Incurable Platinum Refractory Germ Cell Tumors, Tumors
Conditions
Keywords
Incurable Platinum Refractory Germ Cell Tumors, ASP1650
Brief summary
The purpose of this study was to establish the recommended phase 2 dose (RP2D) of ASP1650 (Safety Lead-in Phase), as well as, evaluate the efficacy of ASP1650 as measured by confirmed objective response rate (ORR) (phase 2) in participants with incurable platinum refractory germ cell tumors. This study also evaluated the following efficacy measures for confirmed objective response rate (ORR); clinical benefit rate (CBR); duration of response (DOR); and progression-free survival (PFS); as well as safety and tolerability; the effect of ASP1650 on changes in serum beta human chorionic gonadotropin (βhCG) and alpha-fetoprotein (AFP); and the pharmacokinetics of ASP1650.
Detailed description
The study consisted of 2 phases: Safety Lead-in phase and phase 2. 19 participants were enrolled in both phases. The Safety Lead-in phase of this study was to establish the tolerability of RP2D. The RP2D determination was based on at least 6 evaluable participants at the RP2D as determined by the Dose Evaluation Committee (DEC). Once RP2D had been established as tolerable, 13 additional participants were enrolled in phase 2 to receive ASP1650 for up to a maximum of 12 cycles or until a study discontinuation criteria had been met, whichever occurred earlier.
Interventions
DRUGASP1650
Participants received ASP1650 dose level 1 or dose level 2 as intravenous infusion, Q2W starting on C1D1 for up to a maximum of 12 cycles or until study discontinuation criterion was met, whichever occurred earlier. Duration of each treatment cycle was 14 days.
Sponsors
Astellas Pharma Global Development, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration. * Subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration. * A male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study treatment administration. * Subject agrees not to participate in another interventional study while receiving study drug in present study. Disease Specific Criteria: * Subject has histological evidence of germ cell tumor. * Subject must have a germ cell tumor that is not amenable to cure with either surgery or chemotherapy. * Subjects with seminoma and non-seminoma are eligible. * Subject must have received initial cisplatin based combination chemotherapy AND demonstrated progression following at least 1 salvage regimen for advanced germ cell neoplasm (including relapsed primary mediastinal nonseminomatous germ cell tumor). 1. Initial cisplatin based combination therapy includes bleomycin-etoposide-cisplatin, cisplatin-etoposide, etoposide-ifosfamide-cisplatin or similar regimens. 2. Salvage regimens include high dose chemotherapy, paclitaxel-ifosfamide-cisplatin, vinblastine-ifosfamide cisplatin or similar regimens 3. Failure of prior therapy is defined as: A \> 25% increase in the products of perpendicular diameters of measurable tumor masses during prior therapy, which are not amenable to surgical resection; OR the presence of new tumor that are not amenable to surgical resection; OR an increase in alpha-fetoprotein (AFP) or beta human chorionic gonadotropin (βhCG) (≥ 50% increase in 2 separate samples collected at least 1 week apart are required if rising tumor markers are the only evidence of failure). NOTE: Subjects with clinically growing teratoma (enlarging mature teratoma arising during or after chemotherapy for a non seminomatous germ-cell tumor and with normal serum levels of AFP and βhCG) should undergo surgical resection if feasible. * Subjects with late relapse (\> 2 years) not amenable to resection are eligible. * Subjects must have evidence of recurrent or metastatic carcinoma by 1 or more of the following: 1. Subject has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within 28 days prior to the first dose of study treatment. For subjects 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. 2. Subject has a baseline rising tumor marker (AFP or βhCG). NOTE: If a rising tumor marker is the only evidence of progressive disease, at least 2 consecutive rising values at least 1 week apart are needed. Subjects with only evidence of disease as rising tumor marker AFP and βhCG will be assessed for alternate causes of increased serum levels of these markers, such as cross reaction with luteinizing hormone (LH) (can be tested if needed by testosterone suppression of LH), hepatitis, use of marijuana or second primary tumor. Physical or Laboratory Findings: * Subject must have an available tumor specimen in a tissue block or unstained serial slides, or subject is an appropriate candidate for tumor biopsy and is amenable to undergoing a tumor biopsy during the screening period. * Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Subject must meet all of the following criteria based on the centrally analyzed laboratory tests within 14 days prior to the first dose of study treatment. If repeat screening labs are required, local laboratory results can be used to confirm eligibility. In case of multiple central laboratory data within this period, the most recent data should be used to determine eligibility. 1. Hemoglobin ≥ 8 g/dL 2. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L 3. Platelets ≥ 75 x 109/L 4. Albumin ≥ 2.5 g/dL 5. Total bilirubin ≤ 2 x upper limit of normal (ULN) or direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 2 x ULN 6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present) 7. Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 8. Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 2 x ULN (except for subjects receiving anticoagulation therapy)
