Adenocarcinoma, Breast Cancer, Carcinoma, Non-Small-Cell Lung, Colorectal Cancer, Pancreatic Cancer
Conditions
Brief summary
This study is a Phase I, first in human, dose-escalation study of MORAb-066, an investigational humanized immunoglobulin G (IgG) monoclonal antibody (mAb) that targets TF-expressing malignancies that include breast, pancreatic, colorectal, and non-small-cell lung cancer (NSCLC) (adenocarcinoma). This open-label study will assess the safety, tolerability, and pharmacokinetics of MORAb-066 administered weekly. This study will identify the maximum tolerated dose (MTD) when MORAb-066 is administered IV once weekly on a 28-day cycle.
Interventions
DRUGMORAb-066
MORAb-066 infusion.
Sponsors
SCRI Development Innovations, LLC
Morphotek
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
Patients must meet the following criteria in order to be included in this clinical trial: 1. Histologically or cytologically confirmed diagnosis of breast, colorectal, pancreas, or NSCLC (adenocarcinoma) that is metastatic or unresectable for which there is no effective therapy. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 (see Appendix A). 3. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 4. Subject has recovered (to Grade less than or equal to 1) from all clinically significant toxicities related to prior antineoplastic therapies with the exception of alopecia and bone marrow and organ functions (described separately below). 5. Adequate organ system function less than or equal to 2 weeks prior to Day1, defined as follows: * Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10\^9/L * Platelets greater than or equal to 100 x 10\^9/L * Hemoglobin greater than or equal to 9 g/dL * Prothrombin time/partial thromboplastin time (PT/PTT) within institutional limits of normal * Serum total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3.0 x ULN if no liver involvement or less than or equal to 5 x ULN with liver involvement. * Serum creatinine less than or equal to 1.5 x ULN or calculated creatinine clearance greater than or equal to 50 mL/min as calculated by the Cockcroft-Gault method, OR 24-hour measured urine creatinine clearance greater than or equal to 50 mL/min. 6. Life expectancy of greater than or equal to 12 weeks. 7. Female patients of child-bearing potential (see Appendix C), and all male patients must consent to use a medically acceptable method of contraception throughout the study period and for 30 days after their last MORAb-066 administration. A barrier method of contraception must be included. 8. Patients must be greater than or equal to 18 years of age. 9. Patients entering this study will be asked to provide archival tissue from a previous tumor biopsy (if available) for correlative testing. If tissue is not available, the subject will still be eligible for enrollment into the study. 10. Ability to understand the nature of this study and give written informed consent.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from trial entry: 1. Patients currently receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization). 2. Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of MORAb-066. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of MORAb-066 is required. 3. Any major surgery, chemotherapy, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed greater than or equal to 2 weeks). 4. Subject has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) less than or equal to 28 days or limited field radiation for palliation less than or equal to 14 days prior to starting study drug or has not recovered from side effects of such therapy. 5. Known intracranial involvement, leptomeningeal metastases or spinal cord compression due to disease. 6. Known allergy or hypersensitivity to monoclonal antibodies. 7. Known bleeding diathesis, such as factor deficiency, factor inhibitor, platelet disorder, or who are on active anticoagulation, or any dose of aspirin within 5 days prior to first dose of MORAb-066. 8. Known prior significant bleeding history. 9. Patients with ureteral stents or 3+ blood in the urine at baseline. 10. Patients who are receiving chronic systemic anticoagulation therapy (warfarin sodium or heparin, etc.). 11. Patients who received a previous mAb therapy and have evidence of an immune or allergic reaction or previously documented HAHA reaction. 