Advanced Malignancies, Metastatic Cancer
Conditions
Keywords
Solid tumor, adenocarcinoma of the endometrium, melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), glucocorticoid-induced tumor necrosis factor receptor (GITR)
Brief summary
This was an open-label, non-randomized Phase 1/2 safety study of INCAGN01876 in participants with advanced or metastatic solid tumors that was conducted in 2 parts. Part 1 is dose escalation and safety expansion which determines the optimal dose and maximum number of tolerated doses. Part 2 is dose expansion in which Part 1 recommended dose will be evaluated.
Interventions
DRUGINCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Sponsors
Incyte Biosciences International Sàrl
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent. * Part 1: Participants with advanced or metastatic solid tumors. * Part 2: Participants with advanced or metastatic adenocarcinoma of endometrium, melanoma, non-small cell lung cancer, and renal cell carcinoma. * Participants who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or participants who refuse standard treatment. * Presence of measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
Exclusion criteria
* Laboratory and medical history parameters not within the protocol-defined range. * Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug. * Has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting therapy. * Receipt of a live vaccine within 30 days of planned start of study therapy. * Active autoimmune disease. * Prior treatment with any tumor necrosis factor super family agonist. * Known active central nervous system metastases and/or carcinomatous meningitis. * Evidence of active, non-infectious pneumonitis or history of interstitial lung disease. * Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | From screening through 60 days after end of treatment, up to Month 15 | AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent AE is any AE either reported for first time or worsening of a pre-existing event after the first dose of study drug. Grade 1 AEs is defined as Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 AEs is defined as Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3 AEs is defined as the severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living and Grade 4 AEs as life-threatening consequences; urgent intervention indicated. Data is reported for Grade 3 and higher severity for this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Day 1 of Cycles 1 and 6 post-dose | — |
| Time to Maximum Concentration (Tmax) | Day 1 of Cycles 1 and 6 post-dose | — |
| Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Day 1 of Cycles 2, 3, 4, 6, and 7 post-dose | — |
| Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Day 1 of Cycles 1 and 6 post-dose | — |
| Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months | ORR is defined as the percentage of participants having complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease assessments. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Duration of Response (DOR) Per RECIST and mRECIST | Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months | DOR is defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Duration of Disease Control Per RECIST and mRECIST | Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months | Duration of disease control (CR, PR, and stable disease \[SD\]), as measured from first report of SD or better until disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. |
| Progression Free Survival (PFS) Per RECIST and mRECIST | Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months | PFS is defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. Progression is defined by RECIST and mRECIST as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute lesion increase of at least 5 mm or the appearance of new lesions. |
Countries
United States
Participant flow
Recruitment details
A total of 100 participants were enrolled at 7 study sites in the United States from 20 June 2016 to 16 December 2019.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: 0.03 mg/kg Q2W INCAGN01876 was administered at 0.03mg/kg Q2W as part of dose escalation. | 4 |
| Phase 1: 0.1 mg/kg Q2W INCAGN01876 was administered at 0.1mg/kg Q2W as part of dose escalation. | 4 |
| Phase 1: 0.3 mg/kg Q2W INCAGN01876 was administered at 0.3mg/kg Q2W as part of dose escalation. | 4 |
| Phase 1: 1.0 mg/kg Q2W INCAGN01876 was administered at 1.0mg/kg Q2W as part of dose escalation. | 3 |
