanoma, Neoplasia, Neoplasm, Neuroblastoma, Oncology, Medical, Osteogenic Sarcoma, Osteosarcoma Tumor, Pediatrics, Osteosarcoma, Rhabdomyosarcoma, Sarcoma, Ewing's, Sarcoma, Osteogenic, Sarcomas, Epitheliod, Sarcoma, Soft Tissue, Sarcoma, Spindle Cell, Tumors
Conditions
Keywords
Neuroblastoma, Rhabdomyosarcoma, Soft Tissue, Pediatric Oncology, Abraxane, albumin-bound paclitaxel, nab-paclitaxel, ABI-007, taxane, solid tumors
Brief summary
The purpose of this study is to find the safe dose of nab-paclitaxel in children with solid tumors, and to see if it works to treat these solid tumors in children and young adults (in Phase 1 ≤ 18 years old and in Phase 2 ≤ 24 years old). After the final dose has been chosen, patients will be enrolled according to the specific solid tumor type, (neuroblastoma, rhabdomyosarcoma, or Ewing's sarcoma), to see how nab-paclitaxel works in treating these tumors.
Detailed description
ABI-007-PST-001 is a Phase 1/2, multicenter, open-label, dose-finding study to assess the safety , tolerability, and preliminary efficacy of weekly nab-paclitaxel in pediatric patients with recurrent or refractory solid tumors (excluding brain tumors). The Phase 1 portion of the study, with a dose escalation design, ended and the recommended Phase 2 dose (RP2D) was determined as 240 mg/m\^2 intravenously (IV) in patients weighing \> 10 kg and 11.5 mg/kg in patients weighing ≤ 10 kg, on Days 1, 8 and 15 of a 28-day cycle. The Phase 2 portion of the study will enroll additional patients at the RP2D into 1 of 3 solid tumor groups \[neuroblastomas, rhabdomyosarcomas, Ewing's sarcomas\]. Both phases of the study are open-label and conducted at multiple centers. The Phase 2 is using a Simon 2-stage design to monitor patient enrollment for each group separately. The rhabdomyosarcoma group, neuroblastoma or Ewing's sarcoma groups did not reach the expected number of 2 responders out of 14 efficacy eligible patients. Consequently, the groups were stopped.
Interventions
DRUGnab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Sponsors
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 24 Years
Healthy volunteers
No
Inclusion criteria
* Patients must meet all of the following criteria to be enrolled in the study: 1. Patient has a confirmed solid tumor diagnosis according to the following: 1. Phase 1: patient has a recurrent or refractory solid tumor that has progressed or did not respond to standard therapy, or for which no standard anticancer therapy exists 2. Phase 2: patient has radiologically documented measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (for neuroblastoma, evaluable disease by 123\^I-metaiodobenzylguanidine \[MIBG\]/Curie score is also acceptable) in 1 of the following tumor types and has failed up to 3 lines of treatment: Group 1: neuroblastoma, Group 2: rhabdomyosarcoma; Group 3: Ewing's sarcoma. 2. The patient has a Lansky/Karnofsky performance status score of ≥ 70%. 3. The patient has adequate serum chemistry levels, evidenced by the following laboratory values 1. aspartate aminotransferase (AST)/serum glutamic-oxaloacetric transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvate transaminase (SGPT) ≤ 2.5 × upper limit of normal range (ULN) 2. Total bilirubin ≤ 1.5 × ULN 3. Creatinine ≤ 1.5 × ULN 4. The patient has adequate bone marrow function, evidenced by the following: 1. Absolute neutrophil count ≥ 1.0 × 10\^9 cells/L 2. Platelets ≥ 80 × 10\^9 cells/L (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to laboratory sample). In the phase 2 portion, for patients with known bone marrow involvement, platelets ≥ 50 × 10\^9 cells/L 3. Hemoglobin ≥ 8 g/dL (transfusion is permitted to fulfill this criterion). 5. The patient (when applicable) or patient's parent(s) or legal guardian(s) understand(s) and voluntarily signed an informed consent document prior to any study-related assessments/procedures being conducted. Where locally applicable, the patient also understands and voluntarily provides his/her assent prior to any study-related assessments/procedures being conducted. 6. Male patients of childbearing potential must use a condom during sexual intercourse and shall not father a child during the study and for 6 months after the last dose of study medication. 7. Female patients of childbearing potential \[defined as all female patients ≥ 12 years old or who have reached menarche, whichever occurs first\] must have both of the following: a. Agree to the use of two physician-approved contraceptive methods simultaneously or practice complete abstinence while on study medication or for a longer period if required by regulations. i. True abstinence: When this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. ii. Acceptable contraceptive methods include: oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) including at least one barrier method. b. Have negative serum pregnancy test result at screening confirmed by negative urine pregnancy dipstick within 72 hours prior to first dose of investigational product (if serum test occurred \> 72 hours from first dose); pregnancy test with sensitivity of at least 25 mIU/mL.