Exclusion criteria
Prohibited Treatment or Therapies: * Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subject using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone) is eligible. Subject who received systemic steroids for asymptomatic central nervous system (CNS) metastases within 14 days prior to first dose of study treatment is eligible. * Subject has received other investigational agents or devices within 28 days prior to first dose of study treatment. * Subject has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse event (AE) due to monoclonal antibody (mAb) agents administered more than 4 weeks earlier. * Subject has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 2 or at baseline) from AEs due to a previously administered agent. Medical History or Concurrent Disease: * Subject has prior severe allergic reaction or intolerance to a monoclonal antibody, including humanized or chimeric antibodies requiring permanent discontinuation. * Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment. * Subject has an active human immunodeficiency virus (HIV) infection or known active hepatitis B (HBsAg) or C infection. Subjects with well-controlled HIV infections (i.e., without detectable viral load) are eligible. For subjects who are negative for HBsAg, but hepatitis B core antibody (HBcAb) positive, an HBsAg deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded. Subjects with positive serology but negative hepatitis C virus (HCV) ribonucleic acid (RNA) test results are eligible. * Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to first dose of study treatment. * Subject has symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Subject with asymptomatic CNS metastases is eligible. * Subject has had a major surgical procedure and has not completely recovered within 28 days prior to the first dose of study treatment. * Subject has psychiatric illness or social situations that would preclude study compliance. * Subject has another malignancy for which treatment is required. Subject with negligible risk of metastasis or death is eligible (e.g., basal or squamous cell skin cancer, localized prostate cancer treated with curative intent or incidental prostate cancer T1-T2a, Gleeson ≤ 3 + 4, PSA ≤ 0.5 and who are undergoing active surveillance). * Subject has any concurrent disease, infection, or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) of ASP1650 | Up to 28 days | The RP2D was determined via dose limiting toxicity (DLT) assessment by dose evaluation committee (DEC). DLT was evaluated according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. |
| Percentage of Participants With Confirmed Objective Response by Modified RECIST v1.1 | From randomization until confirmed CR or confirmed PR, whichever occurred first (up to 26.57 weeks) | Confirmed objective response was defined as the confirmed completed response (CR) or confirmed partial response (PR), as confirmed by investigator based on modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Per modified RECIST v1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Both Alpha-Fetoprotein (AFP) and Beta Human Chorionic Gonadotropin (beta-HCG) values were below the ULN. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. No increase ≥ 50% in 2 samples at least 1 week apart compared to nadir values for both AFP and beta-HCG. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2 | From randomization until confirmed CR or confirmed PR whichever occurred first (up to 26.57 weeks) | DOR was defined as the time from the date of the first confirmed response CR or confirmed PR (whichever was first recorded) as confirmed by investigator based on modified RECIST 1.1 and RECIST v1.1 to the date of disease progression or date of censoring, whichever was earlier. If a participant had not progressed, participant was censored at the date of last disease assessment or at the date of first confirmed CR/PR if no post-baseline disease assessment was available. DOR (in days) was calculated as: (Date of documented progressive disease \[PD\], death, or censoring) minus (Date of the first CR/PR which was subsequently confirmed) +1. Duration of response was planned to summarized only for participants receiving dose level 2 in phase 2. |
| Progression-Free Survival (PFS) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2 | From the date of first dose until the date of disease progression, or until death due to any cause (up to 26.57 weeks) | PFS was defined as the time from the date of first dose until the date of disease progression, or until death due to any cause. If a participant had neither progressed nor died, the participant was censored at the date of last disease as confirmed by investigator based on modified RECIST v1.1 and RECIST v1.1. The distribution of PFS was planned to be summarized only for participants receiving dose level 2 using Kaplan-Meier methodology. Per modified RECIST v1.1 and RECIST v1.1, Progressive disease (PD): appearance of one or more new lesions or at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must be an absolute increase of at least 5 mm. Additionally per modified RECIST v1.1, PD was increase ≥ 50% in serum tumor markers AFP or beta-hCG in 2 samples at least 1 week apart compared to nadir values. |
