Non-small Cell Lung Cancer
Conditions
Keywords
Non-small cell lung cancer, NSCLC, MEDI-575, Platelet-derived growth factor receptor alpha
Brief summary
The purpose of this study is to evaluate the dose, antitumor activity, safety and pharmacology of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer (NSCLC).
Detailed description
This is a Phase 1b/2, multicenter, open-label study of MEDI-575 to evaluate the dose, anti-tumor activity, safety, and pharmacology (pharmacokinetics, immunogenicity, and biomarkers) of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer. This study has two phases: dose determination (Phase 1b) and randomization (Phase 2).
Interventions
DRUGCarboplatin
Carboplatin (carboplatin area under the plasma concentration-time curve \[AUC\] of 6 milligram per milliliter into minute \[mg/mL\*min\] administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal.
DRUGPaclitaxel
Paclitaxel 200 milligram per square meter (mg/m\^2) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal.
DRUGMEDI-575
MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. MEDI-575 alone continued in those participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed inoperable Stage IIIB or Stage IV non-small cell lung cancer according to the Seventh Edition of the American Joint Committee on Cancer (AJCC) Tumor Node Metastases (TNM) staging system (only participants with squamous cell carcinoma will be enrolled) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy of greater than or equal to (\>=) 3 months * Prothrombin time elevation less than or equal to (\<=) Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) criteria (Version 4.0) is acceptable for participants on anticoagulant therapy * Adequate hematologic function * Adequate organ function * Suitable candidates for therapy with carboplatin/paclitaxel * Participants must have at least 1 lesion that is measurable using Response Evaluation Criteria for Solid Tumors * Participants must be willing to consent to allow collection of archived NSCLC tumor samples * Negative serum beta-human chorionic gonadotropin (beta-hCG) test (women of childbearing potential only) * Females of childbearing potential, unless surgically sterile has a sterile male partner, is premenarchal or at least 2 years postmenopausal, or practices abstinence, must use 2 effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) from screening, and must agree to continue using such precautions for 90 days after the final dose of treatment; cessation of birth control after this point should be discussed with a responsible physician * Males, unless surgically sterile, must use 2 effective methods of birth control with a female partner and must agree to continue using such contraceptive precautions from screening through 90 days after the final dose of treatment
Exclusion criteria
* At discretion of the investigator regarding safety of the participants * Concurrent enrollment in another clinical study * Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer * Previous monoclonal antibody (mAb) treatment specifically directed against platelet-derived growth factor (PDGF) or PDGF receptors * History of serious allergy or reaction to any component of the MEDI-575 formulation * Receipt of any previous systemic anticancer therapies for advanced or metastatic disease * Previous adjuvant/neoadjuvant radiotherapy or chemotherapy for treatment of previous nonmetastatic disease is allowed provided that 6 months have elapsed from the end of such therapies to the time of enrollment * New York Heart Association \>= Class II congestive heart failure * History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to enrollment * History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured * Evidence of active infection requiring the use of systemic antimicrobial treatment within 72 hours prior to initial treatment with MEDI-575 * Use of immunosuppressive medication (inhaled and topical corticosteroids are permitted) within 7 days prior to enrollment * Systemic immunosuppressive steroid therapy * Participants may take replacement doses of steroids if on a stable dose for at least 2 weeks prior to enrollment * History of active human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection * Pregnancy or lactation * Previous medical history or evidence of an inter-current illness * Any physical, social, or psychiatric condition which would prevent effective cooperation or participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b | From Day 1 to Day 21 of first cycle | A DLT was defined as: 1. Any treatment-related Grade 3 or higher non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: 1. Grade 3 fever (in the absence of neutropenia) defined as more than (\>) 40.0 degree Celcius (\> 104.0 degree Fahrenheit) that resolved to normal or baseline within 24 hours of treatment and was not considered a serious adverse event (SAE); or 2. Grade 3 rigors/chills that responded to optimal therapy. 2. Any treatment-related Grade 3 or higher hematologic toxicity. |
| Progression Free-Survival (PFS) | From randomization until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years) | Progression-free survival defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (defined according to Response Evaluation Criteria for Solid Tumors \[RECIST\] version 1.1 guidelines) or death due to any cause, whichever occurs first. Participants without progression or death at the time of analysis were censored at their last date of tumor evaluation. PFS was assessed only in North America/European Union (EU) participants. Progression-free survival was evaluated using Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response (TTR) | From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years) | The TTR was measured from initiation of study treatment to the first documentation of objective response (OR). The OR defined as the participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment \>=4 weeks after the initial documentation of response. The TTR was evaluated using Kaplan-Meier method. |