Exclusion criteria
* The presence of any of the following will exclude a patient from enrollment: <!-- --> 1. The patient has a primary brain tumor(s) or brain metastasis (unless metastasis is treated and stable for \> 28 days). In patients who are symptomatic, a brain scan is required to exclude metastasis. 2. The patient has received therapeutic dose chemotherapy or radiotherapy ≤ 21 days prior to start of investigational product. 3. The patient has received maintenance dose chemotherapy (e.g., low dose cyclophosphamide) ≤ 7 days from the first dose of investigational product. 4. The patient has received any investigational therapy ≤ 28 days prior to start of investigational product. Investigational therapy is defined as any medicinal product that is not approved in the country of treatment for any indication, adult or pediatric. 5. The patient has received any biological therapy ≤ 7 days prior to the start of investigational product, or monoclonal antibody ≤ 3 half-lives or 28 days, whichever is shorter, prior to the first dose of investigational product. 6. The patient has received any hematopoietic stem cell transplantation (HSCT) ≤ 3 months prior to start of investigational product. 7. The patient has received allogeneic hematopoietic stem cell transplantation (HSCT) ≤ 3 months or autologous HSCT ≤ 21 days prior to start of investigational product. 8. The patient has not recovered from the acute toxic effects of prior chemotherapy, radiation, or major surgery/significant trauma. 9. The patient has had minor surgery ≤ 7 days from the start of study treatment (excluding the placement of central/peripheral lines, skin biopsy). 10. The patient has a known history of stroke, myocardial infarction, peripheral vascular disease, or recent (within 3 months) uncontrolled deep venous thrombosis. 11. The patient has a known history or current diagnosis of human immunodeficiency virus (HIV) infection, regardless of treatment status. 12. The patient has an uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 13. The patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study. 14. The patient has any condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk if he/she were to participate in the study. 15. The patient has any condition that confounds the ability to interpret data from the study. 16. The patient or parent(s)/guardian(s) is/are unable to comply with the study visit schedule and other protocol requirements, in the opinion of the investigator. 17. The patient has ≥ Grade 2 peripheral neuropathy by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | DLT assessment period: For participants > 10 kg: the first 28-day cycle including Cycle 2 Day 1 predose evaluations; for participants ≤ 10 kg: the first two 28-day cycles including Cycle 3 Day 1 predose evaluations | A DLT was defined as investigational product (IP)-related adverse events occurring during the DLT assessment period that led to treatment discontinuation or met one of the following criteria: - Common Terminology Criteria for Adverse Events (CTCAE) Grade (Gr) 3 or 4 nonhematologic toxicity (excluding transient transaminitis) - CTCAE Gr 3 or 4 nausea or vomiting that persisted \> 5 days despite maximal anti-emetic treatment - CTCAE Gr 4 thrombocytopenia or anemia that persisted \> 7 days or required transfusion \> 7 days - CTCAE Gr 3 thrombocytopenia with bleeding - CTCAE Gr 4 uncomplicated neutropenia lasting \> 7 days - Febrile neutropenia with confirmed bacterial infection - CTCAE Gr 3 hematologic toxicity requiring treatment (tx) delay \> 21 days. Use of ... in the table rows signifies the continuation of row title per the above list. |
| Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs. | An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE (SAE) is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of an AE was graded according to the CTCAE, Version 4.0. |
| Phase 2: Overall Response Rate (ORR) | Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). | Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. (For Phase 2 neuroblastoma participants who had both RECIST and Curie Score tumor evaluations, both tumor response results were considered and an overall response was derived.) Confidence interval was obtained using the Clopper-Pearson method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Measurements include: AUC from time zero to the last measurable concentration (AUCt), AUC from time zero to 24 hours (AUC24), and AUC from time zero to infinity (AUCinf). |
| Phase 1: AUC - Dose-Normalized | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Measurements include: AUC24 and AUCinf. |
| Phase 1: Clearance (CL) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Measurement of renal clearance from the body. |
| Phase 1: CL - Body Surface Area (BSA)-Normalized | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Measurement of renal clearance from the body. |
| Phase 1: Volume of Distribution (Vss) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | — |
| Phase 1: Vss - BSA-Normalized | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | — |
| Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V1 was 0.888. |
| Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for VMEL was 1.12. |
| Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Population PK analysis was performed using nonlinear mixed effect modeling. |
