Triple-Negative Breast Cancer
Conditions
Brief summary
The goals of this clinical study are to learn about the safety, tolerability, dosing and effectiveness of magrolimab in combination with nab-paclitaxel or paclitaxel (cohort 1) or with sacituzumab govitecan-hziy (cohort 2) in participants with non-surgically removable locally advanced or metastatic triple-negative breast cancer. The primary objective of this study for the safety run-in cohorts of the study is to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of magrolimab in combination with nab-paclitaxel or paclitaxel (Safety Run-In Cohort 1), and sacituzumab govitecan (Safety Run-In Cohort 2) in metastatic triple-negative breast cancer (mTNBC). This study in the Phase 2 Cohort 1 also compares the efficacy of magrolimab in combination with nab-paclitaxel or paclitaxel versus nab-paclitaxel or paclitaxel alone, as determined by progression-free survival (PFS) by investigator assessment. This study in the Phase 2 Cohort 2 also evaluates the efficacy of magrolimab in combination with sacituzumab govitecan as determined by confirmed objective response rate (ORR) by investigator assessment.
Interventions
DRUGMagrolimab
Administered intravenously
DRUGNab-Paclitaxel
Administered intravenously
DRUGPaclitaxel
Administered intravenously
DRUGSacituzumab Govitecan-hziy
Administered intravenously
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion criteria: * Adequate performance status, hematologic, renal and liver function. * Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1 * Cohort 1: Individuals with previously untreated with systemic therapy for unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) that are considered programmed cell death ligand 1 (PD-L1) negative (as determined by an approved test according to local regulations). * Cohort 2: Individuals with unresectable, locally advanced or metastatic breast cancer with a diagnosis of TNBC who have received at least 1 and no more than 2 prior lines of systemic therapy in the unresectable, locally advanced or metastatic setting. Individuals must have been previously treated with a taxane in any setting. Individuals with tumors that are considered positive for PD-L1 expression (as determined by an approved test according to local regulations) must have received an immune checkpoint inhibitor for a prior-line of treatment for unresectable locally advanced/metastatic TNBC. Key
Exclusion criteria
* Positive serum pregnancy test or breastfeeding female. * Active central nervous system (CNS) disease. Individuals with asymptomatic and stable, treated CNS lesions (who have been off steroids, radiation and/or surgery and/or other CNS-directed therapy for at least 4 weeks) are allowed. * Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed RBC transfusions during the 4-week period prior to screening. Red blood cell transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criteria. * History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months. * Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha-targeting agents. * Known inherited or acquired bleeding disorders. * Cohort 1 only: Disease progression within 6 months following neoadjuvant/adjuvant therapy. * Cohort 2 only: * Individuals with active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease) and Individuals with a history of bowel obstruction or gastrointestinal perforation within 6 months of enrollment. * Individuals who previously received topoisomerase I inhibitors or antibody-drug conjugates containing a topoisomerase inhibitor. * High-dose systemic corticosteroids (≥ 20 mg of prednisone or its equivalent) are not allowed within 2 weeks of Cycle 1 Day 1. * Have not recovered (ie, ≥ Grade 2 is considered not recovered) from adverse events (AEs) due to a previously administered agent. * Note: Individuals with any grade of neuropathy, alopecia, hypo- or hyperthyroidism, or other endocrinopathies that are well controlled with hormone replacement are an exception to this criterion and will qualify for the study. * Note: if individuals received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs) | First dose date up to 28 days (Cohort 1) and up to 21 days (Cohort 2) | A DLT is defined as any: * Grade 3 or higher hematologic toxicity including: * Hemolytic anemia that is medically significant, requiring hospitalization or prolongation of existing hospitalization, disabling, or limiting self-care activities of daily life. * Event meeting Hy's Law criteria: * Treatment-emergent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation (at least 3 x ULN), AND * Treatment-emergent total bilirubin elevation (more than 2 x ULN), and absence of cholestasis (defined as alkaline phosphatase less than 2 x ULN), AND * No other good explanation for the injury (hepatitis A, B, C, or other viral hepatic injury, alcohol ingestion, congestive heart failure, worsening liver metastases). * Grade 3 or higher nonhematologic toxicity that has worsened in severity from pretreatment baseline during the DLT assessment period, and in the opinion of the investigator, the AE is at least possibly related to magrolimab. |
| Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | First dose date up to last dose date (up to 73 weeks) plus 30 days | TEAEs are defined as any events not present prior to the study treatment, or any events already present but worsening in either intensity or frequency following exposure to the study treatment. TEAEs were any AEs with an onset date on or after the date of the first dose of study treatment up to 30 days after the date of the last dose of study treatment, or the day before initiation of subsequent anticancer therapy, whichever comes first. An AE is any untoward medical occurrence in a clinical study patient administered a study drug that does not necessarily have a causal relationship with the treatment. |
| Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 | First dose date up to last dose date (up to 73 weeks) plus 30 days | Treatment-emergent laboratory abnormalities according to NCI CTCAE V5.0 are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days and prior to the day before initiation of subsequent anti-cancer therapy. Grade 1 mild, Grade 2 moderate, Grade 3 severe, Grade 4 life-threatening and Grade 5 death. Percentages were rounded off. |
| Phase 2 Cohort 1: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Up to 107 weeks | PFS was defined as the time from the date of randomization until the earliest date of documented disease progression (PD), as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (KM) estimates were used in outcome measure analysis. |
| Safety Run-in Cohort 2 and Phase 2 Cohort 2: Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Up to 107 weeks | ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as determined at least 4 weeks after initial documentation of response by investigator assessment per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Clopper-Pearson estimates were used in outcome measure analysis. Percentages were rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0 | First dose date up to last dose date (up to 73 weeks) plus 30 days | Treatment-emergent laboratory abnormalities according to NCI CTCAE V5.0 are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days and prior to the day before initiation of subsequent anti-cancer therapy. Percentages were rounded off. |
| Phase 2 Cohort 1: Confirmed ORR as Determined by Investigator Assessment Per RECIST, Version 1.1 | Up to 107 weeks | ORR is defined as the percentage of participants who achieve a CR or PR that is confirmed at least 4 weeks after initial documentation of response, as measured by RECIST version 1.1, as determined by investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Clopper-Pearson estimates were used in outcome measure analysis. Percentages were rounded off. |
| Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab | Up to 73 weeks | — |
| Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Cohort 1: Predose - Day 1, 8, 22, 43, 85, 127, 190 and 253, Postdose 1 hour - Day 8 and 43; Cohort 2: Predose - Day 1, 8, 22, 43, 64, 85, 127, 190 and 253, Postdose 1 hour - Day 43 and 64 | — |
| Safety Run-in Cohort 2 and Phase 2 Cohort 2: PFS as Determined by Investigator Assessment Using RECIST Version 1.1 | Up to 107 weeks | PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1 | Up to 107 weeks | DOR is defined as time from first documentation of CR or PR to the earliest date of documented PD, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Overall Survival (OS) | Up to 107 weeks | OS is defined as time from date of randomization to death from any cause. |
| Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing TEAEs | First dose date up to last dose date (up to 73 weeks) plus 30 days | TEAEs are defined as any events not present prior to the study treatment, or any events already present but worsening in either intensity or frequency following exposure to the study treatment. TEAEs were any AEs with an onset date on or after the date of the first dose of study treatment up to 30 days after the date of the last dose of study treatment, or the day before initiation of subsequent anticancer therapy, whichever comes first. An AE is any untoward medical occurrence in a clinical study patient administered a study drug that does not necessarily have a causal relationship with the treatment. Percentages were rounded-off. |
Countries
Australia, Hong Kong, South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Republic of Korea, Taiwan, Australia, Hong Kong, United States, and the United Kingdom.
Pre-assignment details
129 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel Participants received magrolimab intravenous (IV) infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below in 28 days cycle:
* Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-day cycle for up to 72 weeks;
* Nab-paclitaxel 100 mg/m\^2 on Days 1, 8 and 15 of every 28-day cycle for up to 72 weeks.
