Melanoma, Solid Tumor, CRAF Gene Amplification, RAF1 Gene Amplification, BRAF Gene Fusion, BRAF Fusion, CRAF Gene Fusion, CRAF Fusion, RAF1 Gene Fusion, RAF1 Fusion, Thyroid Cancer, Papillary, Spitzoid Melanoma, Pilocytic Astrocytoma, Pilocytic Astrocytoma, Adult, Non Small Cell Lung Cancer, Non-Small Cell Adenocarcinoma, Colorectal Cancer, Pancreatic Acinar Carcinoma, Spitzoid Malignant Melanoma, Bladder Cancer, Bladder Urothelial Carcinoma, MAP Kinase Family Gene Mutation, RAF Mutation
Conditions
Keywords
BRAF fusion, CRAF/RAF1 fusion, CRAF/RAF1 amplification
Brief summary
This is a Phase 2, multi-center, open-label to evaluate the efficacy and safety of tovorafenib (DAY101) in participants ≥12 years of age with recurrent or progressive melanoma or solid tumors with BRAF fusion or CRAF/RAF1 fusions or amplification.
Interventions
DRUGTovorafenib
Tovorafenib tablet for oral use.
Sponsors
Day One Biopharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent by participants ≥ 12 years of age either a Consent or an Assent Form will be provided to the patient based on their capacity, local regulations, and guidelines. * Participants must have a histologically confirmed diagnosis of melanoma or other solid tumor and a BRAF fusion, CRAF/RAF1 fusion, or CRAF/RAF1 amplifications obtained through a tumor or liquid biopsy as assessed by genomic sequencing, polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or another clinically accepted molecular diagnostic method recognized by local laboratory or regulatory agency. * Participants must have radiographically-recurrent or radiographically-progressive disease that is measurable using the appropriate tumor response criteria (e.g. RECIST version 1.1 or RANO). * Archival tumor tissue (preferably less than 3 years old) or fresh tumor tissue for correlative studies is required * If brain metastases are present, they must have been previously treated and be stable as assessed by radiographic imaging
Exclusion criteria
* Prior therapy of any RAS-, RAF-, MEK-, or ERK-directed inhibitor therapy * Known presence of concurrent activating mutation * Participants with current evidence or a history of central serous retinopathy (CSR), retinal vein occlusion (RVO)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) by the Investigator | Up to 23 months | ORR was defined as the percentage of participants with the best overall confirmed response of complete response (CR) or partial response (PR) according to the appropriate response assessment criteria including Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for the disease setting as assessed by the Investigator. CR or PR was confirmed at a subsequent scan (\>=4 weeks) if the criteria for each are met . The exact 95% confidence intervals (CIs) were calculated using Clopper-Pearson method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Baseline and up to 23 months | Blood samples were collected for the analysis of following hematology parameters: anemia, neutrophil count decreased and white blood cell decreased. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G2, G3, and G4 are presented. The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. |
| Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Baseline and up to 23 months | Blood samples were collected for the analysis of following chemistry parameters: creatine phosphokinase (CPK) increased, hypokalemia, hypoalbuminemia, hypercalcemia, hypocalcemia and hyponatremia. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G2, G3, and G4 are presented. The laboratory parameters were graded according to CTCAE version 5. |
| Duration of Response (DOR) in Participants With Best Overall Response | Up to 23 months | Duration of response was defined as the interval from the date of the first documentation of tumor response (CR or PR) that was subsequently confirmed by investigator assessment to the date of first occurrence of radiographic disease progression based on RECIST 1.1 or RANO criteria or death due to any cause, whichever occurs earlier. DOR was estimated using Kaplan-Meier method. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to 23 months | An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. An AE is considered to be treatment-emergent if it has a start date/time on or after the first administration of study drug until 30 days after the last dose of study drug and before the start of subsequent therapy, whichever comes earlier. The distribution of AEs was analyzed by the type, frequency and severity for TEAEs. |
| Duration of Overall Survival | Up to 23 months | Overall survival is defined as the interval from the date of the first dose until the recorded date of death due to any cause. Overall survival was estimated using Kaplan-Meier method. |
| Time to Response | Up to 23 months | Time to Response was defined in participants with best overall response of complete response or partial response as determined by Investigator. It is the interval from the date of the first dose to date of first documentation of tumor response that was subsequently confirmed by investigator assessment. |
| Duration of Progression Free Survival | Up to 23 months | Progression free survival was defined as the interval from the date of the first dose to the first occurrence of radiographic disease progression based on RECIST 1.1 or RANO criteria or death due to any cause, whichever occurs earlier. Progression free survival was estimated using Kaplan-Meier method. |
Countries
Australia, Belgium, Canada, France, South Korea, Spain, United States
Participant flow
Recruitment details
This study was conducted at 11 centers that enrolled participants in 6 countries.