| Phase 1: ORR | Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. | Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met) using RECIST version 1.1 guidelines over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method. |
| Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q3 was 1.12. |
| Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V2 was 0.888. |
| Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V3 was 0.888. |
| Phase 2: Duration of Response (DOR) | Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks. | Duration of response was defined as the time from the date of the first response (CR/PR, using RECIST version 1.1 guidelines) to disease progression for participants with a confirmed CR or PR. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at time of start of new anticancer therapy, whichever occurred first. (For Phase 2 neuroblastoma patients who had both RECIST version 1.1 and Curie Score tumor evaluations, both tumor responses results were considered and an overall response was derived.) |
| Phase 2: Disease Control Rate (DCR) | Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). | Disease control rate was defined as the percentage of participants who achieved either a stable disease maintained for ≥ 16 weeks or confirmed CR (confirmed no less than 4 weeks after criteria for response were first met) or confirmed PR (confirmed no less than 4 weeks after criteria for response were first met) over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method. |
| Phase 2: Progression-Free Survival (PFS) | Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks. | PFS was defined as the time from the first dose date to the start of disease progression or participant death (any cause), whichever occurred first. Disease progression was classed as either a disease progression observed as a response assessment, or a disease progression or symptomatic deterioration at treatment/study discontinuation. Participants who did not have disease progression or had not died were censored at the last known time that the participant was progression free. Disease progression was considered according to RECIST version 1.1 for Phase 2 Ewing's sarcoma and rhabdomyosarcoma participants. (For Phase 2 neuroblastoma participants who had both RECIST 1.1 and Curie score tumor evaluations, both tumor responses results were considered and an overall response was derived.) Median PFS time was estimated through Kaplan-Meier methods. 95% confidence interval about the median time to PFS event was obtained using Greenwood's method. |
| Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year | 1 year | Overall survival was defined as the time from the first dose date to date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive. |
| Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs. | An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A SAE is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of the AEs was graded according to the Common Terminology Criteria for Adverse Events, Version 4.0. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs. |
| Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q2 was 1.12. |
| Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | — |
| Phase 1: Cmax - Dose-Normalized | Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.) | — |
Countries
Canada, France, Italy, Spain, Switzerland, United Kingdom, United States
Participant flow
Pre-assignment details
Sixty-five participants were included in the Phase 1 enrolled population, and 64 enrolled partcipants received at least 1 dose of study drug and were included in the safety population, noted below. Forty-two participants were included in the Phase 2 enrolled and safety populations.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 nab-paclitaxel 120 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. | 16 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 nab-paclitaxel 150 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. | 8 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 nab-paclitaxel 180 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. | 14 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 nab-paclitaxel 210 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. | 11 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 nab-paclitaxel 240 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. | 8 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 nab-paclitaxel 270 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. | 7 |
| Phase 2: Ewing's Sarcoma Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m\^2 in participants weighing \> 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. | 14 |
| Phase 2: Neuroblastoma Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m\^2 in participants weighing \> 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. | 14 |
| Phase 2: Rhabdomyosarcoma Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m\^2 in participants weighing \> 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. | 14 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Phase 1 | Adverse Event | 4 | 0 | 2 | 1 | 2 | 2 | 0 | 0 | 0 |
| Phase 1 | Miscellaneous | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 | Progressive Disease | 8 | 6 | 8 | 4 | 5 | 4 | 0 | 0 | 0 |