12. A serious non-healing wound, active ulcer, or untreated bone fracture. An abdominal fistula or gastrointestinal perforation less than 6 months prior to treatment. 13. History of hematemesis or hemoptysis (defined as having bright red blood of 1/2 teaspoon or more per episode) less than or equal to 1 month prior to study enrollment. 14. Subject has cardiac dysfunction including any of the following: * Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction function * QTcF greater than 470 msec * History of documented congestive heart failure (New York Heart Association functional classification III-IV \[see Appendix B\]) * Angina not well-controlled by medication 15. A serious active infection (bacterial or fungal) at the time of treatment, or another serious underlying medical condition that would impair the ability of the subject to receive protocol treatment. 16. Chronic inflammatory disorder(e.g., inflammatory bowel disease, active vasculitis). 17. Herbal preparations/medications must be discontinued 7 days prior to first dose of study drug (see Section 5.3.1). 18. Known diagnosis of human immunodeficiency virus, Hepatitis B or Hepatitis C. 19. History or current diagnosis of glomerulonephritis 20. History of clinically significant or current diagnosis of hematuria. 21. Women who are pregnant or lactating. 22. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 23. Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol. 24. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | First dose of study drug (Baseline) up to 30 days after last dose of study drug (Up to approximately 2 years 7 months) | Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood chemistry, urine values, and vital signs; periodic measurement of electrocardiograms (ECGs) and Eastern Cooperative Oncology Group (ECOG) assessments; and performance of physical examinations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Cycle 1 (Cycle length=28 days) | The MTD was defined as the highest dose level at which no more than one out of six participants experienced DLT. DLT was defined using NCI CTCAE Version 4.03 as any grade 3 or 4 hematemesis, hemoptysis, hematochezia, bright red blood per rectum, epistaxis, gingival bleeding, hemarthrosis, haematuria, uncontrollable menses, or any other bleeding thought to be significant as per assessment of the investigator, regardless of grade. |
| Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days) | — |
| Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days) | — |
| t1/2: Terminal Elimination Phase Half-Life for MORAb-066 | Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days) | — |
| AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days) | — |
| Number of Participants With Dose Limiting Toxicity (DLT) | Cycle 1 (Cycle length=28 days) | DLT was defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 as any grade 3 or 4 hematemesis, hemoptysis, hematochezia, bright red blood per rectum, epistaxis, gingival bleeding, hemarthrosis, haematuria, uncontrollable menses, or any other bleeding thought to be significant as per assessment of the investigator, regardless of grade. |
| Vd: Volume of Distribution for MORAb-066 | Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days) | — |
| CL: Total Body Clearance for MORAb-066 | Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days) | — |
| Number of Participants With Best Overall Response (BOR) | Up to approximately 2 years 7 months | BOR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for target and non-target lesions is complete response (CR) or partial response (PR). CR: disappearance of target and non-target lesions, normalization of tumor marker level, all lymph nodes must be non-pathological in size (less than 10 millimeter \[mm\] short axis). PR: at least 30 percent (%) decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Number of Participants Positive for Antidrug Antibodies (ADA) | Up to approximately 2 years 7 months | — |
| AUC(0-Inf): Area Under the Serum Concentration-time Curve From Zero to Infinity for MORAb-066 | Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days) | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 2 investigative sites in the United States from 19 June 2013 to 09 February 2016.
Pre-assignment details
A total of 27 participants were enrolled and treated in the study.