| Phase 1: 3.0 mg/kg Q2W INCAGN01876 was administered at 3mg/kg Q2W as part of dose escalation. | 15 |
| Phase 1: 5.0 mg/kg Q2W INCAGN01876 was administered at 5mg/kg Q2W as part of dose escalation. | 18 |
| Phase 1: 10.0 mg/kg Q2W INCAGN01876 was administered at 10mg/kg Q2W as part of dose escalation. | 16 |
| Phase 1: 20.0 mg/kg Q2W INCAGN01876 was administered at 20mg/kg Q2W as part of dose escalation. | 4 |
| Phase 1: 400 mg Q4W INCAGN01876 was administered at 400mg Q4W as part of dose escalation. | 10 |
| Phase 2: 300 mg Q2W INCAGN01876 was administered at 300mg Q2W as part of dose escalation. | 22 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 3 | 1 | 1 | 4 | 5 | 3 | 1 | 1 | 5 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 1 | 1 |
| Overall Study | Reason not Specified | 0 | 0 | 0 | 1 | 1 | 2 | 3 | 1 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 | 1 | 7 | 6 | 9 | 1 | 6 | 10 |
Baseline characteristics
| Characteristic | Phase 1: 0.3 mg/kg Q2W | Phase 1: 0.03 mg/kg Q2W | Phase 1: 1.0 mg/kg Q2W | Phase 1: 3.0 mg/kg Q2W | Phase 1: 5.0 mg/kg Q2W | Phase 1: 10.0 mg/kg Q2W | Phase 1: 20.0 mg/kg Q2W | Phase 1: 400 mg Q4W | Phase 2: 300 mg Q2W | Total | Phase 1: 0.1 mg/kg Q2W |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 70.0 years STANDARD_DEVIATION 12.19 | 50.5 years STANDARD_DEVIATION 17.02 | 53.0 years STANDARD_DEVIATION 14.93 | 62.3 years STANDARD_DEVIATION 10.58 | 53.6 years STANDARD_DEVIATION 12.83 | 62.3 years STANDARD_DEVIATION 10.22 | 59.5 years STANDARD_DEVIATION 14.75 | 57.6 years STANDARD_DEVIATION 12.02 | 67.2 years STANDARD_DEVIATION 10.86 | 60.1 years STANDARD_DEVIATION 13.23 | 45.3 years STANDARD_DEVIATION 21.01 |
| ECOG Performance Status 0 | 3 Participants | 3 Participants | 2 Participants | 8 Participants | 10 Participants | 8 Participants | 1 Participants | 6 Participants | 12 Participants | 54 Participants | 1 Participants |
| ECOG Performance Status 1 | 1 Participants | 1 Participants | 1 Participants | 7 Participants | 8 Participants | 8 Participants | 3 Participants | 4 Participants | 10 Participants | 46 Participants | 3 Participants |
| ECOG Performance Status 2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Performance Status 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Performance Status 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Performance Status 5 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 4 Participants | 4 Participants | 3 Participants | 14 Participants | 16 Participants | 15 Participants | 4 Participants | 9 Participants | 19 Participants | 92 Participants | 4 Participants |
| Race/Ethnicity, Customized Ethnicity Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black/African-American | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 9 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Missing | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White/Caucasian | 2 Participants | 3 Participants | 2 Participants | 13 Participants | 15 Participants | 12 Participants | 4 Participants | 7 Participants | 21 Participants | 82 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants | 8 Participants | 7 Participants | 5 Participants | 1 Participants | 4 Participants | 10 Participants | 42 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 3 Participants | 7 Participants | 11 Participants | 11 Participants | 3 Participants | 6 Participants | 12 Participants | 58 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 | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 3 / 4 | 1 / 4 | 1 / 3 | 4 / 15 | 5 / 18 | 3 / 16 | 1 / 4 | 1 / 10 | 5 / 22 | 26 / 100 |
| other Total, other adverse events | 4 / 4 | 3 / 4 | 4 / 4 | 3 / 3 | 15 / 15 | 18 / 18 | 16 / 16 | 4 / 4 | 10 / 10 | 22 / 22 | 99 / 100 |
| serious Total, serious adverse events | 3 / 4 | 3 / 4 | 1 / 4 | 2 / 3 | 6 / 15 | 6 / 18 | 7 / 16 | 2 / 4 | 3 / 10 | 10 / 22 | 43 / 100 |
Outcome results
Primary
Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity
AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent AE is any AE either reported for first time or worsening of a pre-existing event after the first dose of study drug. Grade 1 AEs is defined as Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 AEs is defined as Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3 AEs is defined as the severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living and Grade 4 AEs as life-threatening consequences; urgent intervention indicated. Data is reported for Grade 3 and higher severity for this outcome measure.