| Phase 1 | Symptomatic Deterioration | 3 | 2 | 2 | 2 | 1 | 1 | 0 | 0 | 0 |
| Phase 1 | Withdrawal by Parent/Guardian | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Phase 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 |
| Phase 2 | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 12 | 11 |
| Phase 2 | Symptomatic Deterioration | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Phase 2: Rhabdomyosarcoma | Phase 2: Neuroblastoma | Phase 2: Ewing's Sarcoma | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 10.7 years STANDARD_DEVIATION 4.81 | 12.4 years STANDARD_DEVIATION 6.42 | 7.1 years STANDARD_DEVIATION 3.42 | 10.1 years STANDARD_DEVIATION 4.63 | 12.1 years STANDARD_DEVIATION 2.97 | 11.6 years STANDARD_DEVIATION 4.63 | 10.2 years STANDARD_DEVIATION 5.36 | 12.1 years STANDARD_DEVIATION 5.84 | 11.7 years STANDARD_DEVIATION 3.32 | 10.2 years STANDARD_DEVIATION 4.64 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 8 Participants | 8 Participants | 11 Participants | 5 Participants | 5 Participants | 10 Participants | 5 Participants | 6 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 24 Participants | 1 Participants | 4 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 6 Participants |
| Number of Prior Systemic Anticancer Regimens Received | 2.99 systemic anticancer regimens STANDARD_DEVIATION 1.552 | 2.21 systemic anticancer regimens STANDARD_DEVIATION 0.579 | 2.14 systemic anticancer regimens STANDARD_DEVIATION 0.663 | 2.50 systemic anticancer regimens STANDARD_DEVIATION 0.519 | 3.00 systemic anticancer regimens STANDARD_DEVIATION 0.816 | 3.00 systemic anticancer regimens STANDARD_DEVIATION 1.309 | 3.64 systemic anticancer regimens STANDARD_DEVIATION 2.461 | 3.25 systemic anticancer regimens STANDARD_DEVIATION 1.832 | 3.69 systemic anticancer regimens STANDARD_DEVIATION 1.815 | 3.64 systemic anticancer regimens STANDARD_DEVIATION 1.946 |
| Participants With Any Prior Cancer Treatment Any Prior Cancer Treatment | 106 Participants | 14 Participants | 14 Participants | 14 Participants | 7 Participants | 8 Participants | 11 Participants | 8 Participants | 16 Participants | 14 Participants |
| Participants With Any Prior Cancer Treatment Other Prior Anticancer Therapies | 15 Participants | 0 Participants | 6 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Participants With Any Prior Cancer Treatment Prior Cancer Surgeries | 78 Participants | 6 Participants | 11 Participants | 10 Participants | 7 Participants | 5 Participants | 9 Participants | 7 Participants | 14 Participants | 9 Participants |
| Participants With Any Prior Cancer Treatment Prior Radiation Therapy | 75 Participants | 10 Participants | 10 Participants | 12 Participants | 6 Participants | 6 Participants | 7 Participants | 4 Participants | 9 Participants | 11 Participants |
| Participants With Any Prior Cancer Treatment Prior Stem Cell Transplants | 27 Participants | 0 Participants | 10 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants |
| Participants With Any Prior Cancer Treatment Prior Systemic Anticancer Regimens | 106 Participants | 14 Participants | 14 Participants | 14 Participants | 7 Participants | 8 Participants | 11 Participants | 8 Participants | 16 Participants | 14 Participants |
| Participants With Any Prior Cancer Treatment Prior Systemic Anticancer Therapy | 106 Participants | 14 Participants | 14 Participants | 14 Participants | 7 Participants | 8 Participants | 11 Participants | 8 Participants | 16 Participants | 14 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Collected or Reported | 18 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 84 Participants | 12 Participants | 11 Participants | 11 Participants | 5 Participants | 8 Participants | 9 Participants | 8 Participants | 11 Participants | 9 Participants |
| Sex: Female, Male Female | 53 Participants | 9 Participants | 5 Participants | 6 Participants | 3 Participants | 1 Participants | 7 Participants | 4 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Male | 53 Participants | 5 Participants | 9 Participants | 8 Participants | 4 Participants | 7 Participants | 4 Participants | 4 Participants | 7 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 14 / 16 | 7 / 8 | 11 / 14 | 5 / 11 | 8 / 8 | 5 / 7 | 25 / 42 |
| other Total, other adverse events | 16 / 16 | 8 / 8 | 14 / 14 | 11 / 11 | 8 / 8 | 7 / 7 | 42 / 42 |
| serious Total, serious adverse events | 10 / 16 | 7 / 8 | 6 / 14 | 5 / 11 | 3 / 8 | 4 / 7 | 23 / 42 |
Outcome results
Primary
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as investigational product (IP)-related adverse events occurring during the DLT assessment period that led to treatment discontinuation or met one of the following criteria: - Common Terminology Criteria for Adverse Events (CTCAE) Grade (Gr) 3 or 4 nonhematologic toxicity (excluding transient transaminitis) - CTCAE Gr 3 or 4 nausea or vomiting that persisted \> 5 days despite maximal anti-emetic treatment - CTCAE Gr 4 thrombocytopenia or anemia that persisted \> 7 days or required transfusion \> 7 days - CTCAE Gr 3 thrombocytopenia with bleeding - CTCAE Gr 4 uncomplicated neutropenia lasting \> 7 days - Febrile neutropenia with confirmed bacterial infection - CTCAE Gr 3 hematologic toxicity requiring treatment (tx) delay \> 21 days. Use of ... in the table rows signifies the continuation of row title per the above list.