Participants by arm
| Arm | Count |
|---|---|
| MORAb-066 0.1 mg/kg Participants received MORAb-066 0.1 mg/kg, infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, participant's discontinuation due to unacceptable toxicity, withdrawal by participants, or discontinuation by study physician decision. | 3 |
| MORAb-066 0.3 mg/kg Participants received MORAb-066 0.3 mg/kg, infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, the participant discontinuation due to unacceptable toxicity, withdrawal by participants, or discontinuation by study physician decision. | 4 |
| MORAb-066 1 mg/kg Participants received MORAb-066 1 mg/kg, infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, the participant's discontinuation due to unacceptable toxicity, withdrawal by participants, or discontinuation by study physician decision. | 5 |
| MORAb-066 2 mg/kg Participants received MORAb-066 2 mg/kg, infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, the participant's discontinuation due to unacceptable toxicity, withdrawal by participants, or discontinuation by study physician decision. | 7 |
| MORAb-066 3 mg/kg Participants received MORAb-066 3 mg/kg, infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, the participant discontinuation due to unacceptable toxicity, withdrawal by participants, or discontinuation by study physician decision. | 8 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 6 |
| Overall Study | Death | 0 | 1 | 1 | 2 | 1 |
| Overall Study | Non-compliance | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Progressive disease:clinical assessment | 0 | 0 | 3 | 1 | 0 |
| Overall Study | Progressive disease:radiology assessment | 3 | 3 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | MORAb-066 0.1 mg/kg | MORAb-066 0.3 mg/kg | MORAb-066 1 mg/kg | MORAb-066 2 mg/kg | MORAb-066 3 mg/kg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 7.21 | 57.8 years STANDARD_DEVIATION 9.39 | 55.2 years STANDARD_DEVIATION 6.06 | 62.4 years STANDARD_DEVIATION 7.98 | 64.3 years STANDARD_DEVIATION 8.75 | 60.8 years STANDARD_DEVIATION 8.18 |
| 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 | 3 Participants | 3 Participants | 5 Participants | 6 Participants | 7 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 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 | 2 Participants | 1 Participants | 0 Participants | 3 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 | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 2 Participants | 5 Participants | 8 Participants | 22 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 15 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 4 Participants | 12 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 | 0 / 3 | 1 / 4 | 1 / 5 | 2 / 7 | 1 / 8 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 5 / 5 | 7 / 7 | 8 / 8 |
| serious Total, serious adverse events | 0 / 3 | 1 / 4 | 3 / 5 | 4 / 7 | 3 / 8 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood chemistry, urine values, and vital signs; periodic measurement of electrocardiograms (ECGs) and Eastern Cooperative Oncology Group (ECOG) assessments; and performance of physical examinations.
Time frame: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Up to approximately 2 years 7 months)
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MORAb-066 0.1 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| MORAb-066 0.1 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| MORAb-066 0.3 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 4 Participants |
| MORAb-066 0.3 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| MORAb-066 1 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 5 Participants |
| MORAb-066 1 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 3 Participants |
| MORAb-066 2 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 4 Participants |
| MORAb-066 2 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| MORAb-066 3 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 8 Participants |
| MORAb-066 3 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 3 Participants |
Secondary
AUC(0-Inf): Area Under the Serum Concentration-time Curve From Zero to Infinity for MORAb-066
Time frame: Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Population: The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. Here,Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, Number analyzed signifies participants evaluable at a given time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MORAb-066 0.3 mg/kg | AUC(0-Inf): Area Under the Serum Concentration-time Curve From Zero to Infinity for MORAb-066 | Cycle 1 Day 1 | 249 hour*microgram per milliliter | Standard Deviation 4.2 |
| MORAb-066 0.3 mg/kg | AUC(0-Inf): Area Under the Serum Concentration-time Curve From Zero to Infinity for MORAb-066 | Cycle 1 Day 22 | 227 hour*microgram per milliliter | — |
| MORAb-066 1 mg/kg | AUC(0-Inf): Area Under the Serum Concentration-time Curve From Zero to Infinity for MORAb-066 | Cycle 1 Day 1 | 1569 hour*microgram per milliliter | Standard Deviation 707.9 |
| MORAb-066 1 mg/kg | AUC(0-Inf): Area Under the Serum Concentration-time Curve From Zero to Infinity for MORAb-066 | Cycle 1 Day 22 | 1410 hour*microgram per milliliter | — |
