Melanoma
Conditions
Keywords
Melanoma, Neoplasm, CNTO 95, Dacarbazine, Intetumumab
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of the intetumumab, alone and in combination with dacarbazine, in patients with stage 4 melanoma.
Detailed description
This is a Phase 1/2, multi-center, randomized (the study medication is assigned by chance) study. This study will be conducted in 2 Phases (Phase 1 and Phase 2). Phase 1 of this study will be non-randomized, open-label (all people know the identity of the intervention) and dose-escalation phase. It includes screening period and treatment period, which consists of 2 parts (Part 1 and Part 2). In Part 1, participants will receive 1 of 3 single dose levels of intetumumab \[3 milligram per kilogram (mg/kg), 5 mg/kg or 10 mg/kg\]. Part 2 will include 2 dose cohorts: dacarbazine plus intetumumab (5 mg/kg) or dacarbazine plus intetumumab (10 mg/kg). Phase 2 of this study will be randomized, blinded (neither physician nor participant knows the intervention which the participant will receive) and controlled (an inactive substance and other medication is compared with a study medication to test whether the medication has a real effect in this clinical study). This phase of the study will include screening period, treatment period (8 cycles of treatment with every cycle once in 3 weeks) and follow-up period (24 weeks). During the treatment period, participants will be randomly assigned to 1 of 4 treatment groups, Group 1: dacarbazine plus placebo, Group 2: intetumumab (5 mg/kg), Group 3: intetumumab (10 mg/kg) and Group 4: dacarbazine plus intetumumab. Randomization will be further based on the site of metastases and Eastern Cooperative Oncology Group performance status at Baseline. Single-medication intetumumab treatment groups will be open-label, while the dacarbazine plus intetumumab or placebo groups will be blinded. The total duration of the Phase 2 of this study will be up to 52 weeks or up to 76 weeks in case of extended dosing (extended administrations \[up to 8 additional cycles\] of the same assigned treatment will be allowed for participants that are responding to therapy with stable disease or better). Participants will be assessed for incidence of dose limiting toxicities, pharmacokinetics and tumor responses. Participants' safety will be monitored throughout the study.
Interventions
DRUGIntetumumab
Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.
DRUGDacarbazine
Commercially available dacarbazine will be administered intravenously over a 60-minute period (+30 minutes/-30 minutes) and prior to the intetumumab/placebo infusion. In case participants are unable to tolerate dacarbazine even after 2 dose reductions, they will be given the option to continue on intetumumab alone.
DRUGPlacebo
Placebo will be administered intravenously over a period of 2 hours (+15 minutes/-15 minutes).
Sponsors
Janssen-Cilag Farmaceutica, S.R.L.
Centocor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed melanoma including ocular and mucosal * Documented AJCC (American Joint Committee on Cancer) Stage 3 unresectable or Stage 4 melanoma (Phase 1); AJCC Stage 4 melanoma (Phase 2) * Radiographically measurable disease or measurable skin lesions * Prior chemotherapy for metastatic melanoma will be allowed for Phase 1, while previously untreated for melanoma by chemotherapy will be allowed for Phase 2 * Agrees to protocol-defined use of effective contraception
Exclusion criteria
* History of receiving murine or human/murine recombination products of human αν integrins * Known human immunodeficiency virus (HIV) positivity and clinically important active infection * Presence of bone metastases or malignant effusions (non-measurable lesions) and central nervous system metastases * Prior radiation to target lesions * Concurrent immunotherapy, biotherapy, radiotherapy, chemotherapy, or investigational therapy and therapeutic use of anticoagulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) - Phase 2 | From the date of randomization to date of initial documented progressive disease or death, whichever occured first, as assessed upto 6 months after last dose of study medication | The PFS was defined as the time from the date of randomization to the date of initial documented progressive disease (PD), or the date of initial documented symptomatic deterioration, or the date of death, whichever occurred first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as a reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions. |
| Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 1) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The R is obtained by dividing AUC at two different time points. |
| Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1 | Up to 21 days post-first infusion from the last treated participant in Phase 1 | The DLT is defined as any Grade 3 or higher adverse event identified by the safety data monitoring committee as attributable to intetumumab except for hypersensitivity reactions, which are not considered DLTs unless there are 2 or more occurrences of greater than or equal to Grade 3 hypersensitivity reaction within a group. |
| Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The maximum observed analyte concentration in serum was reported. |
| Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. |
