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| ID | Type | Description | Link |
|---|---|---|---|
| DEK-DKK1-P100 | Other Identifier | Healthcare Pharmaceuticals | |
| LY2812176 | Other Identifier | Healthcare Pharmaceuticals |
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The purpose of this trial is to characterize the safety and toxicity of DKN-01 by determining a maximum-tolerated dose and associated dose limiting toxicity. To evaluate the pharmacodynamic response in patients with cancer. To characterize the pharmacokinetic parameters of DKN-01 in cancer patients who are intolerant to standard/approved therapies.
Part A of this trial consists of 4 treatment arms of DKN-01. It is a dose escalation study in patients with multiple myeloma or advanced solid tumors. Patients must be refractory or intolerant to all standard/approved therapy(ies). At each dose level, 3 subjects will be treated. If none of the 3 subjects develop a dose limiting toxicity after a minimum of 4 weeks of treatment, subsequent dose escalation will proceed according to the same schedule. Part B consists of dose confirmation in patients with NSCLC. Patients must be refractory or intolerant to all standard/approved therapy(ies). Approximately 15 patients may be enrolled in Part B.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 75 milligram (mg) DKN-01 Part A | Experimental | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
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| 150 mg DKN-01 Part A | Experimental | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
|
| 300 mg DKN-01 Part A | Experimental | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DKN-01 | Drug | DKN-01 will be administered intravenously (IV) once a week over 30 minutes (min) and 2 hours (max) for 75, 150 and 300 mg. At 600 mg, DKN-01 will be administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: 3 participants will be treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation will occur sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching maximum tolerated dose (MTD) are met (or highest planned dose study group is completed). Cycle 1 will define the dose limiting toxicity (DLT) that governs dose escalation. PART B - Dose Confirmation: Once the MTD is established (or the highest planned dose level), 300 mg of DKN-01 will be administered IV on days 1 and 15 of every 28 day cycle. |
| Measure | Description | Time Frame |
|---|---|---|
| Summary of Total Adverse Events (AE) | Total Adverse Events (AE), total treatment emergent adverse events (TEAE), total Serious Adverse Events (SAE), and total dose-limiting toxicity (DLT) for both Parts A and B. | Baseline to study completion (approximately 3 months) |
| Summary of Patients With Adverse Events (AE) | Number of patients who had Adverse Events (AE) including treatment related treatment emergent adverse events (TEAE), Common Toxicity Criteria for Adverse Effects (CTCAE), and Serious Adverse Events (SAE) for both Parts A and B. Severity was coded to NCI CTCAE version 4.02. For maximum severity and relationship, patients were counted only once in the most severe or most related category. | Baseline to study completion (approximately 3 months) |
| Progression Free Survival (PFS) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC) | For Part B only. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (ie, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation. | Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01 | Area under the DKN-01 serum concentration-time profile curve during the dosing interval (AUC0-tau) after the first and fourth infusion for both Parts A and B. Cycle 1 Day 1 included once per week (QW) dosing groups and every two weeks (Q2W) dosing groups. | Cycle 1 Day 1 (first dose, all groups) |
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Inclusion Criteria:
Part A: Patients with histological or cytological confirmed multiple myeloma or advanced solid tumors. For multiple myeloma, must have symptomatic myeloma as defined by the International Myeloma Working Group inclusive of measurable serum and/or urine monoclonal protein (M-protein) or for those without elevations they must have measurable increased concentrations of free light chains
Part B: Patients with previously treated, histologically confirmed advanced NSCLC with progressive disease requiring therapy
Parts A and B:
Refractory or intolerant to all standard/approved therapy(ies)
Patients with solid tumors must have one or more metastatic tumors measurable on computed tomography (CT) scan using Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Radiation for symptomatic lesions outside the central nervous system (CNS) must have been completed at least 2 week prior to study enrollment
Treated brain metastases will be allowed, if they are asymptomatic. Patients must be off corticosteroids for at least 2 week prior to study entry
Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1
Life expectancy of at least 3 months
Ambulatory patients greater than or equal to (≥) 30 years of age
Females with child bearing potential must have a negative serum pregnancy test within 7 days of study entry
Acceptable liver function, renal function, hematologic status
Urinalysis - No clinically significant abnormalities
Acceptable coagulation status:
Prothrombin Time/Partial Thromboplastin Time (PT/PTT) ≤ 1.2 x upper limit of normal (ULN) (unless receiving anticoagulation therapy - eligibility based upon INR)
International Normalization Ratio (INR) ≤ 1.6 (unless receiving anticoagulant therapy)
For men and women of child-producing potential, the use of effective contraceptive methods during the study and for women 18 months following the last dose of study drug
Available for the study duration and willing to follow procedures
Serum calcium:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Cyndi Sirard, MD | Heatlhcare Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scottsdale Healthcare | Scottsdale | Arizona | 85258 | United States | ||
| New York Oncology Hematology, P.C. |
Part A enrolled patients with histologically or cytologically confirmed multiple myeloma or advanced solid tumors. A dose escalation procedure was followed. Part B enrolled patients with non-small cell lung cancer. Following screening (up to 28 days prior to first treatment) if entry criterion was met, patients were eligible for enrollment.