| Number of Participants With Adverse Events (AEs) | From first dose of study drug up to 30 days after the last dose of study drug (up to 41.14 weeks) | An AE was defined as any untoward medical occurrence in a participant administered with an Investigational Product (IP) which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign including abnormal laboratory finding/test result or other safety assessment, symptom, or disease temporally associated with use of IP whether or not considered related to IP. A treatment-emergent adverse event (TEAE) was defined as an AE with onset at any time from first dosing until last scheduled procedure. AEs were considered serious (SAEs) if AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, birth defect, or required inpatient hospitalization or led to prolongation of hospitalization. |
| Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Baseline, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1 (Duration of each treatment cycle was 14 days) | Number of participants with shifts from baseline to post baseline in ECOG PS levels were reported. ECOG has 6 levels (0-5). Level 0 is fully active, able to carry on all pre-disease performance without restriction; Level 1 is restricted in physically strenuous activity but ambulatory ad able to carry out work of a light or sedentary nature, e.g. light house work, office work; Level 2 is ambulatory and capable of all self care but unable to carry out any work activities; up and about more than 50% of waking hours; Level 3 is capable of only limited self care; confined to bed or chair more than 50% of waking hours; Level 4 is completely disabled; cannot carry on any self care; totally confined to bed or chair); and Level 5 is dead. |
| Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1 (duration of each cycle was 14 days) | Blood was drawn for the measurement of serum βhCG at day 1 of every cycle (14 day cycle) to align with imaging assessment until the participant develops radiological disease progression per RECIST v1.1 evaluation or starts other systemic anticancer treatment. To evaluate the effect of ASP1650 on changes in serum βhCG, disease response was derived for participants with elevated serum tumor markers at baseline using CR, PR and SD. |
| Percentage of Participants With Confirmed Objective Response by RECIST v1.1 | From randomization until confirmed CR or confirmed PR, whichever occurred first (up to 26.57 weeks) | Confirmed objective response was defined as the confirmed CR or PR, as confirmed by investigator based on RECIST v1.1. Per RECIST v1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Pharmacokinetics (PK) of ASP1650 in Plasma: Area Under the Concentration-Time Curve Over 336 Hours (AUC336) | Dose Level 1 - CID1, C3D1: predose, 1.5 h after start of infusion, immediately after end of infusion, 0.5, 1.5, 3, 6, 24, 48, 72 h after end of infusion; Dose Level 2 - C1D1, C3D1: predose, immediately after end of infusion | AUC336 was derived from the Pharmacokinetic (PK) plasma samples collected. Duration of each cycle was 14 days. |
| Pharmacokinetics (PK) of ASP1650 in Plasma: Maximum Concentration (Cmax) | Dose Level 1-CID1, C3D1: predose, 1.5 h after start of infusion, immediately after end of infusion, 0.5, 1.5, 3, 6, 24, 48, 72 h after end of infusion; Dose Level 2-C1D1, C3D1: predose, immediately after end of infusion | Cmax was derived from the PK plasma samples collected. Duration of each cycle was 14 days. |
| Pharmacokinetics (PK) of ASP1650 in Plasma: Time to Maximum Concentration (Tmax) | Dose Level 1- CID1, C3D1: predose, 1.5 h after start of infusion, immediately after end of infusion, 0.5, 1.5, 3, 6, 24, 48, 72 h after end of infusion; Dose Level 2- C1D1, C3D1: predose, immediately after end of infusion | Tmax was derived from the PK plasma samples collected. Duration of each cycle was 14 days. |
| Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C2D1,C3D1,C4D1,C5D1,C6D1,C7D1,C8D1,C9D1,C10D1,C11D1,C12D1:predose,1.5 h post start of infusion, immediately post end of infusion,0.5,1.5,3,6,24,48,72 h post end of infusion for Dose Level 1, and predose, immediately post end of infusion for Dose Level 2 | Ctrough was derived from the PK plasma samples collected. Duration of each cycle was 14 days. |
| Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Baseline, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1 (duration of each cycle was 14 days) | Blood was drawn for the measurement of serum AFP at day 1 of every cycle (14 day cycle) to align with imaging assessment until the participant develops radiological disease progression per RECIST v1.1 evaluation or starts other systemic anticancer treatment. To evaluate the effect of ASP1650 on changes in serum AFP, disease response was derived for participants with elevated serum tumor markers at baseline using CR, PR and SD. |
| Percentage of Participants With Clinical Benefit by Modified RECIST v1.1 and RECIST v1.1 | From randomization until confirmed CR, confirmed PR, or durable SD whichever occurred first (up to 26.57 weeks) | Clinical benefit: defined as best overall response of confirmed CR, confirmed PR, or durable stable disease (SD) as confirmed by investigator based on modified RECIST v1.1 and RECIST v1.1. Per RECIST v1.1 and modified RECIST V1.1, CR: disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. PR:at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference smallest sum diameters while on study. Durable SD: SD maintained for at least 12 weeks. Additionally, per modified RECIST v1.1, CR also included AFP and beta-HCG values below ULN. PR also included no increase ≥ 50% in 2 samples at least 1 week apart compared to nadir values both for AFP and beta-HCG. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 3 sites in the United States.