| Half-life of Intetumumab - Phase 1 (Part 1) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half. |
| Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 1) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 1) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication) | The FACT-MS subscale is used to evaluate health related quality of life. It consists of 16 items: 12 items related to physical well-being, 3 to emotional well-being and 1 to social well-being. Scores for all items will range from 0 to 4. Total score ranges from 0-64; higher score indicates a more positive quality of life. |
| Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication) | The BPI questionnaire is used to evaluate heath related quality of life. BPI allows participants to rate the severity of their pain on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). |
| Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The maximum observed analyte concentration in serum was reported. |
| Half-life of Intetumumab - Phase 1 (Part 2) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half. |
| Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 2) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 2) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. |
| Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 2) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The R is obtained by dividing AUC at two different time points. |
| Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 2) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. |
| Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2 | Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable) | The CR: complete disappearance of all measurable and non-measurable target lesions and PR: 50 percent (%) or more decrease in sum of the longest diameters of target lesion(s), with at least stable disease (SD) in all other evaluable disease in the absence of treatment failure. The best response achieved among all the evaluated time points was reported. |
| Percentage of Participants Who Achieved CR - Phase 2 | Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable) | The CR: complete disappearance of all measurable and non-measurable target lesions. The participants who achieved CR as the best response were reported. |
| Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2 | Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable) | The SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), taking as a reference the smallest sum longest diameter since the treatment started. The participants who achieved SD as the best response were reported. |
| Overall Survival (OS) - Phase 2 | Every 3 months until death, until lost to follow-up, until withdrawal of consent, or until the Sponsor ends the study, as assessed up to 6 months post-last dose of study medication | The OS is defined as the time from the date of randomization to the date of death due to any cause and was to be censored at the date that the subject is last known to be alive. |
| Duration of Response - Phase 2 | From the time of initial documented response (CR or PR) to the first documented sign of progression, assessed up to 6 months post-last dose of study medication | Time duration required to achieve a CR or PR. |
| Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2 | Baseline (within 7 days of first infusion of study medication), Day 1 of all 8 cycles, 3 weeks or 1 week post-last dose, 3 months and 6 months post-last dose of study medication | Eastern Cooperative Oncology (ECOG) performance status: Participants will be graded from 0 (Fully active, able to carry on all pre-disease activities without restriction) to 4 (Completely disabled, cannot carry on any self-care, totally confined to bed or chair). Worsening in ECOG score was defined as ≥ 1 point increase in ECOG score from baseline. |
| Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2 | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The maximum observed analyte concentration in serum was reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Versus Time Curve Between Zero to Infinite Time (AUCinf) of Intetumumab - Phase 1 (Part 1) | Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose | The AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2 | Within 28 days of first infusion of study medication, within 1 week of the end of Cycles 2, 4, 6, 8; 3 months and 6 months post-last dose of study medication | The CR: complete disappearance of all measurable and non-measurable target lesions and PR: 50% or more decrease in sum of the longest diameters of target lesion(s), with at least stable disease (SD) in all other evaluable disease in the absence of treatment failure. |
Countries
Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] Intetumumab was administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation was not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab was discontinued in Part 1 and participants were treated at the highest, documented safe dose level at which receptor saturation was observed. | 3 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] Intetumumab was administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs. If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation was not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab was discontinued in Part 1 and participants were treated at the highest, documented safe dose level at which receptor saturation was observed. | 3 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs. | 3 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] Intetumumab was administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with stable disease (SD) or better, they were considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine was administered at the dose of 1000 milligram per meter-square (mg/m\^2) intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion. | 3 |