Time frame: From screening through 60 days after end of treatment, up to Month 15
Population: The full analysis set (FAS) included all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: 0.03 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 4 Participants |
| Phase 1: 0.03 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 3 Participants |
| Phase 1: 0.1 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 4 Participants |
| Phase 1: 0.1 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 3 Participants |
| Phase 1: 0.3 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 4 Participants |
| Phase 1: 0.3 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 1 Participants |
| Phase 1: 1.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 3 Participants |
| Phase 1: 1.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 2 Participants |
| Phase 1: 3.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 8 Participants |
| Phase 1: 3.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 15 Participants |
| Phase 1: 5.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 11 Participants |
| Phase 1: 5.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 18 Participants |
| Phase 1: 10.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 9 Participants |
| Phase 1: 10.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 16 Participants |
| Phase 1: 20.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 4 Participants |
| Phase 1: 20.0 mg/kg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 3 Participants |
| Phase 1: 400 mg Q4W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 10 Participants |
| Phase 1: 400 mg Q4W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 3 Participants |
| Phase 2: 300 mg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | TEAEs | 22 Participants |
| Phase 2: 300 mg Q2W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | Grade 3 and Higher | 14 Participants |
Secondary
Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t)
Time frame: Day 1 of Cycles 1 and 6 post-dose
Population: The PK evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 0.03 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 70.7 microgram (μg)*hr/mL | Standard Deviation 29 |
| Phase 1: 0.1 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 302 microgram (μg)*hr/mL | Standard Deviation 115 |
| Phase 1: 0.3 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 6 | 1070 microgram (μg)*hr/mL | Standard Deviation 392 |
| Phase 1: 0.3 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 850 microgram (μg)*hr/mL | Standard Deviation 108 |
| Phase 1: 1.0 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 3130 microgram (μg)*hr/mL | Standard Deviation 254 |
| Phase 1: 1.0 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 6 | 7190 microgram (μg)*hr/mL | — |
| Phase 1: 3.0 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 6 | 16,200 microgram (μg)*hr/mL | — |
| Phase 1: 3.0 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 8880 microgram (μg)*hr/mL | Standard Deviation 2710 |
| Phase 1: 5.0 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 17,900 microgram (μg)*hr/mL | Standard Deviation 4970 |
| Phase 1: 5.0 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 6 | 33,700 microgram (μg)*hr/mL | — |
| Phase 1: 10.0 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 39,800 microgram (μg)*hr/mL | — |
| Phase 1: 10.0 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 6 | 79,000 microgram (μg)*hr/mL | — |
| Phase 1: 20.0 mg/kg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 67,500 microgram (μg)*hr/mL | Standard Deviation 7920 |
| Phase 1: 400 mg Q4W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 6 | 42,100 microgram (μg)*hr/mL | — |
| Phase 1: 400 mg Q4W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 25,400 microgram (μg)*hr/mL | — |
| Phase 2: 300 mg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 1 (After the First Dose) | 13,400 microgram (μg)*hr/mL | Standard Deviation 3520 |
| Phase 2: 300 mg Q2W | Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) | Cycle 6 | 22,000 microgram (μg)*hr/mL | Standard Deviation 6640 |
Secondary
Duration of Disease Control Per RECIST and mRECIST
Duration of disease control (CR, PR, and stable disease \[SD\]), as measured from first report of SD or better until disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
Population: The FAS included all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: 0.03 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | NA days |
| Phase 1: 0.03 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | NA days |
| Phase 1: 0.1 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | NA days |
| Phase 1: 0.1 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | NA days |
| Phase 1: 0.3 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | 169.0 days |
| Phase 1: 0.3 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | 169.0 days |
| Phase 1: 1.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | 91.0 days |
| Phase 1: 1.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | 91.0 days |
| Phase 1: 3.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | 58.5 days |
