Study of ASP0739 Alone and With Pembrolizumab in Advanced Solid Tumors With NY-ESO-1 Expression Participants
- Registration Number
- NCT04939701
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 16
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).
-
Participant has R/R solid tumor (melanoma, non-small cell lung cancer [NSCLC]-adenocarcinoma and squamous cell, or esophageal squamous cell carcinoma [ESCC]) after available SOC treatment or is not a candidate for SOC therapy (single-agent only).
-
Participant consents to provide an archival tumor specimen in a tissue block or unstained serial slides prior to IP administration.
-
Participant in phase 2 consents to provide tumor specimen obtained within 56 days prior to first dose of study treatment, as tissue block or unstained serial slides.
-
Participant in phase 2 consents to undergoing a tumor biopsy (core needle biopsy or excision) during the treatment period.
-
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
-
Participant with life expectancy of >= 12 weeks at the time of screening.
-
Participant must meet criteria for clinical laboratory tests during screening period.
-
A female participant is eligible to participate if she is not pregnant and at least one of the following conditions apply:
- Not a woman of childbearing potential (WOCBP) OR
- WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final investigational product (IP) administration.
-
Female participant must not be breastfeeding at screening or during the study period and for 6 months after the final IP administration.
-
Female participant must not donate ova at screening and throughout the study period and for 6 months after the final IP administration.
-
A male participant with female partner(s) of childbearing potential must agree to use contraception during the treatment period and for at least 6 months after the final IP administration.
-
Male participant must not donate sperm starting at screening and throughout the study period and for 6 months after the final IP administration.
-
Participant agrees not to participate in another interventional study while on treatment.
-
Participant measurable disease according to RECIST 1.1. For participant with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
-
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.
-
Participant has known history of serious hypersensitivity reaction to a known ingredient of ASP0739 or pembrolizumab or severe hypersensitivity reaction to treatment with another monoclonal antibody.
-
Participant has a prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years prior to screening visit, except for locally curable malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
-
Participant has received a prior allogeneic bone marrow or solid organ transplant.
-
Participant has an active uncontrolled infection within 14 days of treatment.
-
Participant is known to have human immunodeficiency virus infection.
-
Participant has active hepatitis B or C or other active hepatic disorder or participant is on hepatitis treatment. Hepatitis C RNA testing is not required in participants with negative hepatitis C antibody testing.
-
Participant has any condition which makes the participant unsuitable for study participation.
-
Participant has had a major surgical procedure and has not completely recovered within 28 days prior to the start of study treatment.
-
Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of study treatment or currently has an uncontrolled illness including, but not limited to, symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
-
Participant is expected to require another form of anti-cancer therapy while on study treatment.
-
Participant has a known or suspected hypersensitivity to bovine-derived protein or has suspected hypersensitivity to any ingredients of ASP0739.
Additional Exclusion Criteria for Participants in Combination Therapy Cohorts
- Participants with a history of myocarditis or congestive heart failure (as defined by New York Heart Associated Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry.
- Participants with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.
- Participants with baseline pulse oximetry < 92% "on Room air."
- Participants must not have known microsatellite instability-high or deficient MisMatch Repair.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion (Phase 2): ASP0739 1x10^8 cells/mL ASP0739 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). Dose Escalation (Phase 1): ASP0739 1x10^8 cells/mL ASP0739 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). Dose Escalation (Phase 1): ASP0739 1x10^7 cells/mL ASP0739 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). .
- Primary Outcome Measures
Name Time Method Number of Participants With ECOG Performance Status at C1D8 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 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 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) 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 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) 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 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 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 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 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 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 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 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 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 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 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) 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 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 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 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 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 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 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 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 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 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 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 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 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 Outcome Measures
Name Time Method Progression-Free Survival Per RECIST v1.1 (PFS) by Investigator Assessment From first dose up to 525 days 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
Duration of Response Per RECIST (DOR) v1.1 From first response up to 525 days 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.Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (ORR) by Investigator Assessment From first dose up to 525 days 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.Disease Control Rate Per iRECIST (iDCR) by Investigator Assessment From first dose up to 525 days 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.iPFS Per iRECIST by Investigator Assessment From first dose up to 525 days 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.Disease Control Rate Per RECIST v1.1 (DCR) by Investigator Assessment From first dose up to 525 days 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.Progression-Free Survival Per iRECIST (iPFS) by Independent Central Review From first dose up to 525 days 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.Duration of Overall Survival (OS) From first dose up to 525 days 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).
ORR Per iRECIST (iORR) by Investigator Assessment 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 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.Duration of Response Per iRECIST (iDOR) From first response up to 525 days 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.
Trial Locations
- Locations (6)
NYU Perlmutter Cancer Center
🇺🇸New York, New York, United States
Northwestern University Robert H. Lurie Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
The University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
City of Hope
🇺🇸Duarte, California, United States
Brown University
🇺🇸Providence, Rhode Island, United States
University of Miami
🇺🇸Miami, Florida, United States