Colorectal Cancer, Gastric Cancer, Non-small Cell Lung Cancer, Pancreatic Cancer, Renal Cell Carcinoma, Triple Negative Breast Cancer, Urothelial Cancer
Conditions
Brief summary
The purpose of the trial is to evaluate the safety of GEN1029 (HexaBody®-DR5/DR5) in a mixed population of patients with specified solid tumors
Detailed description
The trial is an open-label, multi-center first-in-human trial of GEN1029 (HexaBody®-DR5/DR5). The trial consists of two parts a dose escalation part (phase 1, first-in-human (FIH) and an expansion part (phase 2a). The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined.
Interventions
BIOLOGICALGEN1029 (HexaBody®-DR5/DR5)
GEN1029 will be administered intravenously. The dose levels will be determined by the starting dose and the escalation steps taken in the trial.
Sponsors
Genmab
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(main): * Patients with advanced and/or metastatic cancer who have no available standard therapy or who are not candidates for available standard therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1029 may be beneficial. * Patient must be ≥ 18 years of age * Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 * Have an acceptable hematological status * Have an acceptable renal function * Have an acceptable liver function * Have an Eastern Cooperative Oncology Group performance status of 0 or 1 * Body weight ≥ 40kg * Patients both females and males, of childbearing or reproductive potential must agree to use adequate contraception from screening visit until six months after last infusion of GEN1029
Exclusion criteria
(main): * Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 8 weeks prior to first GEN1029 administration * Have clinically significant cardiac disease * Have uncontrolled hypertension as defined in the protocol * Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke * History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of Investigational Medicinal Product (IMP) * Have received a cumulative dose of corticosteroid ≥ 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first GEN1029 administration * History of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial * Radiotherapy within 14 days prior to first GEN1029 administration * Any prior therapy with a compound targeting DR4 or DR5 * History of chronic liver disease or evidence of hepatic cirrhosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | From Day 1 to 28 days after the first dose of study drug | DLT criteria in the dose escalation phase of this trial are defined as hematologic toxicity including Grade (G) 4 neutropenia/thrombocytopenia for minimal duration of 7 days, G3/4 febrile neutropenia, \>=G3 thrombocytopenia with bleeding, or G4 anemia; and non-hematologic toxicity including G4 infusion-related reactions (IRR) or anaphylaxis, G3 IRR did not resolve to =\<G1 within 24 hours, \>=G3 diarrhea/vomiting (did not respond to optimal treatment within 2 days), G3 nausea (did not respond to optimal treatment within 7days), or Hy's law or protocol-specified toxicities related to liver function test results or amylase and/or lipase elevations; or any \>=G3 possibly related non-hematological AE, which occurred during first 2 cycles (as specified in protocol). |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Day 1 through Day 565 (corresponding to maximum observed duration) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is 'medically important'\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening during the treatment period including the safety follow-up period. |
| Number of Participants With >= Grade 3 Laboratory Results | Day 1 through Day 565 (corresponding to maximum observed duration) | Number of participants with laboratory measurements of Grade \>= 3 by NCI-CTCAE v4.03 are reported. The NCI-CTCAE is a descriptive terminology is used for AE reporting. The NCI-CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death. In case a participant reported multiple severity grades for an AE, only the maximum grade was used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 | The CL of Hx-DR5-01 and Hx-DR5-05 are reported. |
| Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 | The Vss of Hx-DR5-01 and Hx-DR5-05 are reported. |
| Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 | The t1/2 of Hx-DR5-01 and Hx-DR5-05 are reported. |
| Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 | The Tmax of Hx-DR5-01 and Hx-DR5-05 are reported. |
| Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 | The plasma concentration of Hx-DR5-01 and Hx-DR5-05 are reported. |
| Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029 | From Screening (Day -21 to -1) through Day 478 (corresponding to maximum observed duration) | From positive ADA samples titer values and neutralizing antibody scores (positive or negative) were determined and reported. A participant was considered positive if negative at baseline (screening) and had at least one positive post-baseline result, or positive at baseline and had at least one positive post-baseline result with a titer higher than baseline. Number of participants with ADA positive to GEN1029 are reported. |
| Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 | The Cmax of Hx-DR5-01 and Hx-DR5-05 are reported. |
| Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | From Day 1 through 8.8 months (corresponding to maximum observed duration) | The radiological evaluation was based on RECIST v1.1 using CT scan/PET-CT scan. The OR was defined as complete response (CR) or partial response (PR) per RECIST v1.1. The CR was defined as disappearance of all target and non-target lesions and reduction in short axis to \<10 mm of any pathological and non-pathological lymph nodes. The PR was defined as \>=30% decrease in sum of diameters of target lesions (compared to baseline), no unequivocal progression of existing non-target lesions, and no new lesion. |
| Progression-Free Survival (PFS) According to RECIST 1.1 | From Day 1 through 8.8 months (corresponding to maximum observed duration) | The PFS was defined as the number of days from the date of first study drug administration to first progressive disease (PD) or death from any cause. The PD was defined as at least 20% (and \>= 5 mm) increase in the sum of the longest diameter (LD) of target lesions, compared to the smallest sum of the target LDs recorded while in trial or the appearance of 1 or more new lesions; unequivocal progression of existing non-target lesions; and/or new lesion. The radiological evaluation based on RECIST v1.1 was assessed using CT scan/PET scan. The PFS was estimated using Kaplan-Meier method. |
| Overall Survival (OS) According to RECIST 1.1 | From Day 1 through 8.8 months (corresponding to maximum observed duration) | Overall survival was defined as the number of days from date of first study drug administration to death due to any cause. If a subject was not known to have died, then OS was censored, and the censoring date was the latest date the subject was known to be alive (on or before the cut-off date). The OS was estimated using Kaplan-Meier method. |
| Duration of Response (DoR) According to RECIST 1.1 | From Day 1 through 8.8 months (corresponding to maximum observed duration) | The radiological evaluation based on RECIST v1.1 was assessed using CT scan/PET-CT scan. The DoR was defined as duration from the first documentation of confirmed OR (CR or PR) to date of first progressive disease (PD) or death. |
| Time to Response (TTR) According to RECIST 1.1 | From Day 1 through 8.8 months (corresponding to maximum observed duration) | TTR is defined as the number of days from first dose of study drug to the first documented confirmed CR or PR, which must be subsequently confirmed. |
| Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage | From Baseline (Day 1) through 8.8 months (corresponding to maximum observed duration) | Anti-tumor activity measured by tumor shrinkage was evaluated on based on of sum of the diameter(s) of all target lesions from the computerized tomography (CT) scan/positron emission tomography (PET)-CT scan. Largest tumor shrinkage is reported. |
| Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 | The AUC(0-inf) of Hx-DR5-01 and Hx-DR5-05 are reported. |
| Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 | The AUC(0-Clast) of Hx-DR5-01 and Hx-DR5-05 are reported. |
Countries
Spain, United Kingdom, United States
Participant flow
Pre-assignment details
The sponsor decided to halt the development of GEN1029 due to a narrow therapeutic window after the dose-escalation part, hence the expansion part of the trial was not performed. Therefore, results are reported here only for the dose-escalation part.