Participants did not receive paclitaxel in the Safety Runi-in Cohort 1. | 8 |
| Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel Participants received magrolimab IV infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below in 28 days cycle:
* Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-day cycle for up to 70 weeks;
* Nab-paclitaxel 100 mg/m\^2 on Days 1, 8 and 15 of every 28-day cycle for up to 70 weeks or paclitaxel 90 mg/m\^2 on Days 1, 8 and 15 of every 28-day cycle for up to 34 weeks. | 14 |
| Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel Participants received nab-paclitaxel IV or paclitaxel IV as mentioned below:
* Nab-paclitaxel 100 mg/m\^2 on Days 1, 8 and 15 of every 28-day cycle for up to 54 weeks or paclitaxel 90 mg/m\^2 on Days 1, 8 and 15 of every 28-day cycle for up to 2.1 weeks. | 14 |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan Participants received magrolimab IV infusion + sacituzumab govitecan IV infusion as mentioned below:
* Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, Cycle 2 Days 1, 8, and 15; 60 mg/kg, on Cycle 3 Day 1 onwards for every 21-day cycle for up to 73 weeks;
* Sacituzumab govitecan 10 mg/kg on Days 1 and 8 onwards for every 21-day cycle for up to 73 weeks. | 13 |
| Phase 2 Cohort 2: Magrolimab + Sacituzumab Govitecan Participants received magrolimab IV infusion + sacituzumab govitecan IV infusion as mentioned below:
* Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, Cycle 2 Days 1, 8, and 15; 60 mg/kg, on Cycle 3 Day 1 onwards for every 21-day cycle for up to 48 weeks;
* Sacituzumab govitecan 10 mg/kg on Days 1 and 8 onwards for every 21-day cycle for up to 49 weeks. | 42 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Death | 2 | 3 | 4 | 5 | 5 |
| Overall Study | Investigator's discretion | 0 | 1 | 0 | 1 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 4 | 10 | 7 | 6 | 34 |
| Overall Study | Withdrew consent | 2 | 0 | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel | Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel | Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Phase 2 Cohort 2: Magrolimab + Sacituzumab Govitecan | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 2 Participants | 3 Participants | 6 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 12 Participants | 11 Participants | 5 Participants | 36 Participants | 74 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 12.8 | 52 years STANDARD_DEVIATION 13.3 | 53 years STANDARD_DEVIATION 10 | 54 years STANDARD_DEVIATION 11.5 | 53 years STANDARD_DEVIATION 11.2 | 54 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 14 Participants | 12 Participants | 8 Participants | 40 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 10 Participants | 2 Participants | 2 Participants | 29 Participants | 49 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 8 Participants | 5 Participants | 12 Participants | 34 Participants |
| Region of Enrollment Australia | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 0 Participants | 9 Participants |
| Region of Enrollment Hong Kong | 4 Participants | 4 Participants | 0 Participants | 2 Participants | 3 Participants | 13 Participants |
| Region of Enrollment South Korea | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 18 Participants | 24 Participants |
| Region of Enrollment Taiwan | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 7 Participants | 10 Participants |
| Region of Enrollment United Kingdom | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 5 Participants | 3 Participants | 7 Participants | 2 Participants | 12 Participants | 29 Participants |
| Sex: Female, Male Female | 13 Participants | 14 Participants | 13 Participants | 8 Participants | 41 Participants | 89 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 8 | 3 / 14 | 4 / 14 | 6 / 13 | 5 / 43 |
| other Total, other adverse events | 8 / 8 | 14 / 14 | 13 / 13 | 13 / 13 | 41 / 42 |
| serious Total, serious adverse events | 5 / 8 | 4 / 14 | 4 / 13 | 6 / 13 | 7 / 42 |
Outcome results
Primary
Phase 2 Cohort 1: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS was defined as the time from the date of randomization until the earliest date of documented disease progression (PD), as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (KM) estimates were used in outcome measure analysis.
Time frame: Up to 107 weeks
Population: Participants from Phase 2 Cohort 1 in the Intent-to-treat (ITT) Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Phase 2 Cohort 1: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 13.9 months |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 10.0 months |
p-value: 0.161795% CI: [0.147, 1.409]Log Rank
Primary
Safety Run-in Cohort 2 and Phase 2 Cohort 2: Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as determined at least 4 weeks after initial documentation of response by investigator assessment per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Clopper-Pearson estimates were used in outcome measure analysis. Percentages were rounded off.
Time frame: Up to 107 weeks
Population: Participants in the modified Intent-To-Treat (mITT) Analysis Set (Cohort 2) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Safety Run-in Cohort 2 and Phase 2 Cohort 2: Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 30.8 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Safety Run-in Cohort 2 and Phase 2 Cohort 2: Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 38.1 percentage of participants |
Primary
Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)
A DLT is defined as any: * Grade 3 or higher hematologic toxicity including: * Hemolytic anemia that is medically significant, requiring hospitalization or prolongation of existing hospitalization, disabling, or limiting self-care activities of daily life. * Event meeting Hy's Law criteria: * Treatment-emergent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation (at least 3 x ULN), AND * Treatment-emergent total bilirubin elevation (more than 2 x ULN), and absence of cholestasis (defined as alkaline phosphatase less than 2 x ULN), AND * No other good explanation for the injury (hepatitis A, B, C, or other viral hepatic injury, alcohol ingestion, congestive heart failure, worsening liver metastases). * Grade 3 or higher nonhematologic toxicity that has worsened in severity from pretreatment baseline during the DLT assessment period, and in the opinion of the investigator, the AE is at least possibly related to magrolimab.
