Metastatic Melanoma
Conditions
Keywords
Melanoma, Adoptive Cell Therapy
Brief summary
Background: * The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 400 patients with melanoma. * In this trial, we are determining if there is a difference in the response between patients who have received prior anti-programmed cell death-1 (PD-1) treatment to those who have not received this prior ant-PD1 treatment. Objectives: \- To determine if there is a difference in the rate of response between patients who have received prior anti-PD1 and those who have not. Eligibility: \- Individuals at least 18 years and less than or equal to 70 years of age who have metastatic melanoma. Design: * Work up stage: Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. * Surgery: Surgery or biopsy will be performed to obtain tumor from which to grow white blood cells. White blood cells will be grown from the tumor in the laboratory. * Leukapheresis: Participants will have leukapheresis to collect additional white blood cells. (Leukapheresis is a common procedure which removes only the white blood cells from the patient.) * Treatment: Participants will receive standard dose chemotherapy to prepare their immune system to accept the white blood cells. Participants will receive an infusion of their own white blood cells grown from tumor. They will also receive aldesleukin for up to five days to boost the immune system s response to the white blood cells. They will stay in the hospital for about 4 weeks for the treatment. * Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.
Detailed description
Background: * Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes can mediate the regression of bulky metastatic melanoma when administered along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine. * In a series of consecutive trials using this chemotherapy preparative regimen alone or with 2 Gray (Gy) or 12 Gy total body irradiation (TBI) objective response rates using Response Evaluation Criteria In Solid Tumors (RECIST) criteria were 49%, 52%, and 72%, respectively. Of the 20 complete regressions seen in this trial, 19 are on-going at 70 to 114 months. * The chemotherapy alone preparative regimen required in-patient treatment and was associated with significant neutropenia and thrombocytopenia requiring multiple transfusions and treatment for febrile neutropenia. Objectives: * With amendment D, to determine if there is a difference in the rate of response between patients who have received prior anti-PD1 and those who have not; both groups will receive non-myeloablative lymphoid depleting preparative regimen followed by autologous young tumor infiltrating lymphocytes (TIL) and administration of high dose aldesleukin. * To determine the toxicity of the treatment. Eligibility: * Age greater than or equal to 18 and less than or equal to 70 years * Evaluable metastatic melanoma * Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL * No contraindications to high-dose aldesleukin administration * No concurrent major medical illnesses or any form of immunodeficiency Design: * Patients with metastatic melanoma will have lesions resected and after TIL growth is established, patients will receive ACT with TIL plus aldesleukin following high dose chemotherapy preparative regimen. * Up to 64 patients may be enrolled over 4-5 years.
Interventions
DRUGAldesleukin
720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
DRUGFludarabine
25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days
DRUGCyclophosphamide
60 mg/kg/day X 2 days intravenous (IV)
BIOLOGICALYoung TIL
Day 0: Cells will be infused intravenously (IV)
DRUGPembrolizumab
2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
-INCLUSION CRITERIA: 1. Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation and at least one other lesion that can be measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. 2. Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of National Cancer Institute (NCI). 3. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible. 4. Greater than or equal to 18 years of age and less than or equal to 70 years of age. 5. Ability of subject to understand and the willingness to sign the Informed Consent Document 6. Willing to sign a durable power of attorney. 7. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2. 8. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment. 9. Serology: * Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.) * Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative. 10. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. 11. Hematology: * Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim * White blood cell (WBC) greater than or equal to 3000/mm(3) * Platelet count greater than or equal to 100,000/mm(3) * Hemoglobin \> 8.0 g/dl 12. Chemistry: * Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to 2.5 times the upper limit of normal * Serum Creatinine less than or equal to 1.6 mg/dl * Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl. 13. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients must have progressive disease after prior treatment. Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less. 14. Subjects must be co-enrolled in 03-C-0277
Exclusion criteria
1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. 2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). 3. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities). 4. Active systemic infections, (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses. 5. Concurrent systemic steroid therapy. 6. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 7. History of coronary revascularization or ischemic symptoms. 8. Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45% 9. Documented LVEF of less than or equal to 45%, note: testing is required in patients with: * Age greater than or equal to 65 years old * Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or history of ischemic heart disease or chest pain. 10. Patients who are receiving other investigational agents 11. Documented forced expiratory volume (FEV1) less than or equal to 60% predicted tested in patients with: * A prolonged history of cigarette smoking (20 pack (pk)/year of smoking within the past 2 years). * Symptoms of respiratory dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Date of cells until time of disease progression, up to approximately 67.2 months. | Overall response is the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.0). Progression is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | 30 days after end of treatment | Number of participants with Grades 3-5 treatment-related adverse events were compared in Arm 1N and Arm 1P; and adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening, and Grade 5 is death related to adverse event. |
| Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | 4 weeks after cell infusion, then every 3 months x 3 and then every 6 months for 5 years, then per Principal Investigator (PI) discretion up to 5 years or disease progression | Clinical response to treatment was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST v1.0). Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Date of cells until time to death, up until 90.1 months. | Overall survival is defined as the time from treatment start date until date of death, or date last known alive. |
| Overall Progression Free Survival (PFS) | Time to progression and time to death, approximately up to 67.2 months. | PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Number of Treatment-related Adverse Events for Participants Who Received Pembrolizumab | Date treatment consent signed until approximately 4 weeks following last dose of Pembrolizumab, up to 4 weeks | Number of treatment-related adverse events for participants who received pembrolizumab. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. |
| Progression-free Survival (PFS) | Date of cells until time of disease progression up to approximately 67.2 months. | PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively. | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) | 8 |
| Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) | 11 |
| Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV. | 3 |
| Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days.