Participants by arm
| Arm | Count |
|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) Participants received 0.1 mg/kg of GEN1029 every 2 weeks (Q2W) until the end of treatment. | 10 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) Participants received 0.2 mg/kg of GEN1029 Q2W until the end of treatment. | 7 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) Participants received 0.3 mg/kg of GEN1029 Q2W until the end of treatment. | 4 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) Participants received 1.0 mg/kg of GEN1029 Q2W until the end of treatment. | 11 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) Participants received 2.0 mg/kg of GEN1029 Q2W until the end of treatment. | 7 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) Participants received 3.0 mg/kg of GEN1029 Q2W until the end of treatment. | 7 |
| Priming Regimen (GEN1029 0.1 mg/kg) Participants received a priming dose of 0.1 mg/kg of GEN1029 on Cycle 1 Day 1. After 14 days and thereafter once every 14 days, participants received full dose of 0.3 mg/kg until the end of treatment. | 1 |
| Intensified Regimen (GEN1029 1.0 mg/kg) Participants received 1.0 mg/kg of GEN1029 once a week (Q1W) for the first 8 weeks then Q2W until the end of treatment. | 1 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 3 | 1 | 5 | 4 | 1 | 0 | 1 |
| Overall Study | Investigator decision | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | New anti-cancer treatment | 5 | 1 | 2 | 3 | 0 | 0 | 0 | 0 |
| Overall Study | Subject non-compliance | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Unspecified reason | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 1 | 2 | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Biweekly Regimen (GEN1029 0.2 mg/kg) | Biweekly Regimen (GEN1029 0.1 mg/kg) | Biweekly Regimen (GEN1029 0.3 mg/kg) | Biweekly Regimen (GEN1029 1.0 mg/kg) | Biweekly Regimen (GEN1029 2.0 mg/kg) | Biweekly Regimen (GEN1029 3.0 mg/kg) | Priming Regimen (GEN1029 0.1 mg/kg) | Intensified Regimen (GEN1029 1.0 mg/kg) |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 3 Participants | 7 Participants | 2 Participants | 7 Participants | 3 Participants | 4 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 6 Participants | 10 Participants | 3 Participants | 10 Participants | 6 Participants | 6 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 5 Participants | 8 Participants | 3 Participants | 11 Participants | 7 Participants | 7 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 27 Participants | 1 Participants | 6 Participants | 2 Participants | 8 Participants | 5 Participants | 4 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 21 Participants | 6 Participants | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 10 | 3 / 7 | 1 / 4 | 5 / 11 | 4 / 7 | 1 / 7 | 0 / 1 | 1 / 1 |
| other Total, other adverse events | 8 / 10 | 7 / 7 | 4 / 4 | 11 / 11 | 7 / 7 | 7 / 7 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 3 / 10 | 3 / 7 | 2 / 4 | 9 / 11 | 6 / 7 | 4 / 7 | 0 / 1 | 1 / 1 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT criteria in the dose escalation phase of this trial are defined as hematologic toxicity including Grade (G) 4 neutropenia/thrombocytopenia for minimal duration of 7 days, G3/4 febrile neutropenia, \>=G3 thrombocytopenia with bleeding, or G4 anemia; and non-hematologic toxicity including G4 infusion-related reactions (IRR) or anaphylaxis, G3 IRR did not resolve to =\<G1 within 24 hours, \>=G3 diarrhea/vomiting (did not respond to optimal treatment within 2 days), G3 nausea (did not respond to optimal treatment within 7days), or Hy's law or protocol-specified toxicities related to liver function test results or amylase and/or lipase elevations; or any \>=G3 possibly related non-hematological AE, which occurred during first 2 cycles (as specified in protocol).
Time frame: From Day 1 to 28 days after the first dose of study drug
Population: The Dose-Determining Set (DDS) consists of all participants from the Safety Set (received at least one dose of GEN1029 and analyzed according to the actual trial treatment received) who either received between 80% and 125% of the planned dose and completed the DLT observation period (Days 1-28), or experienced a DLT during Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 3 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 3 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
Primary
Number of Participants With >= Grade 3 Laboratory Results
Number of participants with laboratory measurements of Grade \>= 3 by NCI-CTCAE v4.03 are reported. The NCI-CTCAE is a descriptive terminology is used for AE reporting. The NCI-CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death. In case a participant reported multiple severity grades for an AE, only the maximum grade was used.