| Dacarbazine + Intetumumab 10 mg/kg [Phase 1 (Part 2)] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine was administered at the dose of 1000 mg/m\^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion. | 3 |
| Dacarbazine + Placebo [Phase 2] Placebo was administered intravenously over a period of 2 hr (±15 minutes). Commercially available dacarbazine was administered at the dose of 1000 mg/m\^2 intravenously over a period of 60 minutes (± 30 minutes) prior to placebo infusion. In case participants were unable to tolerate dacarbazine even after 2 dose reductions, they were given the option to continue with 10 mg/kg intetumumab alone. | 31 |
| Intetumumab 5 mg/kg [Phase 2] Intetumumab was administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations. | 31 |
| Intetumumab 10 mg/kg [Phase 2] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations. | 33 |
| Dacarbazine + Intetumumab 10 mg/kg [Phase 2] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine was administered at the dose of 1000 mg/m\^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion. | 32 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 |
| Overall Study | Disease progression | 3 | 1 | 2 | 3 | 3 | 25 | 30 | 27 | 26 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Randomly assigned but not treated | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Dacarbazine + Intetumumab 10 mg/kg [Phase 1 (Part 2)] | Dacarbazine + Placebo [Phase 2] | Intetumumab 5 mg/kg [Phase 2] | Intetumumab 10 mg/kg [Phase 2] | Dacarbazine + Intetumumab 10 mg/kg [Phase 2] | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | 62.0 Years STANDARD_DEVIATION 10.82 | 46.7 Years STANDARD_DEVIATION 6.66 | 61.7 Years STANDARD_DEVIATION 11.59 | 52.7 Years STANDARD_DEVIATION 15.01 | 66.0 Years STANDARD_DEVIATION 18.73 | 63.5 Years STANDARD_DEVIATION 14.17 | 67.3 Years STANDARD_DEVIATION 11.44 | 61.5 Years STANDARD_DEVIATION 12.39 | 57.2 Years STANDARD_DEVIATION 11.45 | 61.8 Years STANDARD_DEVIATION 12.87 |
| Region of Enrollment Germany | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants | 12 Participants | 10 Participants | 13 Participants | 44 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 9 Participants | 4 Participants | 5 Participants | 24 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 16 Participants | 10 Participants | 19 Participants | 14 Participants | 74 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 13 Participants | 8 Participants | 7 Participants | 14 Participants | 47 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 18 Participants | 23 Participants | 26 Participants | 18 Participants | 95 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 | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 2 / 3 | 3 / 3 | 3 / 3 | 30 / 31 | 30 / 31 | 32 / 33 | 30 / 32 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 0 / 3 | 1 / 3 | 2 / 3 | 9 / 31 | 4 / 31 | 6 / 33 | 7 / 32 |
Outcome results
Primary
Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 1)
The R is obtained by dividing AUC at two different time points.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. Serum concentration data was insufficient to robustly estimate the accumulation ratio.
Primary
Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1)
The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1) | 257.55 mcg*day/mL | — |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1) | 503.71 mcg*day/mL | — |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1) | 1479.07 mcg*day/mL | Standard Deviation 149.851 |
Primary
Half-life of Intetumumab - Phase 1 (Part 1)
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Half-life of Intetumumab - Phase 1 (Part 1) | 2.03 Days | — |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Half-life of Intetumumab - Phase 1 (Part 1) | 2.13 Days | — |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Half-life of Intetumumab - Phase 1 (Part 1) | 5.33 Days | Standard Deviation 1.001 |
Primary
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1)
The maximum observed analyte concentration in serum was reported.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The Pharmacokinetics (PK)-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1) | 94.44 Microgram per milliliter (mcg/mL) | Standard Deviation 9.037 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1) | 199.45 Microgram per milliliter (mcg/mL) | Standard Deviation 64.093 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1) | 306.86 Microgram per milliliter (mcg/mL) | Standard Deviation 54.979 |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1
The DLT is defined as any Grade 3 or higher adverse event identified by the safety data monitoring committee as attributable to intetumumab except for hypersensitivity reactions, which are not considered DLTs unless there are 2 or more occurrences of greater than or equal to Grade 3 hypersensitivity reaction within a group.
