Clinical Trials List
Protocol Number8374-CL-0101
NCT Number(ClinicalTrials.gov Identfier)NCT03260322
2018-12-18 - 2021-12-31
Phase I
Recruiting3
ICD-9199.0
Disseminated malignant neoplasm
A Phase 1b Study of ASP8374, an Immune Checkpoint Inhibitor, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
-
Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
-
Sponsor
Astellas Pharma Global Development Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
- Li-Yuan Bai Division of Hematology & Oncology
- Tao-Wei Ke Division of Colorectal Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Sin-Syue Li Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
- Nai-Jung Chiang Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- 姜乃榕 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- 徐偉勛 醫學研究部
- 廖斌志 Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
- James Chih-Hsin Yang Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Advanced Solid Tumors
Objectives
Primary Objectives:
To evaluate the tolerability and safety profile of ASP8374 in subjects with locally advanced
(unresectable) or metastatic solid tumors.
To characterize the pharmacokinetic profile of ASP8374.
To determine the recommended Phase 2 dose (RP2D) of ASP8374.
Secondary Objective:
To evaluate the anti-tumor effect of ASP8374.
Exploratory Objectives:
To evaluate the immunogenicity of ASP8374.
To evaluate target engagement of ASP8374.
To evaluate pharmacodynamic activities of ASP8374.
To investigate biomarkers that may correlate with treatment outcome of ASP8374.
To evaluate progression-free survival (PFS) of subjects with selected tumor types who are treated
with ASP8374.
Test Drug
ASP8374(PTZ-201)
Active Ingredient
ASP8374
Dosage Form
injection
Dosage
20
Endpoints
Primary
Safety and tolerability as noted by: DLTs, AEs, immune-related AEs (irAEs), serious AEs
(SAEs), laboratory test results (Complete blood count [CBC], serum chemistry, urinalysis,
pregnancy test, thyroid stimulating hormone [TSH] and free T4), electrocardiograms (ECGs),
vital signs, physical exams and ECOG performance status.
Pharmacokinetics parameters (AUClast, AUCinf, AUCtau, Cmax, Ctrough, Tmax, t1/2, CL, V as
applicable) of ASP8374.
Secondary:
Objective response rate (ORR), duration of response (DOR), persistence of response after
discontinuation, and disease control rate (DCR) by RECIST 1.1 and iRECIST.
Exploratory:
Immunogenicity of ASP8374 as measured by the frequency of anti-drug antibody (ADA) positive
subjects.
Determination of ASP8374 target engagement by analysis of receptor occupancy on peripheral
blood cells in subjects treated with the ASP8374.
Pharmacodynamic effects of ASP8374.
Biomarkers that may correlate with treatment outcome of ASP8374.
Progression-free survival (PFS).
Safety and tolerability as noted by: DLTs, AEs, immune-related AEs (irAEs), serious AEs
(SAEs), laboratory test results (Complete blood count [CBC], serum chemistry, urinalysis,
pregnancy test, thyroid stimulating hormone [TSH] and free T4), electrocardiograms (ECGs),
vital signs, physical exams and ECOG performance status.
Pharmacokinetics parameters (AUClast, AUCinf, AUCtau, Cmax, Ctrough, Tmax, t1/2, CL, V as
applicable) of ASP8374.
Secondary:
Objective response rate (ORR), duration of response (DOR), persistence of response after
discontinuation, and disease control rate (DCR) by RECIST 1.1 and iRECIST.
Exploratory:
Immunogenicity of ASP8374 as measured by the frequency of anti-drug antibody (ADA) positive
subjects.
Determination of ASP8374 target engagement by analysis of receptor occupancy on peripheral
blood cells in subjects treated with the ASP8374.
Pharmacodynamic effects of ASP8374.
Biomarkers that may correlate with treatment outcome of ASP8374.
Progression-free survival (PFS).
Inclution Criteria
Inclusion:
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written
informed consent and privacy language as per national regulations (e.g., HIPAA Authorization for
U.S. sites) must be obtained from the subject or legally authorized representative prior to any
study-related procedures (including withdrawal of prohibited medication, if applicable).
2. The subject is at least 18 years of age and legally an adult according to local regulation at the time
of signing informed consent.
3. Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the
number of prior treatment regimens) that is confirmed by available pathology records or current
biopsy as well as:
a) Subject in the escalation cohort has received all standard therapies (unless the therapy is
contraindicated or intolerable) felt to provide clinical benefit in the opinion of the treating
investigator for his/her specific tumor type.
OR
b) Subject in an expansion cohort has received at least one standard therapy for his/her specific
tumor type.
4. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
5. Subject’s last dose of prior antineoplastic therapy, including any immunotherapy, was at least
21 days prior to initiation of study drug administration. A subject with epidermal growth factor
receptor (EGFR) mutation-positive NSCLC is allowed to remain on EGFR tyrosine kinase
inhibitor (TKI) therapy until 4 days prior to the start of study drug administration.
6. Subject has completed any radiotherapy (including stereotactic radiosurgery) at least 2 weeks
prior to study drug administration.
7. Subject’s adverse events (excluding alopecia) from prior therapy have improved to grade 1 or
baseline prior to start of study treatment.
8. Subject with mCRPC (positive bone scan and/or soft tissue disease documented by CT/MRI)
meets both of the following:
Subject has serum testosterone ≤ 50 ng/dL at screening.
Subject has had an orchiectomy or plans to continue androgen deprivation therapy (ADT)
for the duration of study treatment
9. Subject has adequate organ function within 7 days prior to start of study treatment as indicated by
the following laboratory values. If a subject has received a recent blood transfusion, the laboratory
tests must be obtained ≥ 4 weeks after any blood transfusion:
10. Female subject must either:
Be of non-childbearing potential:
Postmenopausal (defined as at least 1 year without any menses for which there is no
other obvious pathological or physiological cause) prior to screening, or
Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral
oophorectomy).
Or, if of childbearing potential,
Agree not to try to become pregnant during the study treatment and for 6 months after
the final study drug administration.
And have a negative urine or serum pregnancy test prior to study drug administration.
And, if heterosexually active, agree to consistently use one form of highly effective
birth control* starting at screening and throughout the study treatment and 6 months
after the final study drug administration.
*Highly effective forms of birth control include:
Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
Established intrauterine device (IUD) or intrauterine system (IUS)
Bilateral tubal occlusion
Vasectomy (A vasectomy is a highly effective contraception method provided the absence
of sperm has been confirmed. If not, an additional highly effective method of contraception
should be used)
Male is sterile due to a bilateral orchiectomy
Sexual abstinence is considered a highly effective method only if defined as refraining from
heterosexual activity during the entire period of risk associated with the study drug. The
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study
and the preferred and usual lifestyle of the participant.
11. Female subject must agree not to breastfeed starting at screening and throughout the study
treatment, and for 6 months after the final study drug administration.
12. Female subject must not donate ova starting at screening and throughout the study treatment, and
for 6 months after the final study drug administration.
13. A sexually active male subject with female partner(s) who are of childbearing potential is eligible
if:
Agree to use a male condom starting at screening and continue throughout the study
treatment, and for 6 months after the final study drug administration.
If the male subject has not had a vasectomy or is not sterile as defined below their female
partner(s) is utilizing one form of highly effective birth control* starting at screening and
continue throughout the study treatment and for 6 months after the final study drug
administration.
14. Male subject must not donate sperm starting at screening and throughout the study treatment, and
for 6 months after the final study drug administration.
15. 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
treatment and for 6 months after the final study drug administration.
16. Subject agrees not to participate in another interventional study while receiving study drug
(subjects who are currently in the follow-up period of an interventional clinical trial are allowed).
Additional Inclusion Criteria for Subjects in the Expansion Cohorts:
17. Subject meets one of the following:
Subject has the tumor type for which a confirmed response was observed in a monotherapy
dose escalation cohort; or
For an expansion cohort opened due to achieving predicted efficacious exposure, subject has
SCCHN.
18. Subject has at least 1 measureable lesion per RECIST 1.1. The measureable lesion must be
outside the field of radiation if subject had prior radiotherapy. Subjects with mCRPC who do not
have measurable lesions must have at least one of the following:
Progression with 2 or more new bone lesions; or
Prostate-specific antigen (PSA) progression (defined as a minimum of three rising PSA
levels with an interval of ≥ 1 week between each determination) within 6 weeks prior to
study drug administration and a PSA value at the screening visit ≥ 2 ng/mL.
19. Subject has an available tumor specimen in a tissue block or unstained serial slides obtained
within 56 days prior to first dose of study treatment, or subject is an appropriate candidate for
tumor biopsy and is amenable to undergoing a tumor biopsy (core needle biopsy or excision)
during the screening period.
20. Subject in a SCCHN monotherapy expansion cohort, is an appropriate candidate for tumor biopsy
and consents to undergoing a tumor biopsy (core needle biopsy or excision) during the treatment
period as indicated in the Schedule of Assessments.
Waivers to the inclusion criteria will NOT be allowed.
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written
informed consent and privacy language as per national regulations (e.g., HIPAA Authorization for
U.S. sites) must be obtained from the subject or legally authorized representative prior to any
study-related procedures (including withdrawal of prohibited medication, if applicable).