Time frame: Day 1 through Day 565 (corresponding to maximum observed duration)
Population: The Safety Set consists of all participants who received at least one dose of GEN1029 and analyzed according to the actual trial treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Activated partial thromboplastin time prolonged | 0 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lymphocytes decreased | 2 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alkaline phosphatase increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alanine aminotransferase increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lipase increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Sodium decreased | 1 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Prothrombin international normalized ratio - increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Hemoglobin decreased | 0 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Glucose increased | 2 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Gamma-glutamyl transferase increased | 2 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Creatinine increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Urate increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Magnesium increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Calcium decreased | 0 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Bilirubin increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Asparate aminotransferase increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Amylase increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alanine aminotransferase increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Sodium decreased | 1 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Urate increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Activated partial thromboplastin time prolonged | 1 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Prothrombin international normalized ratio - increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alkaline phosphatase increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Amylase increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Asparate aminotransferase increased | 2 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Bilirubin increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Calcium decreased | 1 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Creatinine increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Gamma-glutamyl transferase increased | 2 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Glucose increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Hemoglobin decreased | 1 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lipase increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lymphocytes decreased | 3 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Magnesium increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Magnesium increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Gamma-glutamyl transferase increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Urate increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Prothrombin international normalized ratio - increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Calcium decreased | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alanine aminotransferase increased | 2 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Creatinine increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lipase increased | 3 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lymphocytes decreased | 1 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Asparate aminotransferase increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Amylase increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Hemoglobin decreased | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Sodium decreased | 1 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alkaline phosphatase increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Glucose increased | 1 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Bilirubin increased | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Activated partial thromboplastin time prolonged | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Prothrombin international normalized ratio - increased | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Amylase increased | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lymphocytes decreased | 2 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Asparate aminotransferase increased | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Urate increased | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Bilirubin increased | 1 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Calcium decreased | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Creatinine increased | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Gamma-glutamyl transferase increased | 2 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Sodium decreased | 1 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Glucose increased | 3 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Magnesium increased | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Hemoglobin decreased | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lipase increased | 1 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Activated partial thromboplastin time prolonged | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alanine aminotransferase increased | 3 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alkaline phosphatase increased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Urate increased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Glucose increased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lipase increased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Gamma-glutamyl transferase increased | 3 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Activated partial thromboplastin time prolonged | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alkaline phosphatase increased | 1 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Bilirubin increased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Asparate aminotransferase increased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Amylase increased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Hemoglobin decreased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Calcium decreased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Prothrombin international normalized ratio - increased | 2 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Creatinine increased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lymphocytes decreased | 2 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Sodium decreased | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alanine aminotransferase increased | 1 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Magnesium increased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Bilirubin increased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Gamma-glutamyl transferase increased | 1 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Glucose increased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Asparate aminotransferase increased | 2 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alanine aminotransferase increased | 2 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Hemoglobin decreased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Prothrombin international normalized ratio - increased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Magnesium increased | 1 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lipase increased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Activated partial thromboplastin time prolonged | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Urate increased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Calcium decreased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Sodium decreased | 1 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Alkaline phosphatase increased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Creatinine increased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Lymphocytes decreased | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With >= Grade 3 Laboratory Results | Amylase increased | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is 'medically important'\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening during the treatment period including the safety follow-up period.
Time frame: Day 1 through Day 565 (corresponding to maximum observed duration)
Population: The Safety Set consists of all participants who received at least one dose of GEN1029 and analyzed according to the actual trial treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 3 Participants |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 8 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 3 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 7 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 2 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 4 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 11 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 9 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 7 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 6 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 4 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 7 Participants |
Secondary
Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05
The AUC(0-inf) of Hx-DR5-01 and Hx-DR5-05 are reported.