Time frame: Up to 21 days post-first infusion from the last treated participant in Phase 1
Population: Safety population included all the participants who received at least 1 (partial or complete) dose of intetumumab/placebo or dacarbazine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1 | 0 Participants |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1 | 0 Participants |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1 | 0 Participants |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1 | 0 Participants |
| Dacarbazine + Intetumumab 10 mg/kg [Phase 1 (Part 2)] | Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1 | 0 Participants |
Primary
Progression-Free Survival (PFS) - Phase 2
The PFS was defined as the time from the date of randomization to the date of initial documented progressive disease (PD), or the date of initial documented symptomatic deterioration, or the date of death, whichever occurred first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as a reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions.
Time frame: From the date of randomization to date of initial documented progressive disease or death, whichever occured first, as assessed upto 6 months after last dose of study medication
Population: The Intent-to-treat (ITT) population included all the participants who were randomly assigned to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Progression-Free Survival (PFS) - Phase 2 | 54.0 Days |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Progression-Free Survival (PFS) - Phase 2 | 42.0 Days |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Progression-Free Survival (PFS) - Phase 2 | 42.0 Days |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Progression-Free Survival (PFS) - Phase 2 | 75.0 Days |
Primary
Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 1)
The CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 1) | 11.85 mL/day/kg | — |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 1) | 9.96 mL/day/kg | — |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 1) | 6.79 mL/day/kg | Standard Deviation 1.634 |
Primary
Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 1)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 1) | 34.69 mL/kg | — |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 1) | 30.63 mL/kg | — |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 1) | 50.80 mL/kg | Standard Deviation 4.981 |
Secondary
Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 2)
The R is obtained by dividing AUC at two different time points.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. Serum concentration data was insufficient to robustly estimate the accumulation ratio.
Secondary
Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 2)
The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 2) | 368.74 mcg*day/mL | Standard Deviation 36.056 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 2) | 963.17 mcg*day/mL | — |
Secondary
Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2
The BPI questionnaire is used to evaluate heath related quality of life. BPI allows participants to rate the severity of their pain on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).
Time frame: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
Population: The ITT population included all the participants who were randomly assigned to treatment. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Baseline (Cycle 1) (n=23, 23, 27, 25) | 1.3 Units on a scale | Standard Deviation 1.77 |
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at Cycle 2 (pre-dose) (n=20, 22, 22, 22) | 0.9 Units on a scale | Standard Deviation 1.92 |
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at Cycle 3 (pre-dose) (n = 19, 10, 6, 14) | 0.5 Units on a scale | Standard Deviation 2.41 |
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at final visit (n = 15, 20, 20, 16) | 1.4 Units on a scale | Standard Deviation 2.85 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at Cycle 2 (pre-dose) (n=20, 22, 22, 22) | 0.0 Units on a scale | Standard Deviation 1.96 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at Cycle 3 (pre-dose) (n = 19, 10, 6, 14) | 0.5 Units on a scale | Standard Deviation 1.27 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at final visit (n = 15, 20, 20, 16) | 0.8 Units on a scale | Standard Deviation 1.8 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Baseline (Cycle 1) (n=23, 23, 27, 25) | 2.0 Units on a scale | Standard Deviation 2.5 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at Cycle 3 (pre-dose) (n = 19, 10, 6, 14) | 0.0 Units on a scale | Standard Deviation 0.63 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at Cycle 2 (pre-dose) (n=20, 22, 22, 22) | 0.5 Units on a scale | Standard Deviation 2.09 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at final visit (n = 15, 20, 20, 16) | 1.0 Units on a scale | Standard Deviation 1.96 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Baseline (Cycle 1) (n=23, 23, 27, 25) | 0.9 Units on a scale | Standard Deviation 1.79 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at final visit (n = 15, 20, 20, 16) | 0.3 Units on a scale | Standard Deviation 3.48 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at Cycle 2 (pre-dose) (n=20, 22, 22, 22) | -0.3 Units on a scale | Standard Deviation 1.94 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Baseline (Cycle 1) (n=23, 23, 27, 25) | 2.2 Units on a scale | Standard Deviation 2.37 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2 | Change at Cycle 3 (pre-dose) (n = 19, 10, 6, 14) | -0.8 Units on a scale | Standard Deviation 2.19 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2
The FACT-MS subscale is used to evaluate health related quality of life. It consists of 16 items: 12 items related to physical well-being, 3 to emotional well-being and 1 to social well-being. Scores for all items will range from 0 to 4. Total score ranges from 0-64; higher score indicates a more positive quality of life.