| Phase 1: 3.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | 58.5 days |
| Phase 1: 5.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | 58.0 days |
| Phase 1: 5.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | 58.0 days |
| Phase 1: 10.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | 62.0 days |
| Phase 1: 10.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | 62.0 days |
| Phase 1: 20.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | 61.0 days |
| Phase 1: 20.0 mg/kg Q2W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | 61.0 days |
| Phase 1: 400 mg Q4W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | 113.0 days |
| Phase 1: 400 mg Q4W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | 113.0 days |
| Phase 2: 300 mg Q2W | Duration of Disease Control Per RECIST and mRECIST | RECIST v1.1 | 213.0 days |
| Phase 2: 300 mg Q2W | Duration of Disease Control Per RECIST and mRECIST | mRECIST v1.1 | 213.0 days |
Secondary
Duration of Response (DOR) Per RECIST and mRECIST
DOR is defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
Population: The FAS included all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: 0.03 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | NA Days |
| Phase 1: 0.03 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | NA Days |
| Phase 1: 0.1 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | NA Days |
| Phase 1: 0.1 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | NA Days |
| Phase 1: 0.3 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | 169.0 Days |
| Phase 1: 0.3 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | 169.0 Days |
| Phase 1: 1.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | NA Days |
| Phase 1: 1.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | NA Days |
| Phase 1: 3.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | NA Days |
| Phase 1: 3.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | NA Days |
| Phase 1: 5.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | NA Days |
| Phase 1: 5.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | NA Days |
| Phase 1: 10.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | NA Days |
| Phase 1: 10.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | NA Days |
| Phase 1: 20.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | NA Days |
| Phase 1: 20.0 mg/kg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | NA Days |
| Phase 1: 400 mg Q4W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | NA Days |
| Phase 1: 400 mg Q4W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | NA Days |
| Phase 2: 300 mg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | RECIST v1.1 | NA Days |
| Phase 2: 300 mg Q2W | Duration of Response (DOR) Per RECIST and mRECIST | mRECIST v1.1 | NA Days |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 1 of Cycles 1 and 6 post-dose
Population: The pharmacokinetic (PK) evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 0.03 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 781 nanograms per millilitre (ng/mL) | Standard Deviation 135 |
| Phase 1: 0.1 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 2700 nanograms per millilitre (ng/mL) | Standard Deviation 779 |
| Phase 1: 0.3 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 6450 nanograms per millilitre (ng/mL) | Standard Deviation 1330 |
| Phase 1: 0.3 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 6 | 7420 nanograms per millilitre (ng/mL) | Standard Deviation 573 |
| Phase 1: 1.0 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 6 | 36,500 nanograms per millilitre (ng/mL) | — |
| Phase 1: 1.0 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 21,600 nanograms per millilitre (ng/mL) | Standard Deviation 321 |
| Phase 1: 3.0 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 6 | 107,000 nanograms per millilitre (ng/mL) | — |
| Phase 1: 3.0 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 66,000 nanograms per millilitre (ng/mL) | — |
| Phase 1: 5.0 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 6 | 176,000 nanograms per millilitre (ng/mL) | — |
| Phase 1: 5.0 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 128,000 nanograms per millilitre (ng/mL) | — |
| Phase 1: 10.0 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 6 | 409,000 nanograms per millilitre (ng/mL) | — |
| Phase 1: 10.0 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 283,000 nanograms per millilitre (ng/mL) | — |
| Phase 1: 20.0 mg/kg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 437,000 nanograms per millilitre (ng/mL) | — |
| Phase 1: 400 mg Q4W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 127,000 nanograms per millilitre (ng/mL) | — |
| Phase 1: 400 mg Q4W | Maximum Observed Plasma Concentration (Cmax) | Cycle 6 | 168,000 nanograms per millilitre (ng/mL) | — |
| Phase 2: 300 mg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 6 | 137,000 nanograms per millilitre (ng/mL) | — |
| Phase 2: 300 mg Q2W | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (After the First Dose) | 103,000 nanograms per millilitre (ng/mL) | — |
Secondary
Minimum Observed Plasma Concentration Over the Dose Interval (Cmin)