Pre-assignment details
Adult male participants with incurable platinum refractory germ cell tumors for whom no standard of care treatment exists or who are ineligible to receive available standard of care treatment based on investigator's clinical judgment, who met all inclusion criteria and met none of the exclusion criteria were enrolled in this study. A total of 23 participants entered screening process and out of which 4 participants failed screened process.
Participants by arm
| Arm | Count |
|---|---|
| ASP1650, Dose Level 1 Participants received ASP1650, dose level 1 as intravenous infusion, Q2W starting on C1D1 for up to a maximum of 12 cycles, or until a study discontinuation criteria was met, whichever occurred earlier. Duration of each treatment cycle was 14 days. | 6 |
| ASP1650, Dose Level 2 Participants received ASP1650, dose level 2 as intravenous infusion, Q2W starting on C1D1 for up to a maximum of 12 cycles or until a study discontinuation criteria was met, whichever occurred earlier. Duration of each treatment cycle was 14 days. | 13 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Miscellaneous | 0 | 1 |
| Overall Study | Progressive Disease | 5 | 10 |
Baseline characteristics
| Characteristic | ASP1650, Dose Level 2 | Total | ASP1650, Dose Level 1 |
|---|---|---|---|
| Age, Continuous | 36.9 Years STANDARD_DEVIATION 12.2 | 37.2 Years STANDARD_DEVIATION 11.4 | 37.8 Years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 15 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 18 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 13 Participants | 19 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 6 | 5 / 13 |
| other Total, other adverse events | 5 / 6 | 10 / 13 |
| serious Total, serious adverse events | 3 / 6 | 7 / 13 |
Outcome results
Primary
Percentage of Participants With Confirmed Objective Response by Modified RECIST v1.1
Confirmed objective response was defined as the confirmed completed response (CR) or confirmed partial response (PR), as confirmed by investigator based on modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Per modified RECIST v1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Both Alpha-Fetoprotein (AFP) and Beta Human Chorionic Gonadotropin (beta-HCG) values were below the ULN. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. No increase ≥ 50% in 2 samples at least 1 week apart compared to nadir values for both AFP and beta-HCG.
Time frame: From randomization until confirmed CR or confirmed PR, whichever occurred first (up to 26.57 weeks)
Population: Full analysis set (FAS) population which included all enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASP1650 | Percentage of Participants With Confirmed Objective Response by Modified RECIST v1.1 | 0.0 Percentage of participants |
| ASP1650, Dose Level 2 | Percentage of Participants With Confirmed Objective Response by Modified RECIST v1.1 | 0.0 Percentage of participants |
Primary
Recommended Phase 2 Dose (RP2D) of ASP1650
The RP2D was determined via dose limiting toxicity (DLT) assessment by dose evaluation committee (DEC). DLT was evaluated according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Time frame: Up to 28 days
Population: SAF population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASP1650 | Recommended Phase 2 Dose (RP2D) of ASP1650 | 1500 Milligram per meter square (mg/m^2) |
Secondary
Change From Baseline in Serum Alpha-Fetoprotein (AFP)
Blood was drawn for the measurement of serum AFP at day 1 of every cycle (14 day cycle) to align with imaging assessment until the participant develops radiological disease progression per RECIST v1.1 evaluation or starts other systemic anticancer treatment. To evaluate the effect of ASP1650 on changes in serum AFP, disease response was derived for participants with elevated serum tumor markers at baseline using CR, PR and SD.