| MORAb-066 2 mg/kg | AUC(0-Inf): Area Under the Serum Concentration-time Curve From Zero to Infinity for MORAb-066 | Cycle 1 Day 1 | 4210 hour*microgram per milliliter | — |
| MORAb-066 3 mg/kg | AUC(0-Inf): Area Under the Serum Concentration-time Curve From Zero to Infinity for MORAb-066 | Cycle 1 Day 1 | 5970 hour*microgram per milliliter | — |
Secondary
AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066
Time frame: Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Population: The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, Number analyzed signifies participants evaluable at a given time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MORAb-066 0.1 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 1 | 95.5 hours*microgram/milliliter | Standard Deviation 44.92 |
| MORAb-066 0.1 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 22 | 61.2 hours*microgram/milliliter | Standard Deviation 25.09 |
| MORAb-066 0.3 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 1 | 202.3 hours*microgram/milliliter | Standard Deviation 41.48 |
| MORAb-066 0.3 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 22 | 188.5 hours*microgram/milliliter | Standard Deviation 51.62 |
| MORAb-066 1 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 1 | 1535.6 hours*microgram/milliliter | Standard Deviation 589.97 |
| MORAb-066 1 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 22 | 1541.3 hours*microgram/milliliter | Standard Deviation 1245.66 |
| MORAb-066 2 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 22 | 5188.0 hours*microgram/milliliter | Standard Deviation 1911.22 |
| MORAb-066 2 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 1 | 2415.5 hours*microgram/milliliter | Standard Deviation 1245.84 |
| MORAb-066 3 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 1 | 4536.3 hours*microgram/milliliter | Standard Deviation 1104.35 |
| MORAb-066 3 mg/kg | AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066 | Cycle 1 Day 22 | 10420.0 hours*microgram/milliliter | Standard Deviation 1244.51 |
Secondary
CL: Total Body Clearance for MORAb-066
Time frame: Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Population: The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, Number analyzed signifies participants evaluable at a given time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MORAb-066 0.3 mg/kg | CL: Total Body Clearance for MORAb-066 | Cycle 1 Day 1 | 0.1048 liter per hour | Standard Deviation 0.05268 |
| MORAb-066 0.3 mg/kg | CL: Total Body Clearance for MORAb-066 | Cycle 1 Day 22 | 0.1060 liter per hour | — |
| MORAb-066 1 mg/kg | CL: Total Body Clearance for MORAb-066 | Cycle 1 Day 1 | 0.0516 liter per hour | Standard Deviation 0.00894 |
| MORAb-066 1 mg/kg | CL: Total Body Clearance for MORAb-066 | Cycle 1 Day 22 | 0.0396 liter per hour | — |
| MORAb-066 2 mg/kg | CL: Total Body Clearance for MORAb-066 | Cycle 1 Day 1 | 0.0362 liter per hour | — |
| MORAb-066 3 mg/kg | CL: Total Body Clearance for MORAb-066 | Cycle 1 Day 1 | 0.0488 liter per hour | — |
Secondary
Cmax: Maximum Observed Serum Concentration for MORAb-066
Time frame: Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Population: The pharmacokinetic (PK) analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. Here, Number analyzed signifies participants evaluable at a given time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MORAb-066 0.1 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 2.09 microgram per milliliter (mcg/mL) | Standard Deviation 0.186 |
| MORAb-066 0.1 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 1.95 microgram per milliliter (mcg/mL) | Standard Deviation 0.731 |
| MORAb-066 0.3 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 5.26 microgram per milliliter (mcg/mL) | Standard Deviation 0.826 |
| MORAb-066 0.3 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 4.33 microgram per milliliter (mcg/mL) | Standard Deviation 0.014 |
| MORAb-066 1 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 23.40 microgram per milliliter (mcg/mL) | Standard Deviation 5.697 |
| MORAb-066 1 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 21.33 microgram per milliliter (mcg/mL) | Standard Deviation 7.106 |
| MORAb-066 2 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 52.68 microgram per milliliter (mcg/mL) | Standard Deviation 12.544 |
| MORAb-066 2 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 45.65 microgram per milliliter (mcg/mL) | Standard Deviation 12.37 |
| MORAb-066 3 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 68.61 microgram per milliliter (mcg/mL) | Standard Deviation 13.201 |
| MORAb-066 3 mg/kg | Cmax: Maximum Observed Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 121.50 microgram per milliliter (mcg/mL) | Standard Deviation 30.406 |
Secondary
Maximum Tolerated Dose (MTD)
The MTD was defined as the highest dose level at which no more than one out of six participants experienced DLT. DLT was defined using NCI CTCAE Version 4.03 as any grade 3 or 4 hematemesis, hemoptysis, hematochezia, bright red blood per rectum, epistaxis, gingival bleeding, hemarthrosis, haematuria, uncontrollable menses, or any other bleeding thought to be significant as per assessment of the investigator, regardless of grade.