Time frame: Day 1 of Cycles 2, 3, 4, 6, and 7 post-dose
Population: The PK evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement). Data is presented for those cycles for which data is available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 0.03 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 6 | 0.0 ng/mL | Standard Deviation 0 |
| Phase 1: 0.03 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 0.0 ng/mL | Standard Deviation 0 |
| Phase 1: 0.03 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 0.0 ng/mL | Standard Deviation 0 |
| Phase 1: 0.03 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 42.1 ng/mL | Standard Deviation 48.8 |
| Phase 1: 0.1 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 7 | 0.0 ng/mL | Standard Deviation 0 |
| Phase 1: 0.1 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 29.1 ng/mL | Standard Deviation 50.5 |
| Phase 1: 0.1 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 460 ng/mL | Standard Deviation 131 |
| Phase 1: 0.1 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 6 | 0.0 ng/mL | Standard Deviation 0 |
| Phase 1: 0.1 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 206 ng/mL | Standard Deviation 187 |
| Phase 1: 0.3 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 7 | 939 ng/mL | Standard Deviation 1060 |
| Phase 1: 0.3 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 1390 ng/mL | Standard Deviation 1230 |
| Phase 1: 0.3 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 900 ng/mL | Standard Deviation 1050 |
| Phase 1: 0.3 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 6 | 1210 ng/mL | Standard Deviation 1260 |
| Phase 1: 0.3 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 1110 ng/mL | Standard Deviation 762 |
| Phase 1: 1.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 4910 ng/mL | Standard Deviation 1420 |
| Phase 1: 1.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 6 | 15,100 ng/mL | — |
| Phase 1: 1.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 10,300 ng/mL | — |
| Phase 1: 1.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 7 | 15,500 ng/mL | — |
| Phase 1: 1.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 8290 ng/mL | Standard Deviation 5530 |
| Phase 1: 3.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 6 | 34,900 ng/mL | — |
| Phase 1: 3.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 14,800 ng/mL | Standard Deviation 6160 |
| Phase 1: 3.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 7 | 41,100 ng/mL | — |
| Phase 1: 3.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 23,500 ng/mL | — |
| Phase 1: 3.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 25,700 ng/mL | — |
| Phase 1: 5.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 25,600 ng/mL | — |
| Phase 1: 5.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 46,700 ng/mL | — |
| Phase 1: 5.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 7 | 64,900 ng/mL | — |
| Phase 1: 5.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 6 | 71,800 ng/mL | — |
| Phase 1: 5.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 36,200 ng/mL | — |
| Phase 1: 10.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 6 | 133,000 ng/mL | — |
| Phase 1: 10.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 58,000 ng/mL | — |
| Phase 1: 10.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 89,200 ng/mL | — |
| Phase 1: 10.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 135,000 ng/mL | — |
| Phase 1: 10.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 7 | 124,000 ng/mL | — |
| Phase 1: 20.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 135,000 ng/mL | — |
| Phase 1: 20.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 117,000 ng/mL | — |
| Phase 1: 20.0 mg/kg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 95,400 ng/mL | — |
| Phase 1: 400 mg Q4W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 20,500 ng/mL | — |
| Phase 1: 400 mg Q4W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 6 | 21,300 ng/mL | — |
| Phase 1: 400 mg Q4W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 22,800 ng/mL | — |
| Phase 1: 400 mg Q4W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 13,000 ng/mL | — |
| Phase 1: 400 mg Q4W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 7 | 27,500 ng/mL | — |
| Phase 2: 300 mg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 4 | 31,600 ng/mL | — |
| Phase 2: 300 mg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 3 | 36,800 ng/mL | — |
| Phase 2: 300 mg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 7 | 63,400 ng/mL | — |
| Phase 2: 300 mg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 6 | 42,400 ng/mL | — |
| Phase 2: 300 mg Q2W | Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) | Cycle 2 | 22,800 ng/mL | Standard Deviation 5880 |
Secondary
Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST)
ORR is defined as the percentage of participants having complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease assessments. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