Time frame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
Population: PK analysis set included all participants who were exposed to at least 1 dose of GEN1029 and who had at least 1 post-dose PK measurement. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 1 Day 1 | 39.44 µg*h/mL | Geometric Coefficient of Variation 50.2 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 2 Day 1 | 46.37 µg*h/mL | Geometric Coefficient of Variation 61.5 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 3 Day 1 | 37.43 µg*h/mL | Geometric Coefficient of Variation 74 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 1 Day 1 | 32.97 µg*h/mL | Geometric Coefficient of Variation 55.4 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 2 Day 1 | 39.31 µg*h/mL | Geometric Coefficient of Variation 65.9 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 3 Day 1 | 25.87 µg*h/mL | Geometric Coefficient of Variation 57.3 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 2 Day 1 | 105.32 µg*h/mL | Geometric Coefficient of Variation 55.8 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 1 Day 1 | 71.21 µg*h/mL | Geometric Coefficient of Variation 66.9 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 3 Day 1 | 51.36 µg*h/mL | Geometric Coefficient of Variation 161.6 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 1 Day 1 | 91.20 µg*h/mL | Geometric Coefficient of Variation 66 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 3 Day 1 | 53.24 µg*h/mL | Geometric Coefficient of Variation 133.3 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 2 Day 1 | 93.11 µg*h/mL | Geometric Coefficient of Variation 66.6 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 3 Day 1 | 67.23 µg*h/mL | Geometric Coefficient of Variation 200.5 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 2 Day 1 | 44.76 µg*h/mL | Geometric Coefficient of Variation 184.4 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 1 Day 1 | 83.37 µg*h/mL | Geometric Coefficient of Variation 51.7 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 3 Day 1 | 41.41 µg*h/mL | Geometric Coefficient of Variation 84.9 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 1 Day 1 | 85.80 µg*h/mL | Geometric Coefficient of Variation 56.7 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 2 Day 1 | 35.24 µg*h/mL | Geometric Coefficient of Variation 30.5 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 1 Day 1 | 508.76 µg*h/mL | Geometric Coefficient of Variation 33 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 2 Day 1 | 530.48 µg*h/mL | Geometric Coefficient of Variation 24.8 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 3 Day 1 | 422.32 µg*h/mL | Geometric Coefficient of Variation 26.8 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 3 Day 1 | 231.49 µg*h/mL | Geometric Coefficient of Variation 53.2 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 2 Day 1 | 414.90 µg*h/mL | Geometric Coefficient of Variation 24.1 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 1 Day 1 | 523.66 µg*h/mL | Geometric Coefficient of Variation 47.5 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 1 Day 1 | 1298.0 µg*h/mL | Geometric Coefficient of Variation 22.7 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 2 Day 1 | 609.90 µg*h/mL | Geometric Coefficient of Variation 55.2 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 2 Day 1 | 1071.5 µg*h/mL | Geometric Coefficient of Variation 30.7 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 3 Day 1 | 1097.8 µg*h/mL | Geometric Coefficient of Variation 36.6 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 1 Day 1 | 1052.1 µg*h/mL | Geometric Coefficient of Variation 24.7 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 3 Day 1 | 412.87 µg*h/mL | Geometric Coefficient of Variation 64.1 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 1 Day 1 | 1270.0 µg*h/mL | Geometric Coefficient of Variation 60.1 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 3 Day 1 | 2653.5 µg*h/mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 2 Day 1 | 2273.6 µg*h/mL | Geometric Coefficient of Variation 9 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-05 Cycle 3 Day 1 | 2398.5 µg*h/mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 2 Day 1 | 2488.5 µg*h/mL | Geometric Coefficient of Variation 10.7 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-inf) Hx-DR5-01 Cycle 1 Day 1 | 1497.7 µg*h/mL | Geometric Coefficient of Variation 58.7 |
Secondary
Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05
The AUC(0-Clast) of Hx-DR5-01 and Hx-DR5-05 are reported.
Time frame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
Population: PK analysis set included all participants who were exposed to at least 1 dose of GEN1029 and who had at least 1 post-dose PK measurement. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 1 Day 1 | 24.36 µg*h/mL | Geometric Coefficient of Variation 73.2 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 2 Day 1 | 17.34 µg*h/mL | Geometric Coefficient of Variation 141.3 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 2 Day 1 | 24.85 µg*h/mL | Geometric Coefficient of Variation 119.4 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 1 Day 1 | 25.41 µg*h/mL | Geometric Coefficient of Variation 120.7 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 3 Day 1 | 22.34 µg*h/mL | Geometric Coefficient of Variation 85.9 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 3 Day 1 | 20.12 µg*h/mL | Geometric Coefficient of Variation 168.7 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 3 Day 1 | 16.95 µg*h/mL | Geometric Coefficient of Variation 539.4 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 2 Day 1 | 60.75 µg*h/mL | Geometric Coefficient of Variation 76 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 2 Day 1 | 70.33 µg*h/mL | Geometric Coefficient of Variation 66.4 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 1 Day 1 | 72.25 µg*h/mL | Geometric Coefficient of Variation 70.6 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 3 Day 1 | 35.31 µg*h/mL | Geometric Coefficient of Variation 151.4 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 1 Day 1 | 53.76 µg*h/mL | Geometric Coefficient of Variation 77 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 3 Day 1 | 43.56 µg*h/mL | Geometric Coefficient of Variation 405.4 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 3 Day 1 | 6.85 µg*h/mL | Geometric Coefficient of Variation 995 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 1 Day 1 | 60.78 µg*h/mL | Geometric Coefficient of Variation 35.8 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 2 Day 1 | 29.17 µg*h/mL | Geometric Coefficient of Variation 165.1 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 2 Day 1 | 21.85 µg*h/mL | Geometric Coefficient of Variation 36 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 1 Day 1 | 53.80 µg*h/mL | Geometric Coefficient of Variation 50.8 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 1 Day 1 | 460.37 µg*h/mL | Geometric Coefficient of Variation 43.5 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 2 Day 1 | 258.67 µg*h/mL | Geometric Coefficient of Variation 60.5 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 1 Day 1 | 432.18 µg*h/mL | Geometric Coefficient of Variation 24.5 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 2 Day 1 | 308.74 µg*h/mL | Geometric Coefficient of Variation 66.8 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 3 Day 1 | 385.54 µg*h/mL | Geometric Coefficient of Variation 23.7 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 3 Day 1 | 158.98 µg*h/mL | Geometric Coefficient of Variation 76.4 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 2 Day 1 | 395.50 µg*h/mL | Geometric Coefficient of Variation 62.3 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 3 Day 1 | 52.16 µg*h/mL | Geometric Coefficient of Variation 22162.5 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 2 Day 1 | 582.57 µg*h/mL | Geometric Coefficient of Variation 84.8 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 3 Day 1 | 986.38 µg*h/mL | Geometric Coefficient of Variation 30.1 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 1 Day 1 | 956.02 µg*h/mL | Geometric Coefficient of Variation 18.8 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 1 Day 1 | 1173.7 µg*h/mL | Geometric Coefficient of Variation 15.6 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 3 Day 1 | 2248.1 µg*h/mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 1 Day 1 | 1058.9 µg*h/mL | Geometric Coefficient of Variation 88.6 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 2 Day 1 | 2291.4 µg*h/mL | Geometric Coefficient of Variation 18.1 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-01 Cycle 3 Day 1 | 2444.7 µg*h/mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 1 Day 1 | 964.48 µg*h/mL | Geometric Coefficient of Variation 91.1 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05 | AUC(0-Clast) Hx-DR5-05 Cycle 2 Day 1 | 2176.0 µg*h/mL | Geometric Coefficient of Variation 11.7 |
Secondary
Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage
Anti-tumor activity measured by tumor shrinkage was evaluated on based on of sum of the diameter(s) of all target lesions from the computerized tomography (CT) scan/positron emission tomography (PET)-CT scan. Largest tumor shrinkage is reported.