Time frame: Cycle 1 (Cycle length=28 days)
Population: The DLT evaluable set included all participants who were evaluable for the DLTs in first cycle and had taken at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MORAb-066 0.1 mg/kg | Maximum Tolerated Dose (MTD) | 2 mg/kg |
Secondary
Number of Participants Positive for Antidrug Antibodies (ADA)
Time frame: Up to approximately 2 years 7 months
Population: The ADA evaluable population was the participants who received at least one dose of study drug and had at least one post-baseline ADA sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MORAb-066 0.1 mg/kg | Number of Participants Positive for Antidrug Antibodies (ADA) | 1 Participants |
| MORAb-066 0.3 mg/kg | Number of Participants Positive for Antidrug Antibodies (ADA) | 0 Participants |
| MORAb-066 1 mg/kg | Number of Participants Positive for Antidrug Antibodies (ADA) | 2 Participants |
| MORAb-066 2 mg/kg | Number of Participants Positive for Antidrug Antibodies (ADA) | 1 Participants |
| MORAb-066 3 mg/kg | Number of Participants Positive for Antidrug Antibodies (ADA) | 1 Participants |
Secondary
Number of Participants With Best Overall Response (BOR)
BOR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for target and non-target lesions is complete response (CR) or partial response (PR). CR: disappearance of target and non-target lesions, normalization of tumor marker level, all lymph nodes must be non-pathological in size (less than 10 millimeter \[mm\] short axis). PR: at least 30 percent (%) decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: Up to approximately 2 years 7 months
Population: The efficacy analysis set was the group of participants who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MORAb-066 0.1 mg/kg | Number of Participants With Best Overall Response (BOR) | Stable Disease | 0 Participants |
| MORAb-066 0.1 mg/kg | Number of Participants With Best Overall Response (BOR) | Not Assessed | 0 Participants |
| MORAb-066 0.1 mg/kg | Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| MORAb-066 0.3 mg/kg | Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| MORAb-066 0.3 mg/kg | Number of Participants With Best Overall Response (BOR) | Stable Disease | 0 Participants |
| MORAb-066 0.3 mg/kg | Number of Participants With Best Overall Response (BOR) | Not Assessed | 1 Participants |
| MORAb-066 1 mg/kg | Number of Participants With Best Overall Response (BOR) | Progressive Disease | 2 Participants |
| MORAb-066 1 mg/kg | Number of Participants With Best Overall Response (BOR) | Stable Disease | 0 Participants |
| MORAb-066 1 mg/kg | Number of Participants With Best Overall Response (BOR) | Not Assessed | 3 Participants |
| MORAb-066 2 mg/kg | Number of Participants With Best Overall Response (BOR) | Stable Disease | 0 Participants |
| MORAb-066 2 mg/kg | Number of Participants With Best Overall Response (BOR) | Not Assessed | 4 Participants |
| MORAb-066 2 mg/kg | Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| MORAb-066 3 mg/kg | Number of Participants With Best Overall Response (BOR) | Progressive Disease | 1 Participants |
| MORAb-066 3 mg/kg | Number of Participants With Best Overall Response (BOR) | Stable Disease | 1 Participants |
| MORAb-066 3 mg/kg | Number of Participants With Best Overall Response (BOR) | Not Assessed | 6 Participants |
Secondary
Number of Participants With Dose Limiting Toxicity (DLT)
DLT was defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 as any grade 3 or 4 hematemesis, hemoptysis, hematochezia, bright red blood per rectum, epistaxis, gingival bleeding, hemarthrosis, haematuria, uncontrollable menses, or any other bleeding thought to be significant as per assessment of the investigator, regardless of grade.