| Duration of Response (DR) | From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years) | The DR defined as the duration from the first documentation of OR to the first documented disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The DR was evaluated using Kaplan-Meier method. |
| Time to Progression (TTP) | From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years) | The TTP was measured from randomization until the documentation of disease progression. Disease progression defined according to RECIST version 1.1 guidelines. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The TTP was evaluated using Kaplan-Meier method. |
| Overall Survival (OS) | From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years) | Overall survival defined as the time from initiation of study treatment until death due to any cause. Participants who were still alive at the time of analysis were censored at their last date of last contact. The OS was evaluated using Kaplan-Meier method. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years) | Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs or SAEs were reported. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years) | The 12-lead ECG data were performed and obtained in triplicate that is 3 ECGs obtained within a 5 minute time period. Number of participants with ECG abnormalities were reported and recorded as AEs. |
| Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose | Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15 | The Cmax of MEDI-575 after first dose is reported. |
| Best Overall Response | From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years) | Best overall response of a participant was defined as the best tumor response \[Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)\] observed during the trial period assessed according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 criteria. The participant's best overall response assignment depended on the findings of both target and non-target disease and also on the appearance of new lesions. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30 percent (%) in the sum of diameters of target lesion, SD was defined as steady state of disease, and PD was defined as an increase of at least 20% in the sum of diameters of target lesions. |
| Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose | Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15 | The AUCtau defined as area under the plasma concentration time profile from time zero to the end of the dosing interval (tau). The AUCtau of MEDI-575 after first dose is reported. |
| Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575 | Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion) | The Cmax,ss of MEDI-575 is reported. |
| Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575 | Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion) | The Tmax,ss of MEDI-575 is reported. |
| Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575 | Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion) | The Ctrough,ss of MEDI-575 is reported. |
| Percentage of Participants With Positive Anti-MEDI-575 Antibodies | Day 1 (prior to infusion) of Cycles 1 to 7 (21-day cycle), end of treatment, 30 and 60 days after the last dose (approximately 3 years) | Immunogenicity assessment included determination of anti-drug (MEDI-575) antibodies in serum samples. |
| Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Baseline (Screening [Days -28 to -1]) | The immunohistochemical expression of PDGFRα in tumor cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining tumor cells are reported in 3 categories: intensity (1+ \[weak expression, staining in \<5 % of tumor cells\]; 2+ \[moderate expression, staining in \>= 5 % of tumor cells\]; and 3+ \[strong expression, staining in \>5 % of the tumor cells\]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent). |
| Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Baseline (Screening [Days -28 to -1]) | The immunohistochemical expression of PDGFRα in stromal cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining stromal cells are reported in 3 categories: intensity (1+ \[weak expression, staining in \<5 % of tumor cells\]; 2+ \[moderate expression, staining in \>= 5 % of tumor cells\]; and 3+ \[strong expression, staining in \>5 % of the tumor cells\]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent). |
| Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose | Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15 | The tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). The Tmax of MEDI-575 after first dose is reported. |
| Objective Response Rate (ORR) | From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years) | The ORR defined as the percentage of participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment greater than or equal to (\>=) 4 weeks after the initial documentation of response. The ORR was evaluated using Kaplan-Meier method. |
Countries
Canada, France, Germany, Hungary, Japan, Poland, United States
Participant flow
Pre-assignment details
Overall, 99 participants were enrolled in the study, (4 participants, all from North America sites, were enrolled in the Phase 1b part of the study and 95 participants in Phase 2 part of the study). Of 95 participants, 14 were enrolled from Japan sites, and 81 were from North American and European Union (EU) sites.