Pre-assignment details
A total of 31 participants consented, of which 23 participants were enrolled into Melanoma and Tissue Agnostic cohorts. Remaining 8 participants were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Melanoma Cohort Adult participants (≥ 18 years) were administered Tovorafenib 600 mg orally (PO) once weekly (QW). | 8 |
| Tissue Agnostic Cohort Adult participants (≥ 18 years) were administered Tovorafenib 600 mg PO QW. | 15 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Tissue Agnostic Cohort | Total | Melanoma Cohort |
|---|---|---|---|
| Age, Continuous | 45.0 Years | 53.0 Years | 58.0 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 21 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 13 Participants | 3 Participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 4 Participants |
| Sex: Female, Male Male | 8 Participants | 12 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 8 | 6 / 15 |
| other Total, other adverse events | 8 / 8 | 15 / 15 |
| serious Total, serious adverse events | 2 / 8 | 8 / 15 |
Outcome results
Primary
Overall Response Rate (ORR) by the Investigator
ORR was defined as the percentage of participants with the best overall confirmed response of complete response (CR) or partial response (PR) according to the appropriate response assessment criteria including Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for the disease setting as assessed by the Investigator. CR or PR was confirmed at a subsequent scan (\>=4 weeks) if the criteria for each are met . The exact 95% confidence intervals (CIs) were calculated using Clopper-Pearson method.
Time frame: Up to 23 months
Population: Efficacy Analysis Set comprises of all participants who received at least one dose of study drug and have measurable disease as determined by the Investigator at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melanoma Cohort | Overall Response Rate (ORR) by the Investigator | 50.0 Percentage of participants |
| Tissue Agnostic Cohort | Overall Response Rate (ORR) by the Investigator | 40.0 Percentage of participants |
Secondary
Duration of Overall Survival
Overall survival is defined as the interval from the date of the first dose until the recorded date of death due to any cause. Overall survival was estimated using Kaplan-Meier method.
Time frame: Up to 23 months
Population: Efficacy Analysis Set comprises of all participants who received at least one dose of study drug and have measurable disease as determined by the Investigator at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Melanoma Cohort | Duration of Overall Survival | 18.9 Months |
| Tissue Agnostic Cohort | Duration of Overall Survival | NA Months |
Secondary
Duration of Progression Free Survival
Progression free survival was defined as the interval from the date of the first dose to the first occurrence of radiographic disease progression based on RECIST 1.1 or RANO criteria or death due to any cause, whichever occurs earlier. Progression free survival was estimated using Kaplan-Meier method.
Time frame: Up to 23 months
Population: Efficacy Analysis Set comprises of all participants who received at least one dose of study drug and have measurable disease as determined by the Investigator at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Melanoma Cohort | Duration of Progression Free Survival | 5.5 Months |
| Tissue Agnostic Cohort | Duration of Progression Free Survival | 5.5 Months |
Secondary
Duration of Response (DOR) in Participants With Best Overall Response
Duration of response was defined as the interval from the date of the first documentation of tumor response (CR or PR) that was subsequently confirmed by investigator assessment to the date of first occurrence of radiographic disease progression based on RECIST 1.1 or RANO criteria or death due to any cause, whichever occurs earlier. DOR was estimated using Kaplan-Meier method.
Time frame: Up to 23 months
Population: Participants in the Efficacy Analysis Set who have a confirmed response of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Melanoma Cohort | Duration of Response (DOR) in Participants With Best Overall Response | 5.6 Months |
| Tissue Agnostic Cohort | Duration of Response (DOR) in Participants With Best Overall Response | 9.2 Months |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. An AE is considered to be treatment-emergent if it has a start date/time on or after the first administration of study drug until 30 days after the last dose of study drug and before the start of subsequent therapy, whichever comes earlier. The distribution of AEs was analyzed by the type, frequency and severity for TEAEs.
