A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP0739 as a Single Agent and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors Known to Express NY-ESO-1
Overview
- Phase
- Phase 1
- Intervention
- ASP0739
- Conditions
- Ovarian Cancer
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 16
- Locations
- 6
- Primary Endpoint
- Number of Participants With ECOG Performance Status at C1D8
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Phase 1 Dose Escalation only:
- •Participant has relapsed/refractory (R/R) solid tumor known to express NY-ESO-1 after completing available Standard of Care (SOC) therapy or is not a candidate for SOC therapy. NY-ESO-1 expression status is not required for participant entry.
- •Safety Lead-in, Phase 2 Single agent and Combination Therapy only:
- •Participant has relapsed/refractory (R/R) synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCL) disease after undergoing available SOC treatment or is not a candidate for SOC therapy (must have previously received either an anthracycline or ifosfamide containing regimen or another systemic regimen, if not a candidate for either agent).
- •Participant has not received prior checkpoint inhibitor therapy (i.e., Programmed Cell Death Protein 1 \[PD-1\]/Programmed Death Ligand 1 \[PD-L1\] treatment naive)
- •SS: confirmation by the presence of a translocation between SYT on the X chromosome and SSX1, SSX2, or SSX4 on chromosome 18 (may be presented in the pathology report as t \[X;18\]).
- •MRCL: confirmation by the presence of the reciprocal chromosomal translocation t (12;16) (q13;p11) or t(12;22)(q13;q12).
- •Participant has R/R ovarian cancer that is:
- •platinum resistant OR platinum-sensitive, but the participant is not a candidate for platinum or other SOC therapy.
- •Participant has not received prior checkpoint inhibitor therapy (i.e., naive PD-1/PD-L1 treatment participants).
Exclusion Criteria
- •Participant has persistent non-hematological toxicities of \>= grade 2 (National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 5.0), with symptoms and objective findings from treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation or surgery).
- •Participant has received any of the following therapies (for inclusion in the study, all abnormalities must have returned to \<= grade 1):
- •Systemic immunomodulators (checkpoint inhibitors)-except the dose escalation phase and the NY-ESO-1 solid tumor (melanoma, NSCLC-adenocarcinoma and squamous cell and ESCC) cohorts in the dose expansion phase of monotherapy, which may have received prior checkpoint inhibitor therapy
- •Immunosuppressive drugs including steroids \<= 14 days prior to treatment
- •Cytotoxic agents \<= 14 days prior to treatment
- •Investigational agent \<= 21 days prior to treatment or 5 half-lives, whichever is shorter
- •Radiation therapy \<= 21 days prior to treatment
- •Participant has clinically active or untreated nervous system metastases. Participants with previously treated Central Nervous System (CNS) metastases are eligible, if they are clinically stable and have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study treatment and are not requiring immunosuppressive doses of systemic steroids (\> 30 mg per day of hydrocortisone or \> 10 mg per day of prednisone or equivalent) for longer than 2 weeks.
- •Participant has an active autoimmune disease. Participant with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy, or skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment are allowed.
- •Participant was discontinued from prior immunomodulatory therapy due to a grade \>= 3 toxicity that was mechanistically related (e.g., immune related) to the agent.
Arms & Interventions
Dose Escalation (Phase 1): ASP0739 1x10^7 cells/mL
Participants with Relapsed/Refractory (R/R) solid tumors known to express New York esophageal squamous cell carcinoma 1 (NY-ESO-1) received intravenous (IV) infusion of ASP0739 (human embryonic kidney cell \[HEK293\] transfected with a lentiviral vector that is encoding the target antigen NY-ESO-1) at a dose of 1x10\^7 cells/milliliters (mL) at 4 to 6 mL/minute infusion rate on day 1 of each cycle for a total of 4 doses; an additional 2 doses was administered in participants with a partial response (PR) or stable disease (SD) (1 cycle= 28 days). .
Intervention: ASP0739
Dose Escalation (Phase 1): ASP0739 1x10^8 cells/mL
Participants with R/R solid tumors known to express NY-ESO-1 received IV infusion of ASP0739 (HEK293 transfected with a lentiviral vector that is encoding the target antigen NY-ESO-1) at a dose of 1x10\^8 cells/mL at 4 to 6 mL/minute infusion rate on day 1 of each cycle for a total of 4 doses; an additional 2 doses was administered in participants with a PR or SD (1 cycle= 28 days).