Time frame: DLT assessment period: For participants > 10 kg: the first 28-day cycle including Cycle 2 Day 1 predose evaluations; for participants ≤ 10 kg: the first two 28-day cycles including Cycle 3 Day 1 predose evaluations
Population: Dose Determining Set (DDS): all Phase 1 participants who received all 3 weekly doses of nab-paclitaxel at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT assessment period or experienced a DLT. The DDS did not include participants who were enrolled at each dose once the dose had been determined to be safe.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nausea or Vomiting Persisting >5 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nonhematologic Toxicity... | 1 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | At least 1 DLT | 1 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Thrombocytopenia/Anemia Persisting >7 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3 Thrombocytopenia with Bleeding | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Uncomplicated Neutropenia Lasting >7 days | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Febrile Neutropenia+Confirmed Bacterial Infection | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr3 Hematologic Toxicity Requiring Tx Delay... | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Thrombocytopenia/Anemia Persisting >7 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr3 Hematologic Toxicity Requiring Tx Delay... | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | At least 1 DLT | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Febrile Neutropenia+Confirmed Bacterial Infection | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Uncomplicated Neutropenia Lasting >7 days | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nausea or Vomiting Persisting >5 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nonhematologic Toxicity... | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3 Thrombocytopenia with Bleeding | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nonhematologic Toxicity... | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nausea or Vomiting Persisting >5 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Thrombocytopenia/Anemia Persisting >7 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr3 Hematologic Toxicity Requiring Tx Delay... | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3 Thrombocytopenia with Bleeding | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Uncomplicated Neutropenia Lasting >7 days | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Febrile Neutropenia+Confirmed Bacterial Infection | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | At least 1 DLT | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Febrile Neutropenia+Confirmed Bacterial Infection | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Uncomplicated Neutropenia Lasting >7 days | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3 Thrombocytopenia with Bleeding | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | At least 1 DLT | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nausea or Vomiting Persisting >5 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Thrombocytopenia/Anemia Persisting >7 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr3 Hematologic Toxicity Requiring Tx Delay... | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nonhematologic Toxicity... | 0 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr3 Hematologic Toxicity Requiring Tx Delay... | 0 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | At least 1 DLT | 0 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3 Thrombocytopenia with Bleeding | 0 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Uncomplicated Neutropenia Lasting >7 days | 0 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Febrile Neutropenia+Confirmed Bacterial Infection | 0 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nonhematologic Toxicity... | 0 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nausea or Vomiting Persisting >5 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Thrombocytopenia/Anemia Persisting >7 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr3 Hematologic Toxicity Requiring Tx Delay... | 0 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3 Thrombocytopenia with Bleeding | 0 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nausea or Vomiting Persisting >5 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Thrombocytopenia/Anemia Persisting >7 days... | 0 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 4 Uncomplicated Neutropenia Lasting >7 days | 1 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Gr 3/4 Nonhematologic Toxicity... | 0 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Febrile Neutropenia+Confirmed Bacterial Infection | 0 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | At least 1 DLT | 1 Participants |
Primary
Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE (SAE) is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of an AE was graded according to the CTCAE, Version 4.0.
Time frame: Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
Population: Safety Population: all participants who took at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 10 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 TEAE | 13 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 16 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Grade 3 or 4 TEAE | 9 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 2 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Interruption | 2 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Dose Reduction | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Dose Reduction | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related (TR) TEAE | 14 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Interruption | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Discontinuation | 1 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Discontinuation | 4 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Serious TEAE | 1 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related (TR) TEAE | 8 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Interruption | 2 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 8 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 TEAE | 8 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Grade 3 or 4 TEAE | 7 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 7 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Serious TEAE | 4 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Discontinuation | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Discontinuation | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Dose Reduction | 1 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Dose Reduction | 1 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Interruption | 2 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 1 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Dose Reduction | 2 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Serious TEAE | 4 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 TEAE | 10 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related (TR) TEAE | 12 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Interruption | 1 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Discontinuation | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Grade 3 or 4 TEAE | 7 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Interruption | 3 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 14 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Dose Reduction | 2 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Discontinuation | 2 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 6 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Discontinuation | 1 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Dose Reduction | 1 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Serious TEAE | 2 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 11 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Grade 3 or 4 TEAE | 9 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related (TR) TEAE | 11 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Interruption | 4 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 5 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Discontinuation | 1 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 TEAE | 10 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Interruption | 3 Participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Dose Reduction | 1 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Discontinuation | 2 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 3 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related (TR) TEAE | 7 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 1 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Serious TEAE | 1 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Discontinuation | 2 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Dose Reduction | 3 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 8 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Dose Reduction | 3 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Interruption | 3 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Interruption | 3 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 TEAE | 8 Participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Grade 3 or 4 TEAE | 7 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 4 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Interruption | 2 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 7 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related (TR) TEAE | 7 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Discontinuation | 2 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Grade 3 or 4 TEAE | 7 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 TEAE | 7 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Discontinuation | 2 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 1 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Dose Reduction | 3 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Dose Reduction | 3 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Serious TEAE | 3 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Interruption | 2 Participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Death | 0 Participants |
Primary
Phase 2: Overall Response Rate (ORR)
Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. (For Phase 2 neuroblastoma participants who had both RECIST and Curie Score tumor evaluations, both tumor response results were considered and an overall response was derived.) Confidence interval was obtained using the Clopper-Pearson method.