Time frame: From Baseline (Day 1) through 8.8 months (corresponding to maximum observed duration)
Population: Full analysis set included all participants who received at least one dose of GEN1029 and were analyzed according to the actual treatment received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage | 12.0 millimeter | Standard Deviation 11.843 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage | 12.0 millimeter | Standard Deviation 17.616 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage | 13.75 millimeter | Standard Deviation 9.032 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage | 1.10 millimeter | Standard Deviation 9.049 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage | 9.0 millimeter | Standard Deviation 10.909 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage | 15.50 millimeter | Standard Deviation 18.574 |
Secondary
Duration of Response (DoR) According to RECIST 1.1
The radiological evaluation based on RECIST v1.1 was assessed using CT scan/PET-CT scan. The DoR was defined as duration from the first documentation of confirmed OR (CR or PR) to date of first progressive disease (PD) or death.
Time frame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
Population: Full analysis set included all participants who received at least one dose of GEN1029 and were analyzed according to the actual trial treatment received. Participants who achieved confirmed OR by the investigator assessment were evaluated for this outcome measure.
Secondary
Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05
The t1/2 of Hx-DR5-01 and Hx-DR5-05 are reported.
Time frame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
Population: PK analysis set included all participants who were exposed to at least 1 dose of GEN1029 and who had at least 1 post-dose PK measurement. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 1 Day 1 | 35.55 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 1 Day 1 | 41.69 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 2 Day 1 | 37.75 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 3 Day 1 | 25.30 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 3 Day 1 | 27.64 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 2 Day 1 | 32.46 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 2 Day 1 | 37.71 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 1 Day 1 | 34.50 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 3 Day 1 | 18.75 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 3 Day 1 | 19.93 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 1 Day 1 | 41.31 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 2 Day 1 | 39.57 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 1 Day 1 | 18.10 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 2 Day 1 | 24.47 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 3 Day 1 | 41.26 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 2 Day 1 | 25.43 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 1 Day 1 | 19.10 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 3 Day 1 | 20.16 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 1 Day 1 | 40.27 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 2 Day 1 | 49.64 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 3 Day 1 | 47.86 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 1 Day 1 | 36.33 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 2 Day 1 | 37.69 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 3 Day 1 | 33.90 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 2 Day 1 | 33.62 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 3 Day 1 | 22.83 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 1 Day 1 | 70.90 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 2 Day 1 | 26.68 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 1 Day 1 | 42.68 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 3 Day 1 | 44.51 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 1 Day 1 | 37.71 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 2 Day 1 | 65.85 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 2 Day 1 | 51.97 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 1 Day 1 | 42.45 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-05 Cycle 3 Day 1 | 70.9 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 | T1/2 Hx-DR5-01 Cycle 3 Day 1 | 77.00 h |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05
The Cmax of Hx-DR5-01 and Hx-DR5-05 are reported.
Time frame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
Population: Pharmacokinetic (PK) analysis set included all participants who were exposed to at least 1 dose of GEN1029 and who had at least 1 post-dose PK measurement. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 1 (Day 1) | 0.86 µg/mL | Geometric Coefficient of Variation 36.8 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 2 (Day 1) | 0.79 µg/mL | Geometric Coefficient of Variation 42.9 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 3 (Day 1) | 0.89 µg/mL | Geometric Coefficient of Variation 16.6 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 1 (Day 1) | 0.87 µg/mL | Geometric Coefficient of Variation 45.2 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 2 (Day 1) | 0.79 µg/mL | Geometric Coefficient of Variation 25.9 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 3 (Day 1) | 0.87 µg/mL | Geometric Coefficient of Variation 26.6 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 2 (Day 1) | 2.11 µg/mL | Geometric Coefficient of Variation 18.3 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 1 (Day 1) | 1.81 µg/mL | Geometric Coefficient of Variation 35.7 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 3 (Day 1) | 1.28 µg/mL | Geometric Coefficient of Variation 93.8 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 1 (Day 1) | 1.90 µg/mL | Geometric Coefficient of Variation 38 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 3 (Day 1) | 1.82 µg/mL | Geometric Coefficient of Variation 53.9 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 2 (Day 1) | 2.00 µg/mL | Geometric Coefficient of Variation 18.3 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 3 (Day 1) | 1.62 µg/mL | Geometric Coefficient of Variation 108.2 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 2 (Day 1) | 1.11 µg/mL | Geometric Coefficient of Variation 76.2 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 1 (Day 1) | 2.82 µg/mL | Geometric Coefficient of Variation 31.8 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 3 (Day 1) | 0.89 µg/mL | Geometric Coefficient of Variation 146.4 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 1 (Day 1) | 2.81 µg/mL | Geometric Coefficient of Variation 28.9 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 2 (Day 1) | 1.12 µg/mL | Geometric Coefficient of Variation 59.9 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 1 (Day 1) | 9.72 µg/mL | Geometric Coefficient of Variation 17 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 2 (Day 1) | 8.36 µg/mL | Geometric Coefficient of Variation 22.7 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 3 (Day 1) | 7.20 µg/mL | Geometric Coefficient of Variation 11.2 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 3 (Day 1) | 6.77 µg/mL | Geometric Coefficient of Variation 20.6 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 2 (Day 1) | 7.75 µg/mL | Geometric Coefficient of Variation 25.8 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 1 (Day 1) | 9.79 µg/mL | Geometric Coefficient of Variation 20.9 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 1 (Day 1) | 21.31 µg/mL | Geometric Coefficient of Variation 24.6 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 2 (Day 1) | 20.37 µg/mL | Geometric Coefficient of Variation 14.3 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 2 (Day 1) | 13.13 µg/mL | Geometric Coefficient of Variation 156.3 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 3 (Day 1) | 20.35 µg/mL | Geometric Coefficient of Variation 24.7 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 1 (Day 1) | 20.90 µg/mL | Geometric Coefficient of Variation 21.9 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 3 (Day 1) | 5.27 µg/mL | Geometric Coefficient of Variation 577.8 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 1 (Day 1) | 29.44 µg/mL | Geometric Coefficient of Variation 27.9 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 3 (Day 1) | 28.80 µg/mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 2 (Day 1) | 30.52 µg/mL | Geometric Coefficient of Variation 5.8 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-05 Cycle 3 (Day 1) | 28.50 µg/mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 2 (Day 1) | 29.56 µg/mL | Geometric Coefficient of Variation 7.7 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 | Cmax Hx-DR5-01 Cycle 1 (Day 1) | 29.75 µg/mL | Geometric Coefficient of Variation 24.9 |