Eight sites in the United States participated in the study and 7 of them enrolled patients. The Date of First Enrollment was 16 Jan 2012, and the Date of Last Completed was 06 Dec 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | 75 Milligram (mg) DKN-01 Part A (QW) | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| FG001 | 150 mg DKN-01 Part A (QW) | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. |
| FG002 | 300 mg DKN-01 Part A (QW) | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| FG003 | 600 mg DKN-01 Part A (Q2W) | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| FG004 | 300 mg DKN-01 Part B (Q2W) | Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 75 Milligram (mg) DKN-01 Part A | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Summary of Total Adverse Events (AE) | Total Adverse Events (AE), total treatment emergent adverse events (TEAE), total Serious Adverse Events (SAE), and total dose-limiting toxicity (DLT) for both Parts A and B. | Safety analyses were based on the full analysis set (FAS), which was defined as all patients who received at least one dose of study treatment during Part A or Part B of the study. | Posted | Number | Events | Baseline to study completion (approximately 3 months) |
|
Entirety of the study. 1 year, 3 months.
Safety analyses were based on the full analysis set (FAS), which was defined as all patients who received at least one dose of study treatment during Part A or Part B of the study. Assessments up to 30 days after the date of last dose of study medication (for serious adverse events and unresolved study drug-related AEs) were included.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 75 Milligram (mg) DKN-01 Part A | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CARDIO-RESPIRATORY ARREST | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NAUSEA | Gastrointestinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Cynthia Sirard, MD | Healthcare Pharmaceuticals, Inc | 617-714-0357 | CSirard@hcven.com |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
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|
| 600 mg DKN-01 Part A | Experimental | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
|
| 300 mg DKN-01 Part B | Experimental | Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle. |
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| Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01 | Area under the DKN-01 serum concentration-time profile curve during the dosing interval (AUC0-tau) after the first and fourth infusion for both Parts A and B. Cycle 1 day 22 included only QW dosing groups. | Cycle 1 Day 22 (Fourth Dose for QW) |
| Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01 | Peak DKN-01 serum concentration (Cmax) after the first and fourth infusion on Cycle 1 Weeks 1 and 4, for both Parts A and B. Cycle 1 Day 1 included once per week (QW) dosing groups and every two weeks (Q2W) dosing groups. | Cycle 1 Day 1 (first dose, all groups) |
| Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01 | Peak DKN-01 serum concentration (Cmax) after the fourth infusion on Cycle 1 Weeks 1 and 4, for both Parts A and B. Cycle 1 day 22 included only QW dosing groups. | Cycle 1 Day 22 (Fourth dose for QW groups) |
| Progression Free Survival (PFS) in Patients Who Are Refractory or Intolerant to Standard/Approved Therapies | For both Parts A and B. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (i.e, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation. | Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause |
| Overall Survival (OS) in Patients With Relapsed or Refractory NSCLC | For Part B only. OS was defined as the time from the date of signed informed consent to the date of death from any cause. For patients who were still alive as of the data cut-off date, OS time was censored on the date of the patient's last contact (last contact for patients in post-discontinuation was the last date of contact in long-term follow-up eCRF). | Time from the date of signed informed consent to the date of death from any cause |
| Objective Response Rate (ORR) in Oncologic Patients Who Are Refractory or Intolerant to Standard/Approved Therapies | For both Parts A and B. Objective response rate is defined as the number of patients with overall best response of complete response (CR) or partial response (PR) | Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter |
| Objective Response Rate (ORR) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC) | FAS : For both Parts A and B. Objective response rate is defined as the number of patients with overall best response of complete response (CR) or partial response (PR) | Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter |
| Albany |
| New York |
| 12206 |
| United States |
| Greenville Hospital System University Medical Center | Greenville | South Carolina | 29605 | United States |
| Texas Oncology - Baylor, Charles A. Sammonds Cancer Center | Dallas | Texas | 75246 | United States |
| Texas Oncology - Tyler | Tyler | Texas | 75702 | United States |
| Virginia Oncology Associated | Norfolk | Virginia | 23502 | United States |
| Virginia Commonwealth University - Massey Cancer Center | Richmond | Virginia | 23298 | United States |
| Northwest Cancer Specialists, P.C. | Vancouver | Washington | 98684 | United States |
| BG001 | 150 mg DKN-01 Part A | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. |
| BG002 | 300 mg DKN-01 Part A | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| BG003 | 600 mg DKN-01 Part A | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| BG004 | 300 mg DKN-01 Part B | Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle. |