Time frame: Baseline, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1 (duration of each cycle was 14 days)
Population: FAS population with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ASP1650 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Baseline | 948.65 Microgram per liter (ug/L) | Standard Deviation 2065.59 |
| ASP1650 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C7D1 | 94.00 Microgram per liter (ug/L) | — |
| ASP1650 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C5D1 | -8.00 Microgram per liter (ug/L) | — |
| ASP1650 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C8D1 | 138.00 Microgram per liter (ug/L) | — |
| ASP1650 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C2D1 | -84.03 Microgram per liter (ug/L) | Standard Deviation 257.7 |
| ASP1650 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C9D1 | 98.00 Microgram per liter (ug/L) | — |
| ASP1650 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C3D1 | -8.00 Microgram per liter (ug/L) | Standard Deviation 11.31 |
| ASP1650 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C4D1 | 5.00 Microgram per liter (ug/L) | — |
| ASP1650 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C6D1 | 99.00 Microgram per liter (ug/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C9D1 | -27.00 Microgram per liter (ug/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C11D1 | -579.10 Microgram per liter (ug/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C5D1 | 762.00 Microgram per liter (ug/L) | Standard Deviation 1101.92 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C12D1 | -598.90 Microgram per liter (ug/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C2D1 | 2504.03 Microgram per liter (ug/L) | Standard Deviation 6139.95 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C3D1 | 5404.50 Microgram per liter (ug/L) | Standard Deviation 11064.94 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C4D1 | 2592.25 Microgram per liter (ug/L) | Standard Deviation 4354.92 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C10D1 | -454.00 Microgram per liter (ug/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Baseline | 7116.52 Microgram per liter (ug/L) | Standard Deviation 14580.47 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C6D1 | 1343.00 Microgram per liter (ug/L) | Standard Deviation 1650.39 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C7D1 | 118.00 Microgram per liter (ug/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Alpha-Fetoprotein (AFP) | Change at C8D1 | 99.00 Microgram per liter (ug/L) | — |
Secondary
Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG)
Blood was drawn for the measurement of serum βhCG at day 1 of every cycle (14 day cycle) to align with imaging assessment until the participant develops radiological disease progression per RECIST v1.1 evaluation or starts other systemic anticancer treatment. To evaluate the effect of ASP1650 on changes in serum βhCG, disease response was derived for participants with elevated serum tumor markers at baseline using CR, PR and SD.
Time frame: Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1 (duration of each cycle was 14 days)
Population: FAS population with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ASP1650 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C6D1 | 0.00 International unit per liter (IU/L) | — |
| ASP1650 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Baseline | 32641.67 International unit per liter (IU/L) | Standard Deviation 70670.15 |
| ASP1650 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C7D1 | 0.00 International unit per liter (IU/L) | — |
| ASP1650 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C3D1 | 105.50 International unit per liter (IU/L) | Standard Deviation 149.2 |
| ASP1650 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C8D1 | 0.00 International unit per liter (IU/L) | — |
| ASP1650 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C9D1 | 0.00 International unit per liter (IU/L) | — |
| ASP1650 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C4D1 | 0.00 International unit per liter (IU/L) | — |
| ASP1650 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C5D1 | 0.00 International unit per liter (IU/L) | — |
| ASP1650 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C2D1 | 13847.50 International unit per liter (IU/L) | Standard Deviation 28555.07 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C10D1 | -9.00 International unit per liter (IU/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C11D1 | 12.00 International unit per liter (IU/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C4D1 | -1.25 International unit per liter (IU/L) | Standard Deviation 2.5 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C12D1 | 85.00 International unit per liter (IU/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C8D1 | 2.00 International unit per liter (IU/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Baseline | 1198.00 International unit per liter (IU/L) | Standard Deviation 2293.97 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C2D1 | 2573.42 International unit per liter (IU/L) | Standard Deviation 4680.05 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C3D1 | -0.83 International unit per liter (IU/L) | Standard Deviation 2.04 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C5D1 | -2.00 International unit per liter (IU/L) | Standard Deviation 3.46 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C6D1 | -1.00 International unit per liter (IU/L) | Standard Deviation 1.41 |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C7D1 | 1.00 International unit per liter (IU/L) | — |
| ASP1650, Dose Level 2 | Change From Baseline in Serum Beta Human Chorionic Gonadotropin (βhCG) | Change at C9D1 | 3.00 International unit per liter (IU/L) | — |
Secondary
Duration of Response (DOR) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2
DOR was defined as the time from the date of the first confirmed response CR or confirmed PR (whichever was first recorded) as confirmed by investigator based on modified RECIST 1.1 and RECIST v1.1 to the date of disease progression or date of censoring, whichever was earlier. If a participant had not progressed, participant was censored at the date of last disease assessment or at the date of first confirmed CR/PR if no post-baseline disease assessment was available. DOR (in days) was calculated as: (Date of documented progressive disease \[PD\], death, or censoring) minus (Date of the first CR/PR which was subsequently confirmed) +1. Duration of response was planned to summarized only for participants receiving dose level 2 in phase 2.