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).
Population: Efficacy Evaluable Population: participants who met eligibility criteria for Phase 2, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Overall Response Rate (ORR) | 0 percentage of participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Overall Response Rate (ORR) | 0 percentage of participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Overall Response Rate (ORR) | 7.1 percentage of participants |
Secondary
Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL)
Population PK analysis was performed using nonlinear mixed effect modeling.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL) | 951 μg/L |
Secondary
Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q2 was 1.12.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2) | 22.4 L/h |
Secondary
Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q3 was 1.12.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3) | 34.8 L/h |
Secondary
Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for VMEL was 1.12.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL) | 31983 μg/h |
Secondary
Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V1 was 0.888.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1) | 11.8 liters |
Secondary
Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V2 was 0.888.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2) | 545 liters |
Secondary
Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V3 was 0.888.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3) | 45.3 liters |
Secondary
Phase 1: Area Under the Plasma Concentration-Time Curve (AUC)
Measurements include: AUC from time zero to the last measurable concentration (AUCt), AUC from time zero to 24 hours (AUC24), and AUC from time zero to infinity (AUCinf).
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data for given measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUC24 | 6392 ng*h/mL | Geometric Coefficient of Variation 79 |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCt | 7844 ng*h/mL | Geometric Coefficient of Variation 73.4 |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCinf | 8867 ng*h/mL | Geometric Coefficient of Variation 85.4 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUC24 | 8944 ng*h/mL | Geometric Coefficient of Variation 85.9 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCt | 10374 ng*h/mL | Geometric Coefficient of Variation 91.8 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCinf | 11992 ng*h/mL | Geometric Coefficient of Variation 99.8 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUC24 | 8365 ng*h/mL | Geometric Coefficient of Variation 37.7 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCt | 9690 ng*h/mL | Geometric Coefficient of Variation 37.1 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCinf | 10087 ng*h/mL | Geometric Coefficient of Variation 38.4 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUC24 | 10932 ng*h/mL | Geometric Coefficient of Variation 66.3 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCt | 11817 ng*h/mL | Geometric Coefficient of Variation 64 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCinf | 14361 ng*h/mL | Geometric Coefficient of Variation 72.1 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUC24 | 11167 ng*h/mL | Geometric Coefficient of Variation 27.4 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCt | 12706 ng*h/mL | Geometric Coefficient of Variation 29.2 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCinf | 14242 ng*h/mL | Geometric Coefficient of Variation 29.2 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCt | 11245 ng*h/mL | Geometric Coefficient of Variation 22.6 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUCinf | 12424 ng*h/mL | Geometric Coefficient of Variation 28.5 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) | AUC24 | 9768 ng*h/mL | Geometric Coefficient of Variation 20.7 |
Secondary
Phase 1: AUC - Dose-Normalized
Measurements include: AUC24 and AUCinf.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data for given measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUC24 | 42.7 ng*h/mL/[mg] | Geometric Coefficient of Variation 77.4 |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUCinf | 62.0 ng*h/mL/[mg] | Geometric Coefficient of Variation 75.7 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUC24 | 41.6 ng*h/mL/[mg] | Geometric Coefficient of Variation 87 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUCinf | 49.2 ng*h/mL/[mg] | Geometric Coefficient of Variation 101 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUC24 | 40.8 ng*h/mL/[mg] | Geometric Coefficient of Variation 39.7 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUCinf | 47.8 ng*h/mL/[mg] | Geometric Coefficient of Variation 39.8 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUC24 | 43.3 ng*h/mL/[mg] | Geometric Coefficient of Variation 63.6 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUCinf | 64.8 ng*h/mL/[mg] | Geometric Coefficient of Variation 25.4 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUC24 | 40.2 ng*h/mL/[mg] | Geometric Coefficient of Variation 65.4 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUCinf | 52.3 ng*h/mL/[mg] | Geometric Coefficient of Variation 67.4 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUC24 | 25.4 ng*h/mL/[mg] | Geometric Coefficient of Variation 26.1 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: AUC - Dose-Normalized | AUCinf | 31.3 ng*h/mL/[mg] | Geometric Coefficient of Variation 34.9 |
Secondary
Phase 1: CL - Body Surface Area (BSA)-Normalized