Time frame: Cycle 1 (Cycle length=28 days)
Population: The DLT evaluable set included all participants who were evaluable for the DLTs in first cycle and had taken at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MORAb-066 0.1 mg/kg | Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |
| MORAb-066 0.3 mg/kg | Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |
| MORAb-066 1 mg/kg | Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |
| MORAb-066 2 mg/kg | Number of Participants With Dose Limiting Toxicity (DLT) | 1 Participants |
| MORAb-066 3 mg/kg | Number of Participants With Dose Limiting Toxicity (DLT) | 3 Participants |
Secondary
t1/2: Terminal Elimination Phase Half-Life for MORAb-066
Time frame: Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Population: The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, Number analyzed signifies participants evaluable at a given time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MORAb-066 0.3 mg/kg | t1/2: Terminal Elimination Phase Half-Life for MORAb-066 | Cycle 1 Day 1 | 30.8 hours | Standard Deviation 10.68 |
| MORAb-066 0.3 mg/kg | t1/2: Terminal Elimination Phase Half-Life for MORAb-066 | Cycle 1 Day 22 | 24.1 hours | — |
| MORAb-066 1 mg/kg | t1/2: Terminal Elimination Phase Half-Life for MORAb-066 | Cycle 1 Day 1 | 52.2 hours | Standard Deviation 10.22 |
| MORAb-066 1 mg/kg | t1/2: Terminal Elimination Phase Half-Life for MORAb-066 | Cycle 1 Day 22 | 44.6 hours | — |
| MORAb-066 2 mg/kg | t1/2: Terminal Elimination Phase Half-Life for MORAb-066 | Cycle 1 Day 1 | 80.2 hours | — |
| MORAb-066 3 mg/kg | t1/2: Terminal Elimination Phase Half-Life for MORAb-066 | Cycle 1 Day 1 | 57.1 hours | — |
Secondary
Tmax: Time to Reach Maximum Serum Concentration for MORAb-066
Time frame: Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Population: The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. Here, Number analyzed signifies participants evaluable at a given time points for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MORAb-066 0.1 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 1.28 hours |
| MORAb-066 0.1 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 1.33 hours |
| MORAb-066 0.3 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 1.30 hours |
| MORAb-066 0.3 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 1.25 hours |
| MORAb-066 1 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 1.25 hours |
| MORAb-066 1 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 1.25 hours |
| MORAb-066 2 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 1.92 hours |
| MORAb-066 2 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 1.80 hours |
| MORAb-066 3 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 1 | 1.82 hours |
| MORAb-066 3 mg/kg | Tmax: Time to Reach Maximum Serum Concentration for MORAb-066 | Cycle 1 Day 22 | 1.77 hours |
Secondary
Vd: Volume of Distribution for MORAb-066
Time frame: Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Population: The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, Number analyzed signifies participants evaluable at a given time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MORAb-066 0.3 mg/kg | Vd: Volume of Distribution for MORAb-066 | Cycle 1 Day 1 | 5.06 liter | Standard Deviation 3.96 |
| MORAb-066 0.3 mg/kg | Vd: Volume of Distribution for MORAb-066 | Cycle 1 Day 22 | 3.68 liter | — |
| MORAb-066 1 mg/kg | Vd: Volume of Distribution for MORAb-066 | Cycle 1 Day 1 | 3.89 liter | Standard Deviation 1.029 |
| MORAb-066 1 mg/kg | Vd: Volume of Distribution for MORAb-066 | Cycle 1 Day 22 | 2.55 liter | — |
| MORAb-066 2 mg/kg | Vd: Volume of Distribution for MORAb-066 | Cycle 1 Day 1 | 3.88 liter | — |
| MORAb-066 3 mg/kg | Vd: Volume of Distribution for MORAb-066 | Cycle 1 Day 1 | 4.01 liter | — |