| BG005 | Total | Total of all reporting groups |
| years |
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG001 | 150 mg DKN-01 Part A (QW) | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. |
| OG002 | 300 mg DKN-01 Part A (QW) | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| OG003 | 600 mg DKN-01 Part A (Q2W) | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| OG004 | 300 mg DKN-01 Part B (Q2W) | Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle. |
| OG005 | Total | Total across all treatment groups |
|
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| Primary | Summary of Patients With Adverse Events (AE) | Number of patients who had Adverse Events (AE) including treatment related treatment emergent adverse events (TEAE), Common Toxicity Criteria for Adverse Effects (CTCAE), and Serious Adverse Events (SAE) for both Parts A and B. Severity was coded to NCI CTCAE version 4.02. For maximum severity and relationship, patients were counted only once in the most severe or most related category. | Safety analyses were based on the full analysis set (FAS), which was defined as all patients who received at least one dose of study treatment during Part A or Part B of the study. | Posted | Number | Patients | Baseline to study completion (approximately 3 months) |
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| Secondary | Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01 | Area under the DKN-01 serum concentration-time profile curve during the dosing interval (AUC0-tau) after the first and fourth infusion for both Parts A and B. Cycle 1 Day 1 included once per week (QW) dosing groups and every two weeks (Q2W) dosing groups. | All patients who received at least one dose of study treatment during Part A or Part B of the study. | Posted | Mean | Standard Deviation | hr*ng/mL | Cycle 1 Day 1 (first dose, all groups) |
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| Secondary | Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01 | Area under the DKN-01 serum concentration-time profile curve during the dosing interval (AUC0-tau) after the first and fourth infusion for both Parts A and B. Cycle 1 day 22 included only QW dosing groups. | All patients who received at least one dose of study treatment during Part A study. | Posted | Mean | Standard Deviation | hr*ng/mL | Cycle 1 Day 22 (Fourth Dose for QW) |
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| Secondary | Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01 | Peak DKN-01 serum concentration (Cmax) after the first and fourth infusion on Cycle 1 Weeks 1 and 4, for both Parts A and B. Cycle 1 Day 1 included once per week (QW) dosing groups and every two weeks (Q2W) dosing groups. | All patients who received at least one dose of study treatment during Part A or Part B of the study. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 Day 1 (first dose, all groups) |
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| Secondary | Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01 | Peak DKN-01 serum concentration (Cmax) after the fourth infusion on Cycle 1 Weeks 1 and 4, for both Parts A and B. Cycle 1 day 22 included only QW dosing groups. | All patients who received at least one dose of study treatment during Part A of the study. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 Day 22 (Fourth dose for QW groups) |
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| Secondary | Progression Free Survival (PFS) in Patients Who Are Refractory or Intolerant to Standard/Approved Therapies | For both Parts A and B. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (i.e, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation. | All patients who received at least one dose of study treatment during Part A or Part B of the study. | Posted | Median | 95% Confidence Interval | Months | Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause |
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| Secondary | Overall Survival (OS) in Patients With Relapsed or Refractory NSCLC | For Part B only. OS was defined as the time from the date of signed informed consent to the date of death from any cause. For patients who were still alive as of the data cut-off date, OS time was censored on the date of the patient's last contact (last contact for patients in post-discontinuation was the last date of contact in long-term follow-up eCRF). | For patients who are still alive as of the data cut-off date, OS time will be censored on the date of the patient's last contact (last contact for patients in post-discontinuation = last Date of Contact in Long Term Follow-up eCRF). | Posted | Median | 95% Confidence Interval | Months | Time from the date of signed informed consent to the date of death from any cause |
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| Secondary | Objective Response Rate (ORR) in Oncologic Patients Who Are Refractory or Intolerant to Standard/Approved Therapies | For both Parts A and B. Objective response rate is defined as the number of patients with overall best response of complete response (CR) or partial response (PR) | All patients with NSCLC who received at least one dose of study treatment during Part A or Part B of the study. One Patients from the 300 mg QW treatment group, and two patients from 300 mg Q2W treatment group did not have assessments performed after Baseline. | Posted | Number | 95% Confidence Interval | Participants | Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter |
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| Secondary | Objective Response Rate (ORR) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC) | FAS : For both Parts A and B. Objective response rate is defined as the number of patients with overall best response of complete response (CR) or partial response (PR) | FAS : NSCLC - All patients with NSCLC who received at least one dose of study treatment during Part A or Part B of the study. Two patients in treatment group 300 mg Q2W did not have assessments performed after Baseline. | Posted | Number | 95% Confidence Interval | participants | Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter |
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| Primary | Progression Free Survival (PFS) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC) | For Part B only. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (ie, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation. | Patients with advanced NSCLC receiving the study drug at 300 mg every 2 weeks in Part B | Posted | Median | 95% Confidence Interval | months | Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause |
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| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | 150 mg DKN-01 Part A | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. | 2 | 3 | 3 | 3 |
| EG002 | 300 mg DKN-01 Part A | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. | 1 | 4 | 4 | 4 |
| EG003 | 600 mg DKN-01 Part A | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. | 0 | 3 | 3 | 3 |
| EG004 | 300 mg DKN-01 Part B | Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle. | 6 | 19 | 16 | 19 |
| ASCITES | Gastrointestinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| VOMITING | Gastrointestinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| ATRIAL FIBRILLATION | Cardiac disorders | MedDRA (14.1) | Non-systematic Assessment |
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| PAIN MANAGEMENT | Surgical and medical procedures | MedDRA (14.1) | Non-systematic Assessment |
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| PLEURAL EFFUSION | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| PNEUMONIA | Infections and infestations | MedDRA (14.1) | Non-systematic Assessment |
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| PULMONARY EMBOLISM | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| SUPERIOR VENA CAVA SYNDROME | Vascular disorders | MedDRA (14.1) | Non-systematic Assessment |
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| PERICARDIAL EFFUSION | Cardiac disorders | MedDRA (14.1) | Non-systematic Assessment |
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| FATIGUE | General disorders | MedDRA (14.1) | Non-systematic Assessment |
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| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA (14.1) | Non-systematic Assessment |
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| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| VOMITTING | Gastrointestinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| CONSTIPATION | Gastrointestinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| ASTHENIA | General disorders | MedDRA (14.1) | Non-systematic Assessment |
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| DYSPHAGIA | Gastrointestinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| HYPOKALAEMIA | Metabolism and nutrition disorders | MedDRA (14.1) | Non-systematic Assessment |
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| PNEUMONIA | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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| PRODUCTIVE COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Non-systematic Assessment |
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Publication of the results shall not be made before the publication by Sponsor. If there is no multi-site publication within 18 months after the Study completion/termination at all sites, the Site shall have the right to publish its results. Prior to submitting to public release the Sponsor has 60 days from receipt to review and comment. The Site shall, upon Sponsor's request, further delay publication/presentation for up to 120 days to allow Sponsor to protect its interests.
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| At Least One TEAE |
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| At Least One SAE |
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| Retracted SAE |
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| SAE related to study drug |
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| TEAE of Maximum CTCAE - Grade 1 Mild |
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| TEAE of Maximum CTCAE - Grade 2 Moderate |
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| TEAE of Maximum CTCAE - Grade 3 Severe |
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| TEAE of Maximum CTCAE - Grade 4 Life Threatening |
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| TEAE of Maximum CTCAE - Grade 5 Death |
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| TEAE Grade ≥ 3 assessed as study drug related |
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| TEAE of Maximum Relationship - Related |
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| TEAE of Maximum Relationship - Not Related |
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| At Least One TEAE Leading to Drug Withdrawal |
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| At Least One TEAE Leading to Study Discontinuation |
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| At Least One TEAE with Outcome of Death |
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