Measurement of renal clearance from the body.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: CL - Body Surface Area (BSA)-Normalized | 13.5 L/h/m^2 | Geometric Coefficient of Variation 85.1 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: CL - Body Surface Area (BSA)-Normalized | 12.5 L/h/m^2 | Geometric Coefficient of Variation 99.3 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: CL - Body Surface Area (BSA)-Normalized | 17.8 L/h/m^2 | Geometric Coefficient of Variation 38.3 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: CL - Body Surface Area (BSA)-Normalized | 14.6 L/h/m^2 | Geometric Coefficient of Variation 72.3 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: CL - Body Surface Area (BSA)-Normalized | 16.7 L/h/m^2 | Geometric Coefficient of Variation 29.2 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: CL - Body Surface Area (BSA)-Normalized | 21.8 L/h/m^2 | Geometric Coefficient of Variation 28.4 |
Secondary
Phase 1: Clearance (CL)
Measurement of renal clearance from the body.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Clearance (CL) | 16.1 L/h | Geometric Coefficient of Variation 75.6 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Clearance (CL) | 20.3 L/h | Geometric Coefficient of Variation 101 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Clearance (CL) | 20.9 L/h | Geometric Coefficient of Variation 39.9 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Clearance (CL) | 15.4 L/h | Geometric Coefficient of Variation 25.4 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Clearance (CL) | 19.1 L/h | Geometric Coefficient of Variation 67.4 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Clearance (CL) | 31.9 L/h | Geometric Coefficient of Variation 35 |
Secondary
Phase 1: Cmax - Dose-Normalized
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Cmax - Dose-Normalized | 23.3 ng/mL/[mg] | Geometric Coefficient of Variation 87.5 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Cmax - Dose-Normalized | 25.4 ng/mL/[mg] | Geometric Coefficient of Variation 46.6 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Cmax - Dose-Normalized | 27.3 ng/mL/[mg] | Geometric Coefficient of Variation 47.3 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Cmax - Dose-Normalized | 23.2 ng/mL/[mg] | Geometric Coefficient of Variation 80.3 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Cmax - Dose-Normalized | 28.2 ng/mL/[mg] | Geometric Coefficient of Variation 48.7 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Cmax - Dose-Normalized | 21.0 ng/mL/[mg] | Geometric Coefficient of Variation 46.6 |
Secondary
Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax)
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: Pharmacokinetic (PK) population: all participannts who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) | 3488 ng/mL | Geometric Coefficient of Variation 73.7 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) | 5468 ng/mL | Geometric Coefficient of Variation 38 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) | 5597 ng/mL | Geometric Coefficient of Variation 33.4 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) | 5616 ng/mL | Geometric Coefficient of Variation 63.9 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) | 7831 ng/mL | Geometric Coefficient of Variation 23.1 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) | 8078 ng/mL | Geometric Coefficient of Variation 41.5 |
Secondary
Phase 1: ORR
Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met) using RECIST version 1.1 guidelines over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
Time frame: Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively.
Population: Efficacy Evaluable Population: participants who met eligibility criteria for Phase 1, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: ORR | 0 percentage of participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: ORR | 0 percentage of participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: ORR | 0 percentage of participants |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: ORR | 0 percentage of participants |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: ORR | 12.5 percentage of participants |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: ORR | 14.3 percentage of participants |
Secondary
Phase 1: Volume of Distribution (Vss)
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Volume of Distribution (Vss) | 127 liters | Geometric Coefficient of Variation 145 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Volume of Distribution (Vss) | 266 liters | Geometric Coefficient of Variation 78.3 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Volume of Distribution (Vss) | 146 liters | Geometric Coefficient of Variation 106 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Volume of Distribution (Vss) | 89.8 liters | Geometric Coefficient of Variation 45.1 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Volume of Distribution (Vss) | 175 liters | Geometric Coefficient of Variation 117 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Volume of Distribution (Vss) | 446 liters | Geometric Coefficient of Variation 17.6 |
Secondary
Phase 1: Vss - BSA-Normalized
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Population: PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Vss - BSA-Normalized | 106 L/m^2 | Geometric Coefficient of Variation 95.3 |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Vss - BSA-Normalized | 164 L/m^2 | Geometric Coefficient of Variation 78.4 |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Vss - BSA-Normalized | 124 L/m^2 | Geometric Coefficient of Variation 82.8 |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Vss - BSA-Normalized | 84.9 L/m^2 | Geometric Coefficient of Variation 49.7 |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Vss - BSA-Normalized | 154 L/m^2 | Geometric Coefficient of Variation 56.5 |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 1: Vss - BSA-Normalized | 304 L/m^2 | Geometric Coefficient of Variation 29 |
Secondary
Phase 2: Disease Control Rate (DCR)
Disease control rate was defined as the percentage of participants who achieved either a stable disease maintained for ≥ 16 weeks or confirmed CR (confirmed no less than 4 weeks after criteria for response were first met) or confirmed PR (confirmed no less than 4 weeks after criteria for response were first met) over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).