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin/Paclitaxel (C/P): North America/EU Population Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve \[AUC\] of 6 milligram per milliliter into minute \[mg/mL\*min\], and paclitaxel 200 milligram per square meter \[mg/m\^2\]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. | 40 |
| C/P + MEDI-575 (C/P/M): North America/EU Population Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL\*min, and paclitaxel 200 mg/m\^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. | 45 |
| Carboplatin/Paclitaxel (C/P): Japan Population Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL\*min, and paclitaxel 200 mg/m\^2) administered as an IV infusion once every 21 days on Day 1, for a total of 6 doses (cycles) or until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. | 6 |
| C/P + MEDI-575 (C/P/M): Japan Population Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL\*min, and paclitaxel 200 mg/m\^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles. Participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575, MEDI-575 alone was continued until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. | 8 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 20 | 30 | 3 | 5 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Progression of disease | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Carboplatin/Paclitaxel (C/P): North America/EU Population | C/P + MEDI-575 (C/P/M): North America/EU Population | Carboplatin/Paclitaxel (C/P): Japan Population | C/P + MEDI-575 (C/P/M): Japan Population |
|---|---|---|---|---|---|
| Age, Customized greater than (>) 70 years | 20 Participants | 5 Participants | 13 Participants | 0 Participants | 2 Participants |
| Age, Customized less than or equal to (<=) 70 years | 79 Participants | 35 Participants 6.6 | 32 Participants 8.2 | 6 Participants 13.9 | 6 Participants 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 39 Participants | 43 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 15 Participants | 0 Participants | 1 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 5 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 76 Participants | 37 Participants | 39 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 38 Participants | 17 Participants | 17 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 61 Participants | 23 Participants | 28 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 35 / 53 | 23 / 43 |
| other Total, other adverse events | 53 / 53 | 41 / 43 |
| serious Total, serious adverse events | 25 / 53 | 17 / 43 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b
A DLT was defined as: 1. Any treatment-related Grade 3 or higher non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: 1. Grade 3 fever (in the absence of neutropenia) defined as more than (\>) 40.0 degree Celcius (\> 104.0 degree Fahrenheit) that resolved to normal or baseline within 24 hours of treatment and was not considered a serious adverse event (SAE); or 2. Grade 3 rigors/chills that responded to optimal therapy. 2. Any treatment-related Grade 3 or higher hematologic toxicity.
Time frame: From Day 1 to Day 21 of first cycle
Population: The evaluable population for dose determination included all participants who were in Phase 1b, received at least 1 full cycle of MEDI-575 and completed the safety follow-up through the DLT evaluation period or participants who experienced any DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b | 0 Participants |
Primary
Progression Free-Survival (PFS)
Progression-free survival defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (defined according to Response Evaluation Criteria for Solid Tumors \[RECIST\] version 1.1 guidelines) or death due to any cause, whichever occurs first. Participants without progression or death at the time of analysis were censored at their last date of tumor evaluation. PFS was assessed only in North America/European Union (EU) participants. Progression-free survival was evaluated using Kaplan-Meier method.
Time frame: From randomization until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Population: The Intent-to-Treat (ITT) North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The PFS was analyzed for only those participants who had disease progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Progression Free-Survival (PFS) | 5.5 months |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Progression Free-Survival (PFS) | 4.6 months |
p-value: 0.02795% CI: [1.1, 4.5]Log Rank
Secondary
Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose
The AUCtau defined as area under the plasma concentration time profile from time zero to the end of the dosing interval (tau). The AUCtau of MEDI-575 after first dose is reported.
Time frame: Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
Population: Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses. Here Number of Participants Analyzed denotes the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose | 3550 microgram*day per milliliter | Standard Deviation 496.1 |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose | 4803 microgram*day per milliliter | Standard Deviation 1948 |
Secondary
Best Overall Response
Best overall response of a participant was defined as the best tumor response \[Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)\] observed during the trial period assessed according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 criteria. The participant's best overall response assignment depended on the findings of both target and non-target disease and also on the appearance of new lesions. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30 percent (%) in the sum of diameters of target lesion, SD was defined as steady state of disease, and PD was defined as an increase of at least 20% in the sum of diameters of target lesions.