Time frame: From randomization until confirmed CR or confirmed PR whichever occurred first (up to 26.57 weeks)
Population: DOR was not analyzed since no participants had confirmed response of CR or PR in the study.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Duration of Response (DOR) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2 | Modified RECIST V1.1 | — |
| Unknown | Duration of Response (DOR) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2 | RECIST V1.1 | — |
Secondary
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered with an Investigational Product (IP) which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign including abnormal laboratory finding/test result or other safety assessment, symptom, or disease temporally associated with use of IP whether or not considered related to IP. A treatment-emergent adverse event (TEAE) was defined as an AE with onset at any time from first dosing until last scheduled procedure. AEs were considered serious (SAEs) if AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, birth defect, or required inpatient hospitalization or led to prolongation of hospitalization.
Time frame: From first dose of study drug up to 30 days after the last dose of study drug (up to 41.14 weeks)
Population: SAF population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ASP1650 | Number of Participants With Adverse Events (AEs) | Drug-Related TEAEs | 2 Participants |
| ASP1650 | Number of Participants With Adverse Events (AEs) | Drug-Related TEAE Leading to Death | 0 Participants |
| ASP1650 | Number of Participants With Adverse Events (AEs) | Drug-Related Serious TEAE | 0 Participants |
| ASP1650 | Number of Participants With Adverse Events (AEs) | TEAE Leading to Withdrawal of Treatment | 1 Participants |
| ASP1650 | Number of Participants With Adverse Events (AEs) | Serious TEAEs | 3 Participants |
| ASP1650 | Number of Participants With Adverse Events (AEs) | Drug-Related TEAE Leading to Withdrawal of Treatment | 0 Participants |
| ASP1650 | Number of Participants With Adverse Events (AEs) | TEAE Leading to Death | 1 Participants |
| ASP1650 | Number of Participants With Adverse Events (AEs) | Death | 3 Participants |
| ASP1650 | Number of Participants With Adverse Events (AEs) | TEAE | 5 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Adverse Events (AEs) | Death | 5 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Adverse Events (AEs) | TEAE | 13 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Adverse Events (AEs) | Drug-Related TEAEs | 5 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Adverse Events (AEs) | Serious TEAEs | 7 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Adverse Events (AEs) | Drug-Related Serious TEAE | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Adverse Events (AEs) | TEAE Leading to Death | 3 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Adverse Events (AEs) | Drug-Related TEAE Leading to Death | 0 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Adverse Events (AEs) | TEAE Leading to Withdrawal of Treatment | 0 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Adverse Events (AEs) | Drug-Related TEAE Leading to Withdrawal of Treatment | 0 Participants |
Secondary
Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Number of participants with shifts from baseline to post baseline in ECOG PS levels were reported. ECOG has 6 levels (0-5). Level 0 is fully active, able to carry on all pre-disease performance without restriction; Level 1 is restricted in physically strenuous activity but ambulatory ad able to carry out work of a light or sedentary nature, e.g. light house work, office work; Level 2 is ambulatory and capable of all self care but unable to carry out any work activities; up and about more than 50% of waking hours; Level 3 is capable of only limited self care; confined to bed or chair more than 50% of waking hours; Level 4 is completely disabled; cannot carry on any self care; totally confined to bed or chair); and Level 5 is dead.
