The purpose of this study was to evaluate the safety, and tolerability of ASP0739, when administered as a single agent and in combination with pembrolizumab. This study also evaluated the clinical response and other measures of anticancer activity of ASP0739 when administered as a single agent and in combination with pembrolizumab based on central and local assessment.
The study comprised of 2 phases. Phase 1 (dose escalation) included participants with solid tumors known to express New York esophageal squamous cell carcinoma 1 (NY-ESO-1). Phase 2 (ASP0739 as single agent and in combination with pembrolizumab) included participants with relapsed/refractory Synovial Sarcoma (SS), myxoid/round cell liposarcoma (MRCL), and ovarian cancer who had not responded to Standard of Care (SOC) or were ineligible for standard therapy. Phase 2 single agent also included a cohort of participants with select solid tumors known to express NY-ESO-1 (melanoma, Non Small Cell Lung Cancer-adenocarcinoma \[NSCLC\], squamous cell and esophageal squamous cell carcinoma \[ESCC\]). Japanese participants were only enrolled into the monotherapy arm of the dose expansion cohort.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Intravenous (IV)
City of Hope
Duarte, California, United States
University of Miami
Miami, Florida, United States
Northwestern University Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States
The University of Chicago Medicine
Chicago, Illinois, United States
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as any event occurring within 28 days of first dose on C1D1 and graded as: * Grade (GR) ≥2 autoimmune reaction * GR 3 Immune related AEs (irAEs) that did not resolve to GR ≤1 in 3 to 5 days, febrile neutropenia with or without infection, thrombocytopenia with bleeding requiring transfusion, anemia requiring transfusion * GR 4 irAEs, neutropenia, thrombocytopenia, anemia * GR ≥3 non-hematological AE that did not resolve to GR ≤2 within 72 hours of onset, liver function test abnormality lasting ≥7 days Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5 × upper limit of normal (ULN; GR≥3) without liver metastases and 8 × ULN in participants with liver metastases, AST or ALT \>3 × ULN and total bilirubin (TBL) \>2 × ULN (in participants with, Gilbert syndrome: AST or ALT \>3 × ULN and direct bilirubin \>1.5) (confirmed Hy's Law) * GR 5 toxicity, Prolonged delay (\>2 weeks) in initiating cycle 2 due to treatment-related toxicity.
Time frame: Cycle 1 Day 1 (C1D1) up to C1D28
Number of Participants With Treatment Emergent Adverse Events (TEAEs) & Serious Adverse Events (SAEs)
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An AE was considered "serious" if, it resulted in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly, or birth defect; requires inpatient hospitalization; or leads to prolongation of hospitalization; other medically important events. A treatment-emergent adverse event (TEAE) was defined as an AE observed after the date of first dose until 30 days after the last dose.
Time frame: From first dose up to 198 days
Number of Participants With ECOG Performance Status at C1D2
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
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NYU Perlmutter Cancer Center
New York, New York, United States
Brown University
Providence, Rhode Island, United States
Time frame: At C1D2
Number of Participants With ECOG Performance Status at C1D8
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C1D8
Number of Participants With ECOG Performance Status at CID15
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At CID15
Number of Participants With ECOG Performance Status at CID22
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At CID22
Number of Participants With ECOG Performance Status at C2D1
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C2D1
Number of Participants With ECOG Performance Status at C2D2
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C2D2
Number of Participants With ECOG Performance Status at C2D8
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C2D8
Number of Participants With ECOG Performance Status at C2D15
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C2D15
Number of Participants With ECOG Performance Status at C2D22
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C2D22
Number of Participants With ECOG Performance Status at C3D1
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C3D1
Number of Participants With ECOG Performance Status at C3D8
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C3D8
Number of Participants With ECOG Performance Status at C3D15
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C3D15
Number of Participants With ECOG Performance Status at C3D22
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C3D22
Number of Participants With ECOG Performance Status at C4D1
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C4D1
Number of Participants With ECOG Performance Status at C4D8
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C4D8
Number of Participants With ECOG Performance Status at C4D15
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C4D15
Number of Participants With ECOG Performance Status at C4D22
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C4D22
Number of Participants With ECOG Performance Status at C5D1
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C5D1
Number of Participants With ECOG Performance Status at C5D15
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C5D15
Number of Participants With ECOG Performance Status at C6D1
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C6D1
Number of Participants With ECOG Performance Status at C6D15
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At C6D15
Number of Participants With ECOG Performance Status at End of Treatment (EOT) Visit
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead. EOT visit was 7 days after last dose.