Population: Efficacy Evaluable Population: participants who met eligibility criteria for Phase 2, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Disease Control Rate (DCR) | 30.8 percentage of participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Disease Control Rate (DCR) | 7.1 percentage of participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Disease Control Rate (DCR) | 7.1 percentage of participants |
Secondary
Phase 2: Duration of Response (DOR)
Duration of response was defined as the time from the date of the first response (CR/PR, using RECIST version 1.1 guidelines) to disease progression for participants with a confirmed CR or PR. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at time of start of new anticancer therapy, whichever occurred first. (For Phase 2 neuroblastoma patients who had both RECIST version 1.1 and Curie Score tumor evaluations, both tumor responses results were considered and an overall response was derived.)
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.
Population: Efficacy Evaluable Population: participants (with response) who met eligibility criteria for Phase 2, completed ≥ 1 dose of study drug, and had baseline and ≥ 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Duration of Response (DOR) | 6.14 weeks |
Secondary
Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year
Overall survival was defined as the time from the first dose date to date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.
Time frame: 1 year
Population: Efficacy Evaluable Population: participants who met eligibility criteria for Phase 2, completed ≥1 dose of study drug, and had baseline and ≥1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year | 48 percentage of participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year | 25 percentage of participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year | 15 percentage of participants |
Secondary
Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A SAE is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of the AEs was graded according to the Common Terminology Criteria for Adverse Events, Version 4.0. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
Population: Safety Population: all participants who took at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Interruption | 5 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Serious TEAE | 2 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 TEAE | 12 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Dose Reduction | 4 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Discontinuation | 3 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related (TR) TEAE | 13 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Dose Reduction | 4 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Discontinuation | 1 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Interruption | 3 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Grade 3 or 4 TEAE | 9 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 14 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 6 Participants |
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Interruption | 3 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 14 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related (TR) TEAE | 12 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 TEAE | 13 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Grade 3 or 4 TEAE | 9 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 6 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Serious TEAE | 2 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Discontinuation | 1 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Discontinuation | 0 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Dose Reduction | 5 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Dose Reduction | 4 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Interruption | 3 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 2 Participants |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 3 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Dose Reduction | 4 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 11 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Grade 3 or 4 TEAE | 10 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Interruption | 4 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 TEAE | 12 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 14 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Interruption | 2 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related (TR) TEAE | 12 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Drug Discontinuation | 3 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Drug Discontinuation | 3 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR TEAE Leading to Death | 0 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Dose Reduction | 4 Participants |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TR Serious TEAE | 6 Participants |
Secondary
Phase 2: Progression-Free Survival (PFS)
PFS was defined as the time from the first dose date to the start of disease progression or participant death (any cause), whichever occurred first. Disease progression was classed as either a disease progression observed as a response assessment, or a disease progression or symptomatic deterioration at treatment/study discontinuation. Participants who did not have disease progression or had not died were censored at the last known time that the participant was progression free. Disease progression was considered according to RECIST version 1.1 for Phase 2 Ewing's sarcoma and rhabdomyosarcoma participants. (For Phase 2 neuroblastoma participants who had both RECIST 1.1 and Curie score tumor evaluations, both tumor responses results were considered and an overall response was derived.) Median PFS time was estimated through Kaplan-Meier methods. 95% confidence interval about the median time to PFS event was obtained using Greenwood's method.
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.
Population: Efficacy Evaluable Population: participants who met eligibility criteria for Phase 2, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 2: Progression-Free Survival (PFS) | 13 weeks |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 2: Progression-Free Survival (PFS) | 7.4 weeks |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 2: Progression-Free Survival (PFS) | 5.1 weeks |