Time frame: Baseline, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1 (Duration of each treatment cycle was 14 days)
Population: SAF population with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C7D1) | 0 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 2 (baseline) to 1 (C2D1) | 0 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C2D1) | 3 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 1 (C2D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 0 (C2D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C2D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C3D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 1 (C3D1) | 0 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 0 (C3D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C3D1) | 0 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C4D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C4D1) | 0 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C5D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 0 (C5D1) | 0 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C6D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C6D1) | 0 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C7D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C8D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C8D1) | 0 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C9D1) | 1 Participants |
| ASP1650 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C9D1) | 0 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C11D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C9D1) | 0 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C2D1) | 2 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C4D1) | 3 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C12D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 0 (C3D1) | 0 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C3D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C6D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C6D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C7D1) | 0 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C7D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C10D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C4D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C2D1) | 8 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C8D1) | 0 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 1 (C2D1) | 0 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C5D1) | 2 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 0 (C2D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C9D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 2 (baseline) to 1 (C2D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 0 (C5D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 0 (C3D1) | 4 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 1 (baseline) to 1 (C8D1) | 1 Participants |
| ASP1650, Dose Level 2 | Number of Participants With Shifts From Baseline to Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) | ECOG PS : 0 (baseline) to 1 (C3D1) | 1 Participants |
Secondary
Percentage of Participants With Clinical Benefit by Modified RECIST v1.1 and RECIST v1.1
Clinical benefit: defined as best overall response of confirmed CR, confirmed PR, or durable stable disease (SD) as confirmed by investigator based on modified RECIST v1.1 and RECIST v1.1. Per RECIST v1.1 and modified RECIST V1.1, CR: disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. PR:at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference smallest sum diameters while on study. Durable SD: SD maintained for at least 12 weeks. Additionally, per modified RECIST v1.1, CR also included AFP and beta-HCG values below ULN. PR also included no increase ≥ 50% in 2 samples at least 1 week apart compared to nadir values both for AFP and beta-HCG.
Time frame: From randomization until confirmed CR, confirmed PR, or durable SD whichever occurred first (up to 26.57 weeks)
Population: FAS population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ASP1650 | Percentage of Participants With Clinical Benefit by Modified RECIST v1.1 and RECIST v1.1 | Modified RECIST v1.1 | 0.0 Percentage of participants |
| ASP1650 | Percentage of Participants With Clinical Benefit by Modified RECIST v1.1 and RECIST v1.1 | RECIST v1.1 | 0.0 Percentage of participants |
| ASP1650, Dose Level 2 | Percentage of Participants With Clinical Benefit by Modified RECIST v1.1 and RECIST v1.1 | Modified RECIST v1.1 | 7.7 Percentage of participants |
| ASP1650, Dose Level 2 | Percentage of Participants With Clinical Benefit by Modified RECIST v1.1 and RECIST v1.1 | RECIST v1.1 | 7.7 Percentage of participants |
Secondary
Percentage of Participants With Confirmed Objective Response by RECIST v1.1
Confirmed objective response was defined as the confirmed CR or PR, as confirmed by investigator based on RECIST v1.1. Per RECIST v1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization until confirmed CR or confirmed PR, whichever occurred first (up to 26.57 weeks)
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASP1650 | Percentage of Participants With Confirmed Objective Response by RECIST v1.1 | 0.0 Percentage of participants |
| ASP1650, Dose Level 2 | Percentage of Participants With Confirmed Objective Response by RECIST v1.1 | 0.0 Percentage of participants |
Secondary
Pharmacokinetics (PK) of ASP1650 in Plasma: Area Under the Concentration-Time Curve Over 336 Hours (AUC336)
AUC336 was derived from the Pharmacokinetic (PK) plasma samples collected. Duration of each cycle was 14 days.
Time frame: Dose Level 1 - CID1, C3D1: predose, 1.5 h after start of infusion, immediately after end of infusion, 0.5, 1.5, 3, 6, 24, 48, 72 h after end of infusion; Dose Level 2 - C1D1, C3D1: predose, immediately after end of infusion
Population: Pharmacokinetic analysis set (PKAS) population with available data at each time point. PKAS population included all enrolled participants who took at least 1 dose of ASP1650 and for whom at least 1 ASP1650 concentration measurement was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Area Under the Concentration-Time Curve Over 336 Hours (AUC336) | C1D1 | 73000 microgram*hour per milliliter (ug*h/mL) | Standard Deviation 25600 |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Area Under the Concentration-Time Curve Over 336 Hours (AUC336) | C3D1 | 156000 microgram*hour per milliliter (ug*h/mL) | — |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Area Under the Concentration-Time Curve Over 336 Hours (AUC336) | C1D1 | 112000 microgram*hour per milliliter (ug*h/mL) | Standard Deviation 28300 |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Area Under the Concentration-Time Curve Over 336 Hours (AUC336) | C3D1 | 137000 microgram*hour per milliliter (ug*h/mL) | Standard Deviation 14800 |
Secondary
Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough)
Ctrough was derived from the PK plasma samples collected. Duration of each cycle was 14 days.