Time frame: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
Population: The ITT population included all the participants who were randomly assigned to treatment. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at final visit (n = 15, 20, 20, 17) | -5.7 Units on a scale | Standard Deviation 8.79 |
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at Cycle 2 (pre-dose) (n=20, 24, 22, 23) | -2.2 Units on a scale | Standard Deviation 8.13 |
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Baseline (Cycle 1) (n=23, 24, 26, 26) | 53.8 Units on a scale | Standard Deviation 8.26 |
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at Cycle 3 (pre-dose) (n = 19, 11, 5, 14) | -2.6 Units on a scale | Standard Deviation 7.18 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at Cycle 2 (pre-dose) (n=20, 24, 22, 23) | -1.9 Units on a scale | Standard Deviation 5.21 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at Cycle 3 (pre-dose) (n = 19, 11, 5, 14) | -1.3 Units on a scale | Standard Deviation 5.9 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Baseline (Cycle 1) (n=23, 24, 26, 26) | 55.6 Units on a scale | Standard Deviation 5.29 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at final visit (n = 15, 20, 20, 17) | -5.5 Units on a scale | Standard Deviation 7.08 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Baseline (Cycle 1) (n=23, 24, 26, 26) | 55.3 Units on a scale | Standard Deviation 6.91 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at Cycle 2 (pre-dose) (n=20, 24, 22, 23) | -2.9 Units on a scale | Standard Deviation 5.24 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at Cycle 3 (pre-dose) (n = 19, 11, 5, 14) | 0.2 Units on a scale | Standard Deviation 0.84 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at final visit (n = 15, 20, 20, 17) | -2.2 Units on a scale | Standard Deviation 4.61 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at Cycle 2 (pre-dose) (n=20, 24, 22, 23) | -2.0 Units on a scale | Standard Deviation 4.96 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Baseline (Cycle 1) (n=23, 24, 26, 26) | 53.3 Units on a scale | Standard Deviation 8.22 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at final visit (n = 15, 20, 20, 17) | -3.2 Units on a scale | Standard Deviation 8.39 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2 | Change at Cycle 3 (pre-dose) (n = 19, 11, 5, 14) | -0.1 Units on a scale | Standard Deviation 5.96 |
Secondary
Duration of Response - Phase 2
Time duration required to achieve a CR or PR.
Time frame: From the time of initial documented response (CR or PR) to the first documented sign of progression, assessed up to 6 months post-last dose of study medication
Population: The response-evaluable population included all the participants who were evaluable for response. The results were reported as individual participant's listings, but not statistically summarized.
Secondary
Half-life of Intetumumab - Phase 1 (Part 2)
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Half-life of Intetumumab - Phase 1 (Part 2) | 2.41 Days | Standard Deviation 0.559 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Half-life of Intetumumab - Phase 1 (Part 2) | 2.36 Days | — |
Secondary
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2)
The maximum observed analyte concentration in serum was reported.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2) | 118.47 Microgram per milliliter (mcg/mL) | Standard Deviation 33.462 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2) | 220.87 Microgram per milliliter (mcg/mL) | Standard Deviation 122.662 |
Secondary
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2
The maximum observed analyte concentration in serum was reported.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2 | NA mcg/mL | — |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2 | 131.18 mcg/mL | Standard Deviation 61.122 |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2 | 240.81 mcg/mL | Standard Deviation 87.332 |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2 | 219.47 mcg/mL | Standard Deviation 118.267 |
Secondary
Overall Survival (OS) - Phase 2
The OS is defined as the time from the date of randomization to the date of death due to any cause and was to be censored at the date that the subject is last known to be alive.
Time frame: Every 3 months until death, until lost to follow-up, until withdrawal of consent, or until the Sponsor ends the study, as assessed up to 6 months post-last dose of study medication
Population: The ITT population included all the participants who were randomly assigned to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Overall Survival (OS) - Phase 2 | 233.0 Days |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Overall Survival (OS) - Phase 2 | 298.0 Days |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Overall Survival (OS) - Phase 2 | 426.0 Days |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Overall Survival (OS) - Phase 2 | 333.5 Days |
Secondary
Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2
The CR: complete disappearance of all measurable and non-measurable target lesions and PR: 50 percent (%) or more decrease in sum of the longest diameters of target lesion(s), with at least stable disease (SD) in all other evaluable disease in the absence of treatment failure. The best response achieved among all the evaluated time points was reported.