Secondary
Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029
From positive ADA samples titer values and neutralizing antibody scores (positive or negative) were determined and reported. A participant was considered positive if negative at baseline (screening) and had at least one positive post-baseline result, or positive at baseline and had at least one positive post-baseline result with a titer higher than baseline. Number of participants with ADA positive to GEN1029 are reported.
Time frame: From Screening (Day -21 to -1) through Day 478 (corresponding to maximum observed duration)
Population: The Immunogenicity Set consists of all participants who received at least one dose of GEN1029 and analyzed according to the actual treatment received and had at least one immunogenicity measurement taken.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029 | 5 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029 | 5 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029 | 4 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029 | 7 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029 | 5 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029 | 0 Participants |
Secondary
Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
The radiological evaluation was based on RECIST v1.1 using CT scan/PET-CT scan. The OR was defined as complete response (CR) or partial response (PR) per RECIST v1.1. The CR was defined as disappearance of all target and non-target lesions and reduction in short axis to \<10 mm of any pathological and non-pathological lymph nodes. The PR was defined as \>=30% decrease in sum of diameters of target lesions (compared to baseline), no unequivocal progression of existing non-target lesions, and no new lesion.
Time frame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
Population: Full analysis set included all participants who received at least one dose of GEN1029 and were analyzed according to the actual trial treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0 Participants |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0 Participants |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0 Participants |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0 Participants |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0 Participants |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0 Participants |
Secondary
Overall Survival (OS) According to RECIST 1.1
Overall survival was defined as the number of days from date of first study drug administration to death due to any cause. If a subject was not known to have died, then OS was censored, and the censoring date was the latest date the subject was known to be alive (on or before the cut-off date). The OS was estimated using Kaplan-Meier method.
Time frame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
Population: Full analysis set included all participants who received at least one dose of GEN1029 and were analyzed according to the actual trial treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Overall Survival (OS) According to RECIST 1.1 | 7.0 months |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Overall Survival (OS) According to RECIST 1.1 | 6.4 months |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Overall Survival (OS) According to RECIST 1.1 | 4.9 months |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Overall Survival (OS) According to RECIST 1.1 | 7.1 months |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Overall Survival (OS) According to RECIST 1.1 | 4.7 months |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Overall Survival (OS) According to RECIST 1.1 | 6.9 months |
Secondary
Plasma Concentration of Hx-DR5-01 and Hx-DR5-05
The plasma concentration of Hx-DR5-01 and Hx-DR5-05 are reported.
Time frame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
Population: PK analysis set included all participants who were exposed to at least 1 dose of GEN1029 and who had at least 1 post-dose PK measurement. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 3 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 2 Day 1 (predose) | 0.091 µg/mL | Geometric Coefficient of Variation 61 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 3 Day 1 (predose) | 0.101 µg/mL | Geometric Coefficient of Variation 94.6 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 2 Day 1 (predose) | 0.097 µg/mL | Geometric Coefficient of Variation 83.6 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 1 Day 1 (predose) | 0.085 µg/mL | Geometric Coefficient of Variation 38.5 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 1 Day 1 (predose) | 0.094 µg/mL | Geometric Coefficient of Variation 77.6 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 3 Day 1 (predose) | 0.119 µg/mL | Geometric Coefficient of Variation 138.5 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 3 Day 1 (predose) | 0.125 µg/mL | Geometric Coefficient of Variation 164.3 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 2 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 2 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 3 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 3 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 2 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 2 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 3 Day 1 (predose) | 0.094 µg/mL | Geometric Coefficient of Variation 58.8 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 2 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 3 Day 1 (predose) | 0.090 µg/mL | Geometric Coefficient of Variation 46.4 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 2 Day 1 (predose) | 0.084 µg/mL | Geometric Coefficient of Variation 34 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 3 Day 1 (predose) | 0.224 µg/mL | Geometric Coefficient of Variation 156.9 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 2 Day 1 (predose) | 0.230 µg/mL | Geometric Coefficient of Variation 77.8 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 3 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 2 Day 1 (predose) | 0.155 µg/mL | Geometric Coefficient of Variation 161.5 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 3 Day 1 (predose) | 0.568 µg/mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 2 Day 1 (predose) | 0.283 µg/mL | Geometric Coefficient of Variation 576.2 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-01 Cycle 3 Day 1 (predose) | 0.739 µg/mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 1 Day 1 (predose) | 0.075 µg/mL | Geometric Coefficient of Variation 0 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 | Plasma concentration Hx-DR5-05 Cycle 2 Day 1 (predose) | 0.240 µg/mL | Geometric Coefficient of Variation 372.5 |
Secondary
Progression-Free Survival (PFS) According to RECIST 1.1
The PFS was defined as the number of days from the date of first study drug administration to first progressive disease (PD) or death from any cause. The PD was defined as at least 20% (and \>= 5 mm) increase in the sum of the longest diameter (LD) of target lesions, compared to the smallest sum of the target LDs recorded while in trial or the appearance of 1 or more new lesions; unequivocal progression of existing non-target lesions; and/or new lesion. The radiological evaluation based on RECIST v1.1 was assessed using CT scan/PET scan. The PFS was estimated using Kaplan-Meier method.