2. The subject is at least 18 years of age and legally an adult according to local regulation at the time
of signing informed consent.
3. Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the
number of prior treatment regimens) that is confirmed by available pathology records or current
biopsy as well as:
a) Subject in the escalation cohort has received all standard therapies (unless the therapy is
contraindicated or intolerable) felt to provide clinical benefit in the opinion of the treating
investigator for his/her specific tumor type.
OR
b) Subject in an expansion cohort has received at least one standard therapy for his/her specific
tumor type.
4. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
5. Subject’s last dose of prior antineoplastic therapy, including any immunotherapy, was at least
21 days prior to initiation of study drug administration. A subject with epidermal growth factor
receptor (EGFR) mutation-positive NSCLC is allowed to remain on EGFR tyrosine kinase
inhibitor (TKI) therapy until 4 days prior to the start of study drug administration.
6. Subject has completed any radiotherapy (including stereotactic radiosurgery) at least 2 weeks
prior to study drug administration.
7. Subject’s adverse events (excluding alopecia) from prior therapy have improved to grade 1 or
baseline prior to start of study treatment.
8. Subject with mCRPC (positive bone scan and/or soft tissue disease documented by CT/MRI)
meets both of the following:
Subject has serum testosterone ≤ 50 ng/dL at screening.
Subject has had an orchiectomy or plans to continue androgen deprivation therapy (ADT)
for the duration of study treatment
9. Subject has adequate organ function within 7 days prior to start of study treatment as indicated by
the following laboratory values. If a subject has received a recent blood transfusion, the laboratory
tests must be obtained ≥ 4 weeks after any blood transfusion:
10. Female subject must either:
Be of non-childbearing potential:
Postmenopausal (defined as at least 1 year without any menses for which there is no
other obvious pathological or physiological cause) prior to screening, or
Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral
oophorectomy).
Or, if of childbearing potential,
Agree not to try to become pregnant during the study treatment and for 6 months after
the final study drug administration.
And have a negative urine or serum pregnancy test prior to study drug administration.
And, if heterosexually active, agree to consistently use one form of highly effective
birth control* starting at screening and throughout the study treatment and 6 months
after the final study drug administration.
*Highly effective forms of birth control include:
Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
Established intrauterine device (IUD) or intrauterine system (IUS)
Bilateral tubal occlusion
Vasectomy (A vasectomy is a highly effective contraception method provided the absence
of sperm has been confirmed. If not, an additional highly effective method of contraception
should be used)
Male is sterile due to a bilateral orchiectomy
Sexual abstinence is considered a highly effective method only if defined as refraining from
heterosexual activity during the entire period of risk associated with the study drug. The
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study
and the preferred and usual lifestyle of the participant.
11. Female subject must agree not to breastfeed starting at screening and throughout the study
treatment, and for 6 months after the final study drug administration.
12. Female subject must not donate ova starting at screening and throughout the study treatment, and
for 6 months after the final study drug administration.
13. A sexually active male subject with female partner(s) who are of childbearing potential is eligible
if:
Agree to use a male condom starting at screening and continue throughout the study
treatment, and for 6 months after the final study drug administration.
If the male subject has not had a vasectomy or is not sterile as defined below their female
partner(s) is utilizing one form of highly effective birth control* starting at screening and
continue throughout the study treatment and for 6 months after the final study drug
administration.
14. Male subject must not donate sperm starting at screening and throughout the study treatment, and
for 6 months after the final study drug administration.
15. 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
treatment and for 6 months after the final study drug administration.
16. Subject agrees not to participate in another interventional study while receiving study drug
(subjects who are currently in the follow-up period of an interventional clinical trial are allowed).
Additional Inclusion Criteria for Subjects in the Expansion Cohorts:
17. Subject meets one of the following:
Subject has the tumor type for which a confirmed response was observed in a monotherapy
dose escalation cohort; or
For an expansion cohort opened due to achieving predicted efficacious exposure, subject has
SCCHN.
18. Subject has at least 1 measureable lesion per RECIST 1.1. The measureable lesion must be
outside the field of radiation if subject had prior radiotherapy. Subjects with mCRPC who do not
have measurable lesions must have at least one of the following:
Progression with 2 or more new bone lesions; or
Prostate-specific antigen (PSA) progression (defined as a minimum of three rising PSA
levels with an interval of ≥ 1 week between each determination) within 6 weeks prior to
study drug administration and a PSA value at the screening visit ≥ 2 ng/mL.
19. Subject has an available tumor specimen in a tissue block or unstained serial slides obtained
within 56 days prior to first dose of study treatment, or subject is an appropriate candidate for
tumor biopsy and is amenable to undergoing a tumor biopsy (core needle biopsy or excision)
during the screening period.