Intervention: ASP0739
Dose Expansion (Phase 2): ASP0739 1x10^8 cells/mL
Participants with synovial sarcoma (SS), myxoid/round cell liposarcoma (MRCL), ovarian cancer and other solid tumors known to express NY-ESO-1 (melanoma, non-small cell lung cancer \[NSCLC\] adenocarcinoma and squamous cell and esophageal squamous cell carcinoma \[ESCC\]) received IV infusion of ASP0739 (HEK293 transfected with a lentiviral vector that is encoding the target antigen NY-ESO-1) at a dose of 1x10\^8 cells/mL at 4 to 6 mL/minute infusion rate on day 1 of each cycle for a total of 4 doses; an additional 2 doses was administered in participants with a PR or SD (1 cycle= 28 days).
Intervention: ASP0739
Outcomes
Primary Outcomes
Number of Participants With ECOG Performance Status at C1D8
Time Frame: 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.
Number of Participants With ECOG Performance Status at CID22
Time Frame: 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.
Number of Participants With ECOG Performance Status at C2D1
Time Frame: 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.
Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Cycle 1 Day 1 (C1D1) up to C1D28
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.
Number of Participants With ECOG Performance Status at C2D15
Time Frame: 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) & Serious Adverse Events (SAEs)
Time Frame: From first dose up to 198 days
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.
Number of Participants With ECOG Performance Status at CID15
Time Frame: 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.
Number of Participants With ECOG Performance Status at C2D8
Time Frame: 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.
Number of Participants With ECOG Performance Status at C3D22
Time Frame: 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.
Number of Participants With ECOG Performance Status at C4D15
Time Frame: 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.
Number of Participants With ECOG Performance Status at C4D22
Time Frame: 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.
Number of Participants With ECOG Performance Status at C1D2
Time Frame: 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.
Number of Participants With ECOG Performance Status at C2D2
Time Frame: 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.
Number of Participants With ECOG Performance Status at C3D8
Time Frame: 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.
Number of Participants With ECOG Performance Status at C4D1
Time Frame: 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.
Number of Participants With ECOG Performance Status at Safety Follow up 60 Days
Time Frame: At 60 days safety follow up (day 228)
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.
Recommended Phase 2 Dose (RP2D)
Time Frame: C1D1 up to C1D28
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.
Number of Participants With ECOG Performance Status at C4D8
Time Frame: 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.
Number of Participants With ECOG Performance Status at C2D22
Time Frame: 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.
Number of Participants With ECOG Performance Status at C3D1
Time Frame: 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.
Number of Participants With ECOG Performance Status at C3D15
Time Frame: 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.
Number of Participants With ECOG Performance Status at C5D1
Time Frame: 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.
Number of Participants With ECOG Performance Status at C5D15
Time Frame: 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.
Number of Participants With ECOG Performance Status at C6D15
Time Frame: 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.
Number of Participants With ECOG Performance Status at Safety Follow up 30 Days
Time Frame: At 30 days safety follow up (day 198)
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.
Number of Participants With ECOG Performance Status at Safety Follow up 90 Days
Time Frame: At 90 days safety follow up (day 258)
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.
Number of Participants With ECOG Performance Status at C6D1
Time Frame: 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.
Number of Participants With ECOG Performance Status at End of Treatment (EOT) Visit
Time Frame: At EOT visit (day 175)
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.
Objective Response Rate Per Immune Response Evaluation Criteria in Solid Tumors (iRECIST) (iORR) by Independent Central Review
Time Frame: From first dose up to 525 days
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.
Secondary Outcomes
- Progression-Free Survival Per RECIST v1.1 (PFS) by Investigator Assessment(From first dose up to 525 days)
- Duration of Response Per RECIST (DOR) v1.1(From first response up to 525 days)
- Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (ORR) by Investigator Assessment(From first dose up to 525 days)
- Disease Control Rate Per iRECIST (iDCR) by Investigator Assessment(From first dose up to 525 days)
- iPFS Per iRECIST by Investigator Assessment(From first dose up to 525 days)
- Disease Control Rate Per RECIST v1.1 (DCR) by Investigator Assessment(From first dose up to 525 days)
- Progression-Free Survival Per iRECIST (iPFS) by Independent Central Review(From first dose up to 525 days)
- Duration of Overall Survival (OS)(From first dose up to 525 days)
- ORR Per iRECIST (iORR) by Investigator Assessment(From first dose up to 525 days)
- Duration of Response Per iRECIST (iDOR)(From first response up to 525 days)