Time frame: First dose date up to 28 days (Cohort 1) and up to 21 days (Cohort 2)
Population: DLT-Evaluable Analysis Set included all participants who meet 1 of the following criteria:~* Participant experienced a DLT at any time after initiation of the first infusion of magrolimab.~* Participant did not experience a DLT and completed at least 3 infusions of magrolimab (28-day cycle), and at least 2 doses of nab-paclitaxel or paclitaxel (Safety Run-in Cohort 1 (SRiC1)), at least 2 infusions of magrolimab (21-day cycle), and at least 2 infusions of sacituzumab govitecan (SRiC2).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 percentage of participants |
Primary
Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
TEAEs are defined as any events not present prior to the study treatment, or any events already present but worsening in either intensity or frequency following exposure to the study treatment. TEAEs were any AEs with an onset date on or after the date of the first dose of study treatment up to 30 days after the date of the last dose of study treatment, or the day before initiation of subsequent anticancer therapy, whichever comes first. An AE is any untoward medical occurrence in a clinical study patient administered a study drug that does not necessarily have a causal relationship with the treatment.
Time frame: First dose date up to last dose date (up to 73 weeks) plus 30 days
Population: The Safety Analysis Set in the Safety Run-in Cohorts 1 and 2 included all participants who took at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
Primary
Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0
Treatment-emergent laboratory abnormalities according to NCI CTCAE V5.0 are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days and prior to the day before initiation of subsequent anti-cancer therapy. Grade 1 mild, Grade 2 moderate, Grade 3 severe, Grade 4 life-threatening and Grade 5 death. Percentages were rounded off.
Time frame: First dose date up to last dose date (up to 73 weeks) plus 30 days
Population: Participants in the Safety Run-in Cohorts 1 and 2 in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 | Any Grade | 100.0 percentage of participants |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 | Grade 3 or 4 | 62.5 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 | Grade 3 or 4 | 84.6 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 | Any Grade | 100.0 percentage of participants |
Secondary
Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time
Time frame: Cohort 1: Predose - Day 1, 8, 22, 43, 85, 127, 190 and 253, Postdose 1 hour - Day 8 and 43; Cohort 2: Predose - Day 1, 8, 22, 43, 64, 85, 127, 190 and 253, Postdose 1 hour - Day 43 and 64
Population: Participants in the Pharmacokinetic (PK) Analysis set with available data were analyzed. The PK Analysis Set included all participants who received any amount of magrolimab and have at least 1 evaluable post-treatment serum concentration of magrolimab.~PK of magrolimab was evaluated in 2 combination therapy cohorts: Cohort 1 (Safety Run-in Cohort 1, and Phase 2 Cohort 1 Arm A), and Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2). The combined PK data were summarized and reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 8 Predose | 0.0700 μg/mL | Standard Deviation 0.263 |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 43 Predose | 862 μg/mL | Standard Deviation 322 |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 85 Predose | 394 μg/mL | Standard Deviation 178 |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 8 1-Hour Postdose | 289 μg/mL | Standard Deviation 164 |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 127 Predose | 303 μg/mL | Standard Deviation 77.3 |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 43 1-Hour Postdose | 1520 μg/mL | Standard Deviation 415 |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 190 Predose | 263 μg/mL | Standard Deviation 124 |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 22 Predose | 559 μg/mL | Standard Deviation 218 |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 253 Predose | 294 μg/mL | Standard Deviation 65.8 |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 1 Predose | NA μg/mL | — |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 190 Predose | 373 μg/mL | Standard Deviation 272 |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 253 Predose | 498 μg/mL | Standard Deviation 112 |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 1 Predose | NA μg/mL | — |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 8 Predose | NA μg/mL | — |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 22 Predose | 306 μg/mL | Standard Deviation 129 |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 43 Predose | 585 μg/mL | Standard Deviation 193 |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 43 1-Hour Postdose | 1670 μg/mL | Standard Deviation 592 |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 64 Predose | 490 μg/mL | — |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 64 1-Hour Postdose | 424 μg/mL | — |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 85 Predose | 414 μg/mL | Standard Deviation 188 |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time | Day 127 Predose | 382 μg/mL | Standard Deviation 148 |
Secondary
Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab
Time frame: Up to 73 weeks
Population: Participants in the Immunogenicity Analysis Set with available data were analyzed. The Immunogenicity Analysis Set included all participants who received any amount of magrolimab and have at least 1 evaluable anti-magrolimab antibody test results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab | ADA Prevalence | 12.5 percentage of participants |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab | ADA Incidence | 0.0 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab | ADA Incidence | 0.0 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab | ADA Prevalence | 7.1 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab | ADA Incidence | 0.0 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab | ADA Prevalence | 15.4 percentage of participants |
| Phase 2 Cohort 2: Magrolimab + Sacituzumab Govitecan | Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab | ADA Prevalence | 4.8 percentage of participants |
| Phase 2 Cohort 2: Magrolimab + Sacituzumab Govitecan | Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab | ADA Incidence | 0.0 percentage of participants |
Secondary
Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0
Treatment-emergent laboratory abnormalities according to NCI CTCAE V5.0 are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days and prior to the day before initiation of subsequent anti-cancer therapy. Percentages were rounded off.