20. Subject in a SCCHN monotherapy expansion cohort, is an appropriate candidate for tumor biopsy
and consents to undergoing a tumor biopsy (core needle biopsy or excision) during the treatment
period as indicated in the Schedule of Assessments.
Waivers to the inclusion criteria will NOT be allowed.
Exclusion Criteria
Exclusion:
1. Subject weighs < 45 kg at screening.
2. Subject has received investigational therapy (other than an investigational EGFR TKI in a subject
with EGFR activating mutations) within 21 days prior to start of study drug.
3. Subject requires or has received systemic steroid therapy or any other immunosuppressive therapy
within 14 days prior to study drug administration. Subjects using a physiologic replacement dose
of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone up to 10 mg
per day of prednisone) are allowed.
4. Subject has symptomatic central nervous system (CNS) metastases or subject has evidence of
unstable CNS metastases even if asymptomatic (e.g., progression on scans). Subjects with
previously treated 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.
5. Subject has an active autoimmune disease. Subjects 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.
6. Subject was discontinued from prior immunomodulatory therapy due to a grade ≥ 3 toxicity that
was mechanistically related (e.g., immune related) to the agent in the judgment of the investigator.
7. Subject has known history of serious hypersensitivity reaction to a known ingredient of ASP8374
or severe hypersensitivity reaction to treatment with another monoclonal antibody.
8. Subject has a known history of Human Immunodeficiency Virus.
9. Subject is positive for Hepatitis B (HbsAg reactive) or Hepatitis C ([HCV]; ribonucleic acid
[RNA] detected by qualitative assay). Hepatitis C RNA testing is not required in subjects with
negative Hepatitis C antibody testing.
10. Subject has received a live vaccine against infectious diseases within 28 days prior to initiation of
study treatment.
11. Subject has a history of drug-induced pneumonitis (interstitial lung disease) or currently has
pneumonitis.
12. Subject has an infection requiring systemic therapy.
13. Subject has received a prior allogeneic bone marrow or solid organ transplant.
14. Subject is expected to require another form of antineoplastic therapy while on study treatment.
15. Subject 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.
16. Any condition that, in the investigator’s opinion, makes the subject unsuitable for study
participation.
Additional Exclusion Criteria for Subjects in Expansion Cohorts:
17. Subject has a prior malignancy active (i.e. requiring treatment of intervention) within the previous
2 years 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.
18. Subject has received prior treatment with a TIGIT inhibitor.
1. Subject weighs < 45 kg at screening.
2. Subject has received investigational therapy (other than an investigational EGFR TKI in a subject
with EGFR activating mutations) within 21 days prior to start of study drug.
3. Subject requires or has received systemic steroid therapy or any other immunosuppressive therapy
within 14 days prior to study drug administration. Subjects using a physiologic replacement dose
of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone up to 10 mg
per day of prednisone) are allowed.
4. Subject has symptomatic central nervous system (CNS) metastases or subject has evidence of
unstable CNS metastases even if asymptomatic (e.g., progression on scans). Subjects with
previously treated 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.
5. Subject has an active autoimmune disease. Subjects 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.
6. Subject was discontinued from prior immunomodulatory therapy due to a grade ≥ 3 toxicity that
was mechanistically related (e.g., immune related) to the agent in the judgment of the investigator.
7. Subject has known history of serious hypersensitivity reaction to a known ingredient of ASP8374
or severe hypersensitivity reaction to treatment with another monoclonal antibody.
8. Subject has a known history of Human Immunodeficiency Virus.
9. Subject is positive for Hepatitis B (HbsAg reactive) or Hepatitis C ([HCV]; ribonucleic acid
[RNA] detected by qualitative assay). Hepatitis C RNA testing is not required in subjects with
negative Hepatitis C antibody testing.
10. Subject has received a live vaccine against infectious diseases within 28 days prior to initiation of
study treatment.
11. Subject has a history of drug-induced pneumonitis (interstitial lung disease) or currently has
pneumonitis.
12. Subject has an infection requiring systemic therapy.
13. Subject has received a prior allogeneic bone marrow or solid organ transplant.
14. Subject is expected to require another form of antineoplastic therapy while on study treatment.
15. Subject 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.
16. Any condition that, in the investigator’s opinion, makes the subject unsuitable for study
participation.
Additional Exclusion Criteria for Subjects in Expansion Cohorts:
17. Subject has a prior malignancy active (i.e. requiring treatment of intervention) within the previous
2 years 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.
18. Subject has received prior treatment with a TIGIT inhibitor.
The Estimated Number of Participants
-
Taiwan
11 participants
-
Global
300 participants