Young TIL: Day 0: Cells will be infused intravenously (IV) | 9 |
| Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). | 2 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| First Drug Administration | Not treated | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 10 Participants | 3 Participants | 9 Participants | 2 Participants | 32 Participants |
| Age, Continuous | 46.28 years STANDARD_DEVIATION 1.43 | 56.28 years STANDARD_DEVIATION 13.39 | 31.07 years STANDARD_DEVIATION 13.25 | 44.72 years STANDARD_DEVIATION 3.66 | 53 years STANDARD_DEVIATION 3.39 | 46.45 years STANDARD_DEVIATION 13.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 11 Participants | 3 Participants | 9 Participants | 2 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 11 Participants | 3 Participants | 9 Participants | 2 Participants | 33 Participants |
| Region of Enrollment United States | 8 participants | 11 participants | 3 participants | 9 participants | 2 participants | 33 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 1 Participants | 5 Participants | 1 Participants | 22 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 7 | 9 / 11 | 2 / 3 | 8 / 9 | 1 / 2 |
| other Total, other adverse events | 7 / 7 | 9 / 11 | 3 / 3 | 9 / 9 | 2 / 2 |
| serious Total, serious adverse events | 3 / 7 | 6 / 11 | 1 / 3 | 2 / 9 | 1 / 2 |
Outcome results
Primary
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
Clinical response to treatment was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST v1.0). Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
Time frame: 4 weeks after cell infusion, then every 3 months x 3 and then every 6 months for 5 years, then per Principal Investigator (PI) discretion up to 5 years or disease progression
Population: The first combined group (n=16) is Arm 1P, the second treatment of Arm 2/1P, the initial treatment of Arm 1P/R. The second group (n=7) is Arm 1N (1/8 participants was not treated). The third group (n=12) is Arm 2 and the initial treatment of Arm 2/1P. The final group (n=2) will report the second treatment of Arm 1P/R. This enables reporting of the 37 treatments among the 32 treated participants separated by exposure to pembrolizumab/nivolumab and chemo dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Complete Response | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Partial Response | 2 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Progressive Disease | 8 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Stable Disease | 3 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Complete Response | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Partial Response | 1 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Progressive Disease | 1 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Stable Disease | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Partial Response | NA Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Complete Response | NA Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Partial Response | 2 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Stable Disease | NA Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Progressive Disease | NA Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Stable Disease | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Progressive Disease | 2 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Complete Response | 2 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Progressive Disease | NA Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Progressive Disease | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Stable Disease | 1 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Complete Response | NA Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Partial Response | NA Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Stable Disease | NA Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Complete Response | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Partial Response | 2 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Progressive Disease | NA Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Stable Disease | NA Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Partial Response | NA Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | First Treatment - Complete Response | NA Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Complete Response | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Stable Disease | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Progressive Disease | 1 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Second Treatment - Partial Response | 1 Participants |
Primary
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Number of participants with Grades 3-5 treatment-related adverse events were compared in Arm 1N and Arm 1P; and adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Time frame: 30 days after end of treatment
Population: One participant was not treated on Arm 1N. Pre-specified by the protocol, there are two combined reporting groups for this outcome. The first combined group (n=23) is all who received standard chemo (Arm 1N, Arm 1P, the retreatment of Arm 2/1P, and the initial treatment of Arm 1P/R). The second combined group (n=12) is all who received the reduced dose chemo (Arm 2, and the initial treatment of Arm 2/1P) This separates reporting of adverse events by the intensity of chemotherapy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 1 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 1 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 1 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 4 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 2 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 2 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 2 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 3 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 2 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 2 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 1 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 2 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 2 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 1 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 2 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 1 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 2 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 4 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 3 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 1 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 4 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 1 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 6 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 1 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 1 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 1 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 1 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 2 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 1 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 2 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 1 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 1 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 1 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 11 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 14 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 1 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 14 Participants |
| Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 2 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 1 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 3 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 1 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 3 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 1 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 2 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 1 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 2 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 3 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 3 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 2 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 3 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 1 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 4 - Possibly Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 1 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 2 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 4 - Probably Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 4 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 2 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 9 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 4 - Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypotension | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Creatinine | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Confusion | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Phosphate, serum-low (hypophosphatemia) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hypoxia | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal failure | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Left ventricular systolic dysfunction | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Nausea | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Vomiting | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Allergic reaction/hypersensitivity (including drug fever) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Platelets | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Leukocytes (total WBC) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemoglobin | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Febrile neutropenia | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | AST, SGOT(serum glutamic oxaloacetic transaminase) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Renal/Genitourinary - Other (Specify, oliguria) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Diarrhea | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Weight loss | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Hemorrhage, GU::Vagina | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | PTT (Partial Thromboplastin Time) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Lymphopenia | 0 Participants |
Primary
Overall Response Rate (ORR)
Overall response is the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.0). Progression is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Date of cells until time of disease progression, up to approximately 67.2 months.
Population: Retreat Arm 1N and Arm 2 Foll By Arm 1P not treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Response Rate (ORR) | Initial Treatment | 23.10 percentage of participants |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Response Rate (ORR) | Retreat | 33.30 percentage of participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Response Rate (ORR) | Initial Treatment | 57.10 percentage of participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Response Rate (ORR) | Initial Treatment | 16.70 percentage of participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Response Rate (ORR) | Retreat | 50 percentage of participants |
Secondary
Number of Treatment-related Adverse Events for Participants Who Received Pembrolizumab
Number of treatment-related adverse events for participants who received pembrolizumab. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: Date treatment consent signed until approximately 4 weeks following last dose of Pembrolizumab, up to 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Treatment-related Adverse Events for Participants Who Received Pembrolizumab | 16 Adverse events |
Secondary
Overall Progression Free Survival (PFS)
PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Time to progression and time to death, approximately up to 67.2 months.
Population: 1/8 participants were not treated in Arm 1N.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Progression Free Survival (PFS) | 3 Months |
Secondary
Overall Survival
Overall survival is defined as the time from treatment start date until date of death, or date last known alive.
Time frame: Date of cells until time to death, up until 90.1 months.
Population: As pre-specified by the protocol, participants will be reported by the initial treatment arm: Arm 1N (n=7; 1/8 participants were not treated), Arm 1P (n=13), Arm 2 (n=12).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Survival | 14.3 Months |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Survival | NA Months |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Survival | 15.1 Months |
Secondary
Overall Survival
Overall survival is defined as the time from treatment start date until date of death, or date last known alive.
Time frame: An average of 25.6 months.
Population: 1/8 participants were not treated in Arm 1N.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Overall Survival | 17.5 Months |
Secondary
Progression-free Survival (PFS)
PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Date of cells until time of disease progression up to approximately 67.2 months.
Population: The first combined group (n=16) is Arm 1P, the second treatment of Arm 2/1P, the initial treatment of Arm 1P/R. The second group (n=7) is Arm 1N (1/8 participants was not treated). The third group (n=12) is Arm 2 and the initial treatment of Arm 2/1P. The final group (n=2) will report the second treatment of Arm 1P/R. This enables reporting of the 37 treatments among the 32 treated participants separated by exposure to pembrolizumab/nivolumab and chemo dose. 0 participants analyzed= not treated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Progression-free Survival (PFS) | Initial Treatment | 3.1 Months |
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Progression-free Survival (PFS) | Retreat | 1.6 Months |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Progression-free Survival (PFS) | Initial Treatment | 7.9 Months |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Progression-free Survival (PFS) | Initial Treatment | 2.1 Months |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Progression-free Survival (PFS) | Retreat | 32.5 Months |
Other Pre-specified
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
Population: 1/8 participants were not treated on Arm 1N.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 7 Participants |
| Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 9 Participants |
| Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 3 Participants |
| Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 9 Participants |
| Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 2 Participants |