Time frame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Population: The ITT North America/European Union (EU) population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Best Overall Response | Unknown | 7 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Best Overall Response | Partial response | 12 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Best Overall Response | Progressive disease | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Best Overall Response | Complete response | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Best Overall Response | Stable disease | 19 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Best Overall Response | Complete response | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Best Overall Response | Stable disease | 12 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Best Overall Response | Progressive disease | 5 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Best Overall Response | Partial response | 19 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Best Overall Response | Unknown | 5 Participants |
| Carboplatin/Paclitaxel - Japan | Best Overall Response | Progressive disease | 1 Participants |
| Carboplatin/Paclitaxel - Japan | Best Overall Response | Unknown | 0 Participants |
| Carboplatin/Paclitaxel - Japan | Best Overall Response | Partial response | 2 Participants |
| Carboplatin/Paclitaxel - Japan | Best Overall Response | Stable disease | 3 Participants |
| Carboplatin/Paclitaxel - Japan | Best Overall Response | Complete response | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Best Overall Response | Unknown | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Best Overall Response | Complete response | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Best Overall Response | Partial response | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Best Overall Response | Progressive disease | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Best Overall Response | Stable disease | 5 Participants |
Secondary
Duration of Response (DR)
The DR defined as the duration from the first documentation of OR to the first documented disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The DR was evaluated using Kaplan-Meier method.
Time frame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Population: The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study. Participants who achieved OR were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Duration of Response (DR) | 3.3 months |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Duration of Response (DR) | 4.2 months |
| Carboplatin/Paclitaxel - Japan | Duration of Response (DR) | 4.9 months |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Duration of Response (DR) | 2.1 months |
Secondary
Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose
The Cmax of MEDI-575 after first dose is reported.
Time frame: Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
Population: Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses. Here Number of Participants Analyzed denotes the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose | 589.3 microgram per milliliter | Standard Deviation 175.6 |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose | 628.9 microgram per milliliter | Standard Deviation 441.8 |
Secondary
Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575
The Cmax,ss of MEDI-575 is reported.
Time frame: Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
Population: Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses. Here Number of Participants Analyzed denotes the participants who received at least 4 doses of MEDI-575 and were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575 | 2997 microgram per milliliter | Standard Deviation 2588 |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575 | 619.7 microgram per milliliter | Standard Deviation 160.5 |
Secondary
Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs
Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs or SAEs were reported.
Time frame: From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
Population: The safety population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypomagnesaemia | 10 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hyponatraemia | 4 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypophosphataemia | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Iron deficiency | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Vitamin B12 deficiency | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Urine analysis abnormal | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Specific gravity urine increased | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Haematuria | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Proteinuria | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Pyelocaliectasis | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Gamma-glutamyl transferase increased | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Anaemia | 15 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Febrile neutropenia | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Idiopathic thrombocytopenic purpura | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Leukopenia | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Lymphadenopathy | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Lymphopenia | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Neutropenia | 7 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Thrombocytopenia | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Activated partial thromboplastin time prolonged | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Haemoglobin decreased | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Lymphocyte count decreased | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Neutrophil count decreased | 5 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Platelet count decreased | 5 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | White blood cell count decreased | 4 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Alanine aminotransferase increased | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Aspartate aminotransferase increased | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Blood alkaline phosphatase increased | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Blood bilirubin increased | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Blood creatinine increased | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Blood magnesium decreased | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Electrolyte imbalance | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypercholesterolaemia | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hyperglycaemia | 5 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypertriglyceridaemia | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypoalbuminaemia | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypocalcaemia | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypoglycaemia | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypokalemia | 8 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Activated partial thromboplastin time prolonged | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypomagnesaemia | 20 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Blood creatinine increased | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hyponatraemia | 8 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Haemoglobin decreased | 5 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypophosphataemia | 4 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypertriglyceridaemia | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Iron deficiency | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Lymphocyte count decreased | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Vitamin B12 deficiency | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Blood magnesium decreased | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Urine analysis abnormal | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Neutrophil count decreased | 14 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Specific gravity urine increased | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypokalemia | 12 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Haematuria | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Platelet count decreased | 9 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Proteinuria | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Electrolyte imbalance | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Pyelocaliectasis | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | White blood cell count decreased | 10 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Gamma-glutamyl transferase increased | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypoalbuminaemia | 7 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Anaemia | 25 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Alanine aminotransferase increased | 5 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Febrile neutropenia | 6 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypercholesterolaemia | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Idiopathic thrombocytopenic purpura | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Aspartate aminotransferase increased | 4 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Leukopenia | 6 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypoglycaemia | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Lymphadenopathy | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Blood alkaline phosphatase increased | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Lymphopenia | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hyperglycaemia | 7 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Neutropenia | 13 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Blood bilirubin increased | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Thrombocytopenia | 10 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs | Hypocalcaemia | 6 Participants |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
Population: The safety population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 42 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 17 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 53 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 25 Participants |
Secondary
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs
The 12-lead ECG data were performed and obtained in triplicate that is 3 ECGs obtained within a 5 minute time period. Number of participants with ECG abnormalities were reported and recorded as AEs.