Time frame: Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable)
Population: The response-evaluable population included all the participants who were evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2 | 9.7 Percentage of Participants |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2 | 0 Percentage of Participants |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2 | 6.1 Percentage of Participants |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2 | 3.3 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved CR - Phase 2
The CR: complete disappearance of all measurable and non-measurable target lesions. The participants who achieved CR as the best response were reported.
Time frame: Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable)
Population: The response-evaluable population included all the participants who were evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved CR - Phase 2 | 0 Percentage of Participants |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved CR - Phase 2 | 0 Percentage of Participants |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved CR - Phase 2 | 0 Percentage of Participants |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Percentage of Participants Who Achieved CR - Phase 2 | 0 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2
The SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), taking as a reference the smallest sum longest diameter since the treatment started. The participants who achieved SD as the best response were reported.
Time frame: Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable)
Population: The response-evaluable population included all the participants who were evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2 | 32.3 Percentage of Participants |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2 | 25.8 Percentage of Participants |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2 | 24.2 Percentage of Participants |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2 | 53.3 Percentage of Participants |
Secondary
Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2
Eastern Cooperative Oncology (ECOG) performance status: Participants will be graded from 0 (Fully active, able to carry on all pre-disease activities without restriction) to 4 (Completely disabled, cannot carry on any self-care, totally confined to bed or chair). Worsening in ECOG score was defined as ≥ 1 point increase in ECOG score from baseline.
Time frame: Baseline (within 7 days of first infusion of study medication), Day 1 of all 8 cycles, 3 weeks or 1 week post-last dose, 3 months and 6 months post-last dose of study medication
Population: The ITT population included all the participants who were randomly assigned to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2 | 135.0 Days |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2 | 226.0 Days |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2 | 194.0 Days |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2 | 170.0 Days |
Secondary
Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 2)
The CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 2) | 13.44 mL/day/kg | Standard Deviation 1.537 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 2) | 10.34 mL/day/kg | — |
Secondary
Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 2)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 2) | 47.38 mL/kg | Standard Deviation 16.187 |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 2) | 35.18 mL/kg | — |
Other Pre-specified
Area Under the Concentration Versus Time Curve Between Zero to Infinite Time (AUCinf) of Intetumumab - Phase 1 (Part 1)
The AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Population: The PK-evaluable population included all the participants who had at least 1 PK sample and who received at least 1 (partial or complete) dose of intetumumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Area Under the Concentration Versus Time Curve Between Zero to Infinite Time (AUCinf) of Intetumumab - Phase 1 (Part 1) | 257.80 mcg*day/mL | — |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Area Under the Concentration Versus Time Curve Between Zero to Infinite Time (AUCinf) of Intetumumab - Phase 1 (Part 1) | 503.88 mcg*day/mL | — |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Area Under the Concentration Versus Time Curve Between Zero to Infinite Time (AUCinf) of Intetumumab - Phase 1 (Part 1) | 1591.54 mcg*day/mL | Standard Deviation 213.858 |
Other Pre-specified
Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2
The CR: complete disappearance of all measurable and non-measurable target lesions and PR: 50% or more decrease in sum of the longest diameters of target lesion(s), with at least stable disease (SD) in all other evaluable disease in the absence of treatment failure.
Time frame: Within 28 days of first infusion of study medication, within 1 week of the end of Cycles 2, 4, 6, 8; 3 months and 6 months post-last dose of study medication
Population: The response-evaluable population included all the participants who were evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2 | 41.9 Percentage of Participants |
| Intetumumab 5 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2 | 25.8 Percentage of Participants |
| Intetumumab 10 mg/kg [Phase 1 (Part 1)] | Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2 | 30.3 Percentage of Participants |
| Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] | Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2 | 56.7 Percentage of Participants |