Time frame: C2D1,C3D1,C4D1,C5D1,C6D1,C7D1,C8D1,C9D1,C10D1,C11D1,C12D1:predose,1.5 h post start of infusion, immediately post end of infusion,0.5,1.5,3,6,24,48,72 h post end of infusion for Dose Level 1, and predose, immediately post end of infusion for Dose Level 2
Population: PKAS population with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C5D1 | 343 ug/mL | — |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C8D1 | 329 ug/mL | — |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C4D1 | 290 ug/mL | — |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C9D1 | 318 ug/mL | — |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C6D1 | 306 ug/mL | — |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C3D1 | 238 ug/mL | — |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C7D1 | 317 ug/mL | — |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C2D1 | 74.55 ug/mL | Standard Deviation 62.79 |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C9D1 | 296 ug/mL | — |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C10D1 | 223 ug/mL | — |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C11D1 | 21.3 ug/mL | — |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C12D1 | 82.4 ug/mL | — |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C2D1 | 111.64 ug/mL | Standard Deviation 44.59 |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C3D1 | 163.6 ug/mL | Standard Deviation 39.16 |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C4D1 | 184.5 ug/mL | Standard Deviation 56.7 |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C5D1 | 186.33 ug/mL | Standard Deviation 39.55 |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C6D1 | 232.5 ug/mL | Standard Deviation 20.51 |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C7D1 | 225 ug/mL | — |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) | C8D1 | 200 ug/mL | — |
Secondary
Pharmacokinetics (PK) of ASP1650 in Plasma: Maximum Concentration (Cmax)
Cmax was derived from the PK plasma samples collected. Duration of each cycle was 14 days.
Time frame: Dose Level 1-CID1, C3D1: predose, 1.5 h after start of infusion, immediately after end of infusion, 0.5, 1.5, 3, 6, 24, 48, 72 h after end of infusion; Dose Level 2-C1D1, C3D1: predose, immediately after end of infusion
Population: PKAS population with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Maximum Concentration (Cmax) | C3D1 | 904 microgram per milliliter (ug/mL) | — |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Maximum Concentration (Cmax) | C1D1 | 757 microgram per milliliter (ug/mL) | Standard Deviation 245 |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Maximum Concentration (Cmax) | C1D1 | 1080 microgram per milliliter (ug/mL) | Standard Deviation 277 |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Maximum Concentration (Cmax) | C3D1 | 1300 microgram per milliliter (ug/mL) | Standard Deviation 227 |
Secondary
Pharmacokinetics (PK) of ASP1650 in Plasma: Time to Maximum Concentration (Tmax)
Tmax was derived from the PK plasma samples collected. Duration of each cycle was 14 days.
Time frame: Dose Level 1- CID1, C3D1: predose, 1.5 h after start of infusion, immediately after end of infusion, 0.5, 1.5, 3, 6, 24, 48, 72 h after end of infusion; Dose Level 2- C1D1, C3D1: predose, immediately after end of infusion
Population: PKAS analysis with available data at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Time to Maximum Concentration (Tmax) | C1D1 | 2.03 hour |
| ASP1650 | Pharmacokinetics (PK) of ASP1650 in Plasma: Time to Maximum Concentration (Tmax) | C3D1 | 3.38 hour |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Time to Maximum Concentration (Tmax) | C1D1 | 4.50 hour |
| ASP1650, Dose Level 2 | Pharmacokinetics (PK) of ASP1650 in Plasma: Time to Maximum Concentration (Tmax) | C3D1 | 3.50 hour |
Secondary
Progression-Free Survival (PFS) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2
PFS was defined as the time from the date of first dose until the date of disease progression, or until death due to any cause. If a participant had neither progressed nor died, the participant was censored at the date of last disease as confirmed by investigator based on modified RECIST v1.1 and RECIST v1.1. The distribution of PFS was planned to be summarized only for participants receiving dose level 2 using Kaplan-Meier methodology. Per modified RECIST v1.1 and RECIST v1.1, Progressive disease (PD): appearance of one or more new lesions or at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must be an absolute increase of at least 5 mm. Additionally per modified RECIST v1.1, PD was increase ≥ 50% in serum tumor markers AFP or beta-hCG in 2 samples at least 1 week apart compared to nadir values.
Time frame: From the date of first dose until the date of disease progression, or until death due to any cause (up to 26.57 weeks)
Population: FAS population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ASP1650 | Progression-Free Survival (PFS) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2 | Modified RECIST V1.1 | 1.18 Months |
| ASP1650 | Progression-Free Survival (PFS) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2 | RECIST V1.1 | 1.45 Months |