Time frame: From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
Population: The safety population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Tachycardia | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Atrial fibrillation | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Atrial flutter | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Atrioventricular block first degree | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Myocardial infarction | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Myocardial infarction | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Atrioventricular block first degree | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Atrial fibrillation | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Tachycardia | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs | Atrial flutter | 1 Participants |
Secondary
Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples
The immunohistochemical expression of PDGFRα in stromal cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining stromal cells are reported in 3 categories: intensity (1+ \[weak expression, staining in \<5 % of tumor cells\]; 2+ \[moderate expression, staining in \>= 5 % of tumor cells\]; and 3+ \[strong expression, staining in \>5 % of the tumor cells\]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent).
Time frame: Baseline (Screening [Days -28 to -1])
Population: Evaluable populations for PDGFRα expression included all randomized participants who had formalin-fixed paraffin-embedded samples available at baseline and had positive-staining for tumor cells.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Localization: cytoplasmic | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Frequency: frequent | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Localization: nuclear | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Localization: membranous | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Intensity: 1+ | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Frequency: occasional | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Intensity: 3+ | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Intensity: 2+ | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Frequency: rare | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Localization: membranous | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Intensity: 1+ | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Intensity: 2+ | 10 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Intensity: 3+ | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Localization: cytoplasmic | 15 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Localization: nuclear | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Frequency: rare | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Frequency: occasional | 4 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Frequency: frequent | 9 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Intensity: 3+ | 2 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Intensity: 1+ | 3 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Frequency: rare | 1 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Intensity: 2+ | 5 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Frequency: frequent | 6 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Localization: membranous | 0 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Localization: cytoplasmic | 10 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Frequency: occasional | 3 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples | Localization: nuclear | 0 Participants |
Secondary
Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples
The immunohistochemical expression of PDGFRα in tumor cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining tumor cells are reported in 3 categories: intensity (1+ \[weak expression, staining in \<5 % of tumor cells\]; 2+ \[moderate expression, staining in \>= 5 % of tumor cells\]; and 3+ \[strong expression, staining in \>5 % of the tumor cells\]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent).
Time frame: Baseline (Screening [Days -28 to -1])
Population: Evaluable populations for PDGFRα expression included all randomized participants who had formalin-fixed paraffin-embedded samples available at baseline and had positive-staining for tumor cells.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Localization: cytoplasmic | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Frequency: frequent | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Localization: nuclear | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Localization: membranous | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Intensity: 1+ | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Frequency: occasional | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Intensity: 3+ | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Intensity: 2+ | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Frequency: rare | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Localization: membranous | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Intensity: 1+ | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Intensity: 2+ | 2 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Intensity: 3+ | 1 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Localization: cytoplasmic | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Localization: nuclear | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Frequency: rare | 3 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Frequency: occasional | 0 Participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Frequency: frequent | 2 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Intensity: 3+ | 0 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Intensity: 1+ | 3 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Frequency: rare | 1 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Intensity: 2+ | 0 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Frequency: frequent | 1 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Localization: membranous | 0 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Localization: cytoplasmic | 2 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Frequency: occasional | 1 Participants |
| Carboplatin/Paclitaxel - Japan | Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples | Localization: nuclear | 1 Participants |
Secondary
Objective Response Rate (ORR)
The ORR defined as the percentage of participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment greater than or equal to (\>=) 4 weeks after the initial documentation of response. The ORR was evaluated using Kaplan-Meier method.