Time frame: At EOT visit (day 175)
Number of Participants With ECOG Performance Status at Safety Follow up 30 Days
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At 30 days safety follow up (day 198)
Number of Participants With ECOG Performance Status at Safety Follow up 60 Days
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At 60 days safety follow up (day 228)
Number of Participants With ECOG Performance Status at Safety Follow up 90 Days
The ECOG Scale was used to assess performance status. Grade Description: 0 - Fully active, able to carry on all pre disease performance without restriction. 1. \- Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. \- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. -Dead.
Time frame: At 90 days safety follow up (day 258)
Recommended Phase 2 Dose (RP2D)
The dose recommended for use in phase 2 studies was analyzed on the basis of the safety, tolerability, and preliminary pharmacokinetic (PK) and efficacy data obtained in phase 1 studies.
Time frame: C1D1 up to C1D28
Objective Response Rate Per Immune Response Evaluation Criteria in Solid Tumors (iRECIST) (iORR) by Independent Central Review
iORR was defined as the percentage of participants for each dose level whose best overall response is rated as complete response (iCR) or partial response (iPR) per iRECIST. iORR assessments included: * iORR with confirmed response * iORR with unconfirmed response iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
Time frame: From first dose up to 525 days
Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (ORR) by Investigator Assessment
ORR was defined as the percentage of participants for each dose level whose best overall response is rated as CR or PR per RECIST v1.1. ORR assessment included: ORR with confirmed response ORR with unconfirmed response Participants who had CR or PR were considered to have confirmed response, and participants who did not meet this criterion were considered to have unconfirmed response. CR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
Time frame: From first dose up to 525 days
Disease Control Rate Per iRECIST (iDCR) by Investigator Assessment
iDCR was defined as the percentage of participants for each dose level whose best overall response is rated as confirmed and unconfirmed iCR, iPR or stable disease (iSD) per iRECIST. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. SD was defined as neither sufficient shrinkage to qualify for iPR nor sufficient increase to qualify for progressive disease. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. Participants who had CR or PR were considered to have confirmed response, and participants who did not meet this criterion were considered to have unconfirmed response.
Time frame: From first dose up to 525 days
Disease Control Rate Per RECIST v1.1 (DCR) by Investigator Assessment
DCR is defined as the percentage of participants for each dose level whose best overall response is rated as confirmed CR, PR or SD per RECIST v1.1.CR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 mm in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time frame: From first dose up to 525 days
Progression-Free Survival Per iRECIST (iPFS) by Independent Central Review
iPFS is defined as the time from the date of first dose until death from any cause or radiographic disease progression assessed per iRECIST by independent central review. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time frame: From first dose up to 525 days
iPFS Per iRECIST by Investigator Assessment
iPFS is defined as the time from the date of first dose until death from any cause or radiographic disease progression assessed per iRECIST by investigator assessment. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time frame: From first dose up to 525 days
Progression-Free Survival Per RECIST v1.1 (PFS) by Investigator Assessment
PFS is defined as the time from the date of first dose until death from any cause or radiographic disease progression assessed per RECIST v1.1 by investigator assessment.Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started
Time frame: From first dose up to 525 days
Duration of Overall Survival (OS)
OS is defined as the time from the date of first dose until the date of death from any cause (death date - first dose date + 1). For a participant who is not known to have died by the end of study follow-up, OS is censored at the date of last contact (date of last contact - first dose date + 1).
Time frame: From first dose up to 525 days
Duration of Response Per iRECIST (iDOR)
iDOR as per iRECIST was defined as the time from the date of the first response iCR/iPR (whichever is first recorded) to the date of radiographical progression or date of censoring. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
Time frame: From first response up to 525 days
Duration of Response Per RECIST (DOR) v1.1
DOR as per RECIST 1.1 was defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression or date of censoring. CR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 mm in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
Time frame: From first response up to 525 days
ORR Per iRECIST (iORR) by Investigator Assessment
iORR was defined as the percentage of participants for each dose level whose best overall response is rated as iCR or iPR per iRECIST. iORR assessments included: * iORR with confirmed response * iORR with unconfirmed response iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Participants who had CR or PR were considered to have confirmed response, and participants who did not meet this criterion were considered to have unconfirmed response.
Time frame: From first dose up to 525 days