Population: The FAS included all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: 0.03 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 0.03 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 0.1 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 0.1 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 0.3 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 25.0 percentage of participants |
| Phase 1: 0.3 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 25.0 percentage of participants |
| Phase 1: 1.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 1.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 3.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 3.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 5.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 5.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 10.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 10.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 20.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 20.0 mg/kg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 400 mg Q4W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 0.0 percentage of participants |
| Phase 1: 400 mg Q4W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 0.0 percentage of participants |
| Phase 2: 300 mg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | RECIST v1.1 | 4.5 percentage of participants |
| Phase 2: 300 mg Q2W | Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | mRECIST v1.1 | 0.0 percentage of participants |
Secondary
Progression Free Survival (PFS) Per RECIST and mRECIST
PFS is defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. Progression is defined by RECIST and mRECIST as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute lesion increase of at least 5 mm or the appearance of new lesions.
Time frame: Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
Population: The FAS included all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: 0.03 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 1.64 months |
| Phase 1: 0.03 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 1.64 months |
| Phase 1: 0.1 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 1.84 months |
| Phase 1: 0.1 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 1.84 months |
| Phase 1: 0.3 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 6.70 months |
| Phase 1: 0.3 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 6.70 months |
| Phase 1: 1.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 1.48 months |
| Phase 1: 1.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 1.48 months |
| Phase 1: 3.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 1.87 months |
| Phase 1: 3.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 1.87 months |
| Phase 1: 5.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 1.87 months |
| Phase 1: 5.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 1.87 months |
| Phase 1: 10.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 1.84 months |
| Phase 1: 10.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 1.84 months |
| Phase 1: 20.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 2.78 months |
| Phase 1: 20.0 mg/kg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 2.78 months |
| Phase 1: 400 mg Q4W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 2.14 months |
| Phase 1: 400 mg Q4W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 2.14 months |
| Phase 2: 300 mg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under RECIST v1.1 | 1.87 months |
| Phase 2: 300 mg Q2W | Progression Free Survival (PFS) Per RECIST and mRECIST | PFS under mRECIST v1.1 | 1.87 months |
Secondary
Time to Maximum Concentration (Tmax)
Time frame: Day 1 of Cycles 1 and 6 post-dose
Population: The PK evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: 0.03 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |
| Phase 1: 0.1 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |
| Phase 1: 0.3 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |
| Phase 1: 0.3 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 6 | 0.1 hours (hr) |
| Phase 1: 1.0 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 6 | 4.0 hours (hr) |
| Phase 1: 1.0 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |
| Phase 1: 3.0 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 6 | 0.1 hours (hr) |
| Phase 1: 3.0 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |
| Phase 1: 5.0 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 6 | 0.1 hours (hr) |
| Phase 1: 5.0 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |
| Phase 1: 10.0 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 6 | 0.1 hours (hr) |
| Phase 1: 10.0 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |
| Phase 1: 20.0 mg/kg Q2W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |
| Phase 1: 400 mg Q4W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |
| Phase 1: 400 mg Q4W | Time to Maximum Concentration (Tmax) | Cycle 6 | 0.1 hours (hr) |
| Phase 2: 300 mg Q2W | Time to Maximum Concentration (Tmax) | Cycle 6 | 0.1 hours (hr) |
| Phase 2: 300 mg Q2W | Time to Maximum Concentration (Tmax) | Cycle 1 (After the First Dose) | 0.1 hours (hr) |