Time frame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Population: The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Objective Response Rate (ORR) | 22.5 percentage of participants |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Objective Response Rate (ORR) | 31.7 percentage of participants |
| Carboplatin/Paclitaxel - Japan | Objective Response Rate (ORR) | 33.3 percentage of participants |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Objective Response Rate (ORR) | 12.5 percentage of participants |
Comparison: Treatment effect Carboplatin/Paclitaxel + MEDI-575 versus Carboplatin/Paclitaxel.p-value: 0.487Cochran-Mantel-Haenszel
Comparison: Treatment effect Carboplatin/Paclitaxel + MEDI-575 versus Carboplatin/Paclitaxel.p-value: 0.386Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS)
Overall survival defined as the time from initiation of study treatment until death due to any cause. Participants who were still alive at the time of analysis were censored at their last date of last contact. The OS was evaluated using Kaplan-Meier method.
Time frame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Population: The ITT North America/EU population and the ITT Japanese population included all participants who were randomized into the Phase 2 portion of the study. The Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Overall Survival (OS) | 11.8 months |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Overall Survival (OS) | 10.0 months |
| Carboplatin/Paclitaxel - Japan | Overall Survival (OS) | NA months |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Overall Survival (OS) | 11.5 months |
95% CI: [0.7, 2.4]
95% CI: [0.4, 10.8]
Secondary
Percentage of Participants With Positive Anti-MEDI-575 Antibodies
Immunogenicity assessment included determination of anti-drug (MEDI-575) antibodies in serum samples.
Time frame: Day 1 (prior to infusion) of Cycles 1 to 7 (21-day cycle), end of treatment, 30 and 60 days after the last dose (approximately 3 years)
Population: The evaluable population included all participants who were treated with MEDI-575 and for whom at least one serum sample for immunogenicity testing was available.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Percentage of Participants With Positive Anti-MEDI-575 Antibodies | 25.0 percentage of participants | 496.1 |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Percentage of Participants With Positive Anti-MEDI-575 Antibodies | 26.5 percentage of participants | 1948 |
Secondary
Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose
The tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). The Tmax of MEDI-575 after first dose is reported.
Time frame: Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
Population: Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses. Here Number of Participants Analyzed denotes the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose | 0.044 day | Standard Deviation 0.002 |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose | 0.046 day | Standard Deviation 0.009 |
Secondary
Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575
The Tmax,ss of MEDI-575 is reported.
Time frame: Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
Population: Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses. Here Number of Participants Analyzed denotes the participants who received at least 4 doses of MEDI-575 and were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575 | 0.042 day | Standard Deviation 0 |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575 | 0.049 day | Standard Deviation 0.017 |
Secondary
Time to Progression (TTP)
The TTP was measured from randomization until the documentation of disease progression. Disease progression defined according to RECIST version 1.1 guidelines. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The TTP was evaluated using Kaplan-Meier method.
Time frame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Population: The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study. The TTP was analyzed for only those participants who had disease progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Time to Progression (TTP) | 6.4 months |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Time to Progression (TTP) | 4.6 months |
| Carboplatin/Paclitaxel - Japan | Time to Progression (TTP) | 6.5 months |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Time to Progression (TTP) | 4.6 months |
95% CI: [1.2, 7.4]
95% CI: [0.3, 4.3]
Secondary
Time to Response (TTR)
The TTR was measured from initiation of study treatment to the first documentation of objective response (OR). The OR defined as the participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment \>=4 weeks after the initial documentation of response. The TTR was evaluated using Kaplan-Meier method.
Time frame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Population: The ITT North America/EU population included all North America/EU participants who were randomized into Phase 2 portion of the study. The ITT Japanese population included all Japanese participants who were randomized into the Phase 2 portion of the study. Participants who achieved OR were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Time to Response (TTR) | 1.4 months |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Time to Response (TTR) | 1.4 months |
| Carboplatin/Paclitaxel - Japan | Time to Response (TTR) | 2.2 months |
| Carboplatin/Paclitaxel + MEDI-575 - Japan | Time to Response (TTR) | 2.8 months |
Secondary
Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575
The Ctrough,ss of MEDI-575 is reported.
Time frame: Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
Population: Participants who were treated with MEDI-575 and for whom serum concentrations were available for PK data analyses. Here Number of Participants Analyzed denotes the participants who received at least 4 doses of MEDI-575 and were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carboplatin/Paclitaxel + MEDI-575 - Phase 1b | Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575 | 375 microgram per milliliter | Standard Deviation 155 |
| Carboplatin/Paclitaxel + MEDI-575 - North America/EU | Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575 | 168 microgram per milliliter | Standard Deviation 75.6 |