Time frame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
Population: Full analysis set included all participants who received at least one dose of GEN1029 and were analyzed according to the actual trial treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Progression-Free Survival (PFS) According to RECIST 1.1 | 2.5 months |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Progression-Free Survival (PFS) According to RECIST 1.1 | 1.4 months |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Progression-Free Survival (PFS) According to RECIST 1.1 | 2.4 months |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Progression-Free Survival (PFS) According to RECIST 1.1 | 1.9 months |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Progression-Free Survival (PFS) According to RECIST 1.1 | 1.2 months |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Progression-Free Survival (PFS) According to RECIST 1.1 | 1.2 months |
Secondary
Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05
The Tmax of Hx-DR5-01 and Hx-DR5-05 are reported.
Time frame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
Population: PK analysis set included all participants who were exposed to at least 1 dose of GEN1029 and who had at least 1 post-dose PK measurement. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 1 Day 1 | 1.58 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 1 Day 1 | 1.75 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 2 Day 1 | 1.25 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 3 Day 1 | 1.08 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 2 Day 1 | 3.12 h |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 3 Day 1 | 1.08 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 2 Day 1 | 3.03 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 3 Day 1 | 1.48 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 1 Day 1 | 2.53 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 2 Day 1 | 2.19 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 1 Day 1 | 1.89 h |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 3 Day 1 | 1.83 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 1 Day 1 | 1.23 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 3 Day 1 | 1.18 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 2 Day 1 | 1.19 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 2 Day 1 | 1.30 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 3 Day 1 | 1.13 h |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 1 Day 1 | 2.36 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 3 Day 1 | 3.08 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 1 Day 1 | 2.00 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 2 Day 1 | 3.06 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 3 Day 1 | 1.42 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 1 Day 1 | 1.60 h |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 2 Day 1 | 2.26 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 3 Day 1 | 1.82 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 1 Day 1 | 1.35 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 2 Day 1 | 3.25 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 3 Day 1 | 1.13 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 2 Day 1 | 2.31 h |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 1 Day 1 | 1.30 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 2 Day 1 | 2.21 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 3 Day 1 | 3.1 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 1 Day 1 | 1.46 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 2 Day 1 | 1.11 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-05 Cycle 3 Day 1 | 3.1 h |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05 | Tmax Hx-DR5-01 Cycle 1 Day 1 | 1.46 h |
Secondary
Time to Response (TTR) According to RECIST 1.1
TTR is defined as the number of days from first dose of study drug to the first documented confirmed CR or PR, which must be subsequently confirmed.
Time frame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
Population: Full analysis set included all participants who received at least one dose of GEN1029 and were analyzed according to the actual trial treatment received. Participants who achieved confirmed OR by the investigator assessment were evaluated for this outcome measure.
Secondary
Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05
The CL of Hx-DR5-01 and Hx-DR5-05 are reported.
Time frame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
Population: PK analysis set included all participants who were exposed to at least 1 dose of GEN1029 and who had at least 1 post-dose PK measurement. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 1 Day 1 | 95.98 mL/h | Geometric Coefficient of Variation 53.8 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 2 Day 1 | 77.36 mL/h | Geometric Coefficient of Variation 70.2 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 2 Day 1 | 90.18 mL/h | Geometric Coefficient of Variation 69.4 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 1 Day 1 | 111.10 mL/h | Geometric Coefficient of Variation 62.5 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 3 Day 1 | 143.09 mL/h | Geometric Coefficient of Variation 50.5 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 3 Day 1 | 99.53 mL/h | Geometric Coefficient of Variation 57.1 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 1 Day 1 | 91.27 mL/h | Geometric Coefficient of Variation 51.4 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 2 Day 1 | 90.45 mL/h | Geometric Coefficient of Variation 67.1 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 2 Day 1 | 79.97 mL/h | Geometric Coefficient of Variation 51.8 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 3 Day 1 | 131.46 mL/h | Geometric Coefficient of Variation 76 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 3 Day 1 | 140.38 mL/h | Geometric Coefficient of Variation 77.3 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 1 Day 1 | 116.89 mL/h | Geometric Coefficient of Variation 51.3 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 2 Day 1 | 155.76 mL/h | Geometric Coefficient of Variation 72.6 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 1 Day 1 | 123.75 mL/h | Geometric Coefficient of Variation 69.9 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 3 Day 1 | 111.33 mL/h | Geometric Coefficient of Variation 12.9 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 1 Day 1 | 127.35 mL/h | Geometric Coefficient of Variation 69.3 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 2 Day 1 | 131.51 mL/h | Geometric Coefficient of Variation 240.7 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 3 Day 1 | 68.57 mL/h | Geometric Coefficient of Variation 42.2 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 3 Day 1 | 114.74 mL/h | Geometric Coefficient of Variation 59.8 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 2 Day 1 | 58.07 mL/h | Geometric Coefficient of Variation 31.8 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 1 Day 1 | 65.36 mL/h | Geometric Coefficient of Variation 56.5 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 2 Day 1 | 79.72 mL/h | Geometric Coefficient of Variation 28.8 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 1 Day 1 | 67.28 mL/h | Geometric Coefficient of Variation 37.4 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 3 Day 1 | 62.90 mL/h | Geometric Coefficient of Variation 42.5 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 3 Day 1 | 62.64 mL/h | Geometric Coefficient of Variation 26.1 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 3 Day 1 | 172.66 mL/h | Geometric Coefficient of Variation 78.9 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 1 Day 1 | 59.07 mL/h | Geometric Coefficient of Variation 31.4 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 2 Day 1 | 73.43 mL/h | Geometric Coefficient of Variation 28 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 1 Day 1 | 69.39 mL/h | Geometric Coefficient of Variation 29.2 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 2 Day 1 | 134.11 mL/h | Geometric Coefficient of Variation 51.9 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 3 Day 1 | 41.90 mL/h | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 2 Day 1 | 40.41 mL/h | Geometric Coefficient of Variation 3.7 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 3 Day 1 | 37.87 mL/h | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 2 Day 1 | 36.92 mL/h | Geometric Coefficient of Variation 2 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-01 Cycle 1 Day 1 | 69.50 mL/h | Geometric Coefficient of Variation 51 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 | CL Hx-DR5-05 Cycle 1 Day 1 | 81.96 mL/h | Geometric Coefficient of Variation 53.9 |
Secondary
Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05
The Vss of Hx-DR5-01 and Hx-DR5-05 are reported.
Time frame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
Population: PK analysis set included all participants who were exposed to at least 1 dose of GEN1029 and who had at least 1 post-dose PK measurement. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 1 Day 1 | 5366.8 mL | Geometric Coefficient of Variation 35 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 2 Day 1 | 4720.0 mL | Geometric Coefficient of Variation 34.9 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 3 Day 1 | 4622.7 mL | Geometric Coefficient of Variation 31.1 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 1 Day 1 | 4722.7 mL | Geometric Coefficient of Variation 55.6 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 2 Day 1 | 4899.3 mL | Geometric Coefficient of Variation 22.7 |
| Biweekly Regimen (GEN1029 0.1 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 3 Day 1 | 4812.5 mL | Geometric Coefficient of Variation 31.9 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 3 Day 1 | 5077.6 mL | Geometric Coefficient of Variation 24.1 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 1 Day 1 | 4788.6 mL | Geometric Coefficient of Variation 5 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 2 Day 1 | 4287.5 mL | Geometric Coefficient of Variation 10.5 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 1 Day 1 | 5242.9 mL | Geometric Coefficient of Variation 15.8 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 3 Day 1 | 4531.9 mL | Geometric Coefficient of Variation 6.7 |
| Biweekly Regimen (GEN1029 0.2 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 2 Day 1 | 4701.6 mL | Geometric Coefficient of Variation 15 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 1 Day 1 | 3666.8 mL | Geometric Coefficient of Variation 49.4 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 1 Day 1 | 3942.4 mL | Geometric Coefficient of Variation 63.6 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 2 Day 1 | 5283.0 mL | Geometric Coefficient of Variation 62 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 3 Day 1 | 3243.6 mL | Geometric Coefficient of Variation 14.3 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 2 Day 1 | 5177.9 mL | Geometric Coefficient of Variation 100.6 |
| Biweekly Regimen (GEN1029 0.3 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 3 Day 1 | 3577.1 mL | Geometric Coefficient of Variation 15.7 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 1 Day 1 | 3611.0 mL | Geometric Coefficient of Variation 26.5 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 2 Day 1 | 3998.1 mL | Geometric Coefficient of Variation 24 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 3 Day 1 | 4951.2 mL | Geometric Coefficient of Variation 42.4 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 1 Day 1 | 3834.6 mL | Geometric Coefficient of Variation 34.3 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 2 Day 1 | 4054.4 mL | Geometric Coefficient of Variation 16.4 |
| Biweekly Regimen (GEN1029 1.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 3 Day 1 | 4075.3 mL | Geometric Coefficient of Variation 26.2 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 2 Day 1 | 4334.9 mL | Geometric Coefficient of Variation 14.9 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 2 Day 1 | 4185.8 mL | Geometric Coefficient of Variation 17.3 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 3 Day 1 | 4227.1 mL | Geometric Coefficient of Variation 8.7 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 1 Day 1 | 4885.9 mL | Geometric Coefficient of Variation 18.8 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 1 Day 1 | 4291.6 mL | Geometric Coefficient of Variation 9.8 |
| Biweekly Regimen (GEN1029 2.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 3 Day 1 | 5130.8 mL | Geometric Coefficient of Variation 5.6 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 1 Day 1 | 4142.9 mL | Geometric Coefficient of Variation 21 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 3 Day 1 | 4118.5 mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 2 Day 1 | 3427.5 mL | Geometric Coefficient of Variation 25.1 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 2 Day 1 | 3187.8 mL | Geometric Coefficient of Variation 41 |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-05 Cycle 3 Day 1 | 4173.9 mL | — |
| Biweekly Regimen (GEN1029 3.0 mg/kg) | Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05 | Vss Hx-DR5-01 Cycle 1 Day 1 | 4127.3 mL | Geometric Coefficient of Variation 19.2 |