Time frame: Up to 23 months
Population: Safety Analysis Set comprises of all patients enrolled in the study who receive at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 8 Participants |
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Related to Study Drug | 8 Participants |
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any serious TEAE | 2 Participants |
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious TEAEs Related to Study Drug | 0 Participants |
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs with Severity Grade 3 or Higher | 5 Participants |
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Related to Study Drug with Severity Grade 3 or Higher | 2 Participants |
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Leading to Death | 0 Participants |
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Related to Study Drug Leading to Death | 0 Participants |
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Leading to Study Drug Discontinuation | 1 Participants |
| Melanoma Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Related to Study Drug Leading to Study Drug Discontinuation | 1 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Related to Study Drug Leading to Death | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any serious TEAE | 8 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 15 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Related to Study Drug with Severity Grade 3 or Higher | 3 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Related to Study Drug | 13 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Related to Study Drug Leading to Study Drug Discontinuation | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Leading to Death | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious TEAEs Related to Study Drug | 1 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs Leading to Study Drug Discontinuation | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs with Severity Grade 3 or Higher | 8 Participants |
Secondary
Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline
Blood samples were collected for the analysis of following chemistry parameters: creatine phosphokinase (CPK) increased, hypokalemia, hypoalbuminemia, hypercalcemia, hypocalcemia and hyponatremia. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G2, G3, and G4 are presented. The laboratory parameters were graded according to CTCAE version 5.
Time frame: Baseline and up to 23 months
Population: Safety Analysis Set comprises of all patients enrolled in the study who receive at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | CPK increased, Increased to Grade 2 | 2 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | CPK increased, Increased to Grade 3 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | CPK increased, Increased to Grade 4 | 1 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypoalbuminemia, Increased to Grade 2 | 1 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypoalbuminemia, Increased to Grade 3 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypoalbuminemia, Increased to Grade 4 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypokalemia, Increased to Grade 2 | 1 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypokalemia, Increased to Grade 3 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypokalemia, Increased to Grade 4 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hyponatremia, Increased to Grade 2 | 1 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hyponatremia, Increased to Grade 3 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hyponatremia, Increased to Grade 4 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypercalcemia, Increased to Grade 2 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypercalcemia, Increased to Grade 3 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypercalcemia, Increased to Grade 4 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypocalcemia, Increased to Grade 2 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypocalcemia, Increased to Grade 3 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypocalcemia, Increased to Grade 4 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypercalcemia, Increased to Grade 3 | 1 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | CPK increased, Increased to Grade 2 | 4 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hyponatremia, Increased to Grade 2 | 1 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | CPK increased, Increased to Grade 3 | 1 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypocalcemia, Increased to Grade 4 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | CPK increased, Increased to Grade 4 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hyponatremia, Increased to Grade 3 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypoalbuminemia, Increased to Grade 2 | 2 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypercalcemia, Increased to Grade 4 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypoalbuminemia, Increased to Grade 3 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hyponatremia, Increased to Grade 4 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypoalbuminemia, Increased to Grade 4 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypocalcemia, Increased to Grade 3 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypokalemia, Increased to Grade 2 | 5 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypercalcemia, Increased to Grade 2 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypokalemia, Increased to Grade 3 | 1 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypocalcemia, Increased to Grade 2 | 1 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline | Hypokalemia, Increased to Grade 4 | 0 Participants |
Secondary
Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline
Blood samples were collected for the analysis of following hematology parameters: anemia, neutrophil count decreased and white blood cell decreased. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G2, G3, and G4 are presented. The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Time frame: Baseline and up to 23 months
Population: Safety Analysis Set comprises of all patients enrolled in the study who receive at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Melanoma Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Anemia, Increased to Grade 3 | 2 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Neutrophil count decreased, Increased to Grade 4 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Neutrophil count decreased, Increased to Grade 2 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | White blood cell decreased, Increased to Grade 2 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Anemia, Increased to Grade 4 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | White blood cell decreased, Increased to Grade 3 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Neutrophil count decreased, Increased to Grade 3 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | White blood cell decreased, Increased to Grade 4 | 0 Participants |
| Melanoma Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Anemia, Increased to Grade 2 | 3 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | White blood cell decreased, Increased to Grade 4 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Anemia, Increased to Grade 2 | 5 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Anemia, Increased to Grade 3 | 2 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Anemia, Increased to Grade 4 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Neutrophil count decreased, Increased to Grade 2 | 2 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Neutrophil count decreased, Increased to Grade 3 | 1 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | Neutrophil count decreased, Increased to Grade 4 | 0 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | White blood cell decreased, Increased to Grade 2 | 2 Participants |
| Tissue Agnostic Cohort | Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline | White blood cell decreased, Increased to Grade 3 | 0 Participants |
Secondary
Time to Response
Time to Response was defined in participants with best overall response of complete response or partial response as determined by Investigator. It is the interval from the date of the first dose to date of first documentation of tumor response that was subsequently confirmed by investigator assessment.
Time frame: Up to 23 months
Population: Participants in the Efficacy Analysis Set who have a confirmed response of CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Melanoma Cohort | Time to Response | 1.76 Months |
| Tissue Agnostic Cohort | Time to Response | 1.82 Months |