Time frame: First dose date up to last dose date (up to 73 weeks) plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0 | Any Grade | 100.0 percentage of participants |
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0 | Grade 3 or 4 | 64.3 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0 | Any Grade | 84.6 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0 | Grade 3 or 4 | 7.7 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0 | Any Grade | 100.0 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0 | Grade 3 or 4 | 78.6 percentage of participants |
Secondary
Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing TEAEs
TEAEs are defined as any events not present prior to the study treatment, or any events already present but worsening in either intensity or frequency following exposure to the study treatment. TEAEs were any AEs with an onset date on or after the date of the first dose of study treatment up to 30 days after the date of the last dose of study treatment, or the day before initiation of subsequent anticancer therapy, whichever comes first. An AE is any untoward medical occurrence in a clinical study patient administered a study drug that does not necessarily have a causal relationship with the treatment. Percentages were rounded-off.
Time frame: First dose date up to last dose date (up to 73 weeks) plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing TEAEs | 100.0 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing TEAEs | 100.0 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing TEAEs | 97.6 percentage of participants |
Secondary
Phase 2 Cohort 1: Confirmed ORR as Determined by Investigator Assessment Per RECIST, Version 1.1
ORR is defined as the percentage of participants who achieve a CR or PR that is confirmed at least 4 weeks after initial documentation of response, as measured by RECIST version 1.1, as determined by investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Clopper-Pearson estimates were used in outcome measure analysis. Percentages were rounded off.
Time frame: Up to 107 weeks
Population: Participants from the Phase 2 Cohort 1 in the ITT Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Phase 2 Cohort 1: Confirmed ORR as Determined by Investigator Assessment Per RECIST, Version 1.1 | 35.7 percentage of participants |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1: Confirmed ORR as Determined by Investigator Assessment Per RECIST, Version 1.1 | 21.4 percentage of participants |
95% CI: [0.379, 10.938]
Secondary
Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1
DOR is defined as time from first documentation of CR or PR to the earliest date of documented PD, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Up to 107 weeks
Population: Participants in the ITT Analysis Set (Cohort 1) and mITT Analysis Set (Cohort 2) with objective response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1 | 12.2 months |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1 | NA months |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1 | NA months |
| Phase 2 Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1 | NA months |
Secondary
Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Overall Survival (OS)
OS is defined as time from date of randomization to death from any cause.
Time frame: Up to 107 weeks
Population: Participants in the ITT Analysis Set (Cohort 1) and mITT Analysis Set (Cohort 2) were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Overall Survival (OS) | NA months |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Overall Survival (OS) | NA months |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Overall Survival (OS) | 15.7 months |
| Phase 2 Cohort 2: Magrolimab + Sacituzumab Govitecan | Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Overall Survival (OS) | NA months |
Secondary
Safety Run-in Cohort 2 and Phase 2 Cohort 2: PFS as Determined by Investigator Assessment Using RECIST Version 1.1
PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Up to 107 weeks
Population: Participants in the mITT Analysis Set (Cohort 2) were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel | Safety Run-in Cohort 2 and Phase 2 Cohort 2: PFS as Determined by Investigator Assessment Using RECIST Version 1.1 | 7.1 months |
| Safety Run-in Cohort 2: Magrolimab + Sacituzumab Govitecan | Safety Run-in Cohort 2 and Phase 2 Cohort 2: PFS as Determined by Investigator Assessment Using RECIST Version 1.1 | 5.5 months |