Clinical Trials List
Protocol NumberCMIW815X2102J
NCT Number(ClinicalTrials.gov Identfier)NCT03172936
2019-04-01 - 2020-01-02
Others
Terminated1
ICD-10C82.50
Diffuse follicle center lymphoma, unspecified site
ICD-10C82.59
Diffuse follicle center lymphoma, extranodal and solid organ sites
ICD-10C83.10
Mantle cell lymphoma, unspecified site
ICD-10C83.19
Mantle cell lymphoma, extranodal and solid organ sites
ICD-10C83.30
Diffuse large B-cell lymphoma, unspecified site
ICD-10C83.39
Diffuse large B-cell lymphoma, extranodal and solid organ sites
ICD-10C83.80
Other non-follicular lymphoma, unspecified site
ICD-10C83.89
Other non-follicular lymphoma, extranodal and solid organ sites
ICD-10C84.90
Mature T/NK-cell lymphomas, unspecified, unspecified site
ICD-10C84.99
Mature T/NK-cell lymphomas, unspecified, extranodal and solid organ sites
ICD-10C84.A0
Cutaneous T-cell lymphoma, unspecified, unspecified site
ICD-10C84.A9
Cutaneous T-cell lymphoma, unspecified, extranodal and solid organ sites
ICD-10C84.Z0
Other mature T/NK-cell lymphomas, unspecified site
ICD-10C84.Z9
Other mature T/NK-cell lymphomas, extranodal and solid organ sites
ICD-10C85.10
Unspecified B-cell lymphoma, unspecified site
ICD-10C85.19
Unspecified B-cell lymphoma, extranodal and solid organ sites
ICD-10C85.20
Mediastinal (thymic) large B-cell lymphoma, unspecified site
ICD-10C85.29
Mediastinal (thymic) large B-cell lymphoma, extranodal and solid organ sites
ICD-10C85.80
Other specified types of non-Hodgkin lymphoma, unspecified site
ICD-10C85.89
Other specified types of non-Hodgkin lymphoma, extranodal and solid organ sites
ICD-10C85.90
Non-Hodgkin lymphoma, unspecified, unspecified site
ICD-10C85.99
Non-Hodgkin lymphoma, unspecified, extranodal and solid organ sites
ICD-10C86.4
Blastic NK-cell lymphoma
ICD-10C88.4
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue [MALT-lymphoma]
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9202.80
Other lymphomas, unspecified, extranodal solid organ sites
A Phase Ib, Open Label, Multicenter Study of the Safety and Efficacy of MIW815 (ADU-S100) Administered by Intratumoral Injection With PDR001 to Patients With Advanced/Metastatic Solid Tumors or Lymphomas
-
Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chih-Hung Hsu Division of Hematology & Oncology
- MING YAO Division of General Internal Medicine
- Chiun Hsu Division of Hematology & Oncology
- Shang-Ju Wu Division of General Internal Medicine
- Ann-Lii Cheng Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳昭旭 Division of Dermatology
- Kun-Huei Yeh Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- YI-HUA LIAO Division of Dermatology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Advanced/Metastatic Solid Tumors or Lymphomas
Objectives
Primary Objectives
To characterize safety and tolerability of MIW815 (ADU-S100) given with PDR001 and identify recommended doses and schedule for future studies
Secondary Objectives
To evaluate the preliminary anti-tumor activity of the combination of MIW815 (ADU-S100) with PDR001
To characterize the PK of MIW815 (ADUS100) and PDR001
To assess the immunogenicity of PDR001
To assess Pharmacodynamic (PD) effects in injected and distal tumor lesions
Test Drug
MIW815 (ADU-S100) , PRD001
Active Ingredient
MIW815, PRD001
Dosage Form
MIW815: concentrate for solution for injection PRD001: powder for solution for infusion
Dosage
MIW815: 0.6 mg/0.6 mL, 4 mg/mL PRD001: 100 mg
Endpoints
Primary Outcome Measures :
Incidence of dose limiting toxicities (DLTs) [ Time Frame: 24 months ]
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with the combination of MIW815 (ADU-S100) and PDR001
Secondary Outcome Measures :
AUC inf [ Time Frame: 36 months ]
The area under the concentration-time curve extrapolated to infinity (mass*time/volume)
AUC last [ Time Frame: 36 months ]
The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume)
AUC tau [ Time Frame: 36 months ]
Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass* time/volume)
Tmax [ Time Frame: 36 months ]
The time to reach the maximum observed concentration (time)
Cmax [ Time Frame: 36 months ]
The maximum observed concentration (Cmax) following dose administration (mass/volume)
Lambda_z [ Time Frame: 36 months ]
Terminal elimination rate constant (1/time)
CL/F [ Time Frame: 36 months ]
Apparent systemic clearance of drug from the plasma (volume x time -1)
T1/2 [ Time Frame: 36 months ]
Elimination half-life, determined as 0.693/Lambda_z (time)
Vz/F [ Time Frame: 36 months ]
Apparent volume of distribution during the terminal elimination phase (volume)
Best overall response (BOR) [ Time Frame: 36 months ]
Best overall response will be summarized
Overall response rate (ORR) [ Time Frame: 36 months ]
Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI).
Progression free survival (PFS) [ Time Frame: 36 months ]
The survival function will be estimated using the Kaplan-Meier product limit method. Median duration, with a two-sided Brookmeyer-Crowley 90% confidence interval and Kaplan-Meier estimates of survival proportions will be provided at specified time points.
Disease control rate (DCR) [ Time Frame: 36 months ]
The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease
Time to response (TTR) [ Time Frame: 36 months ]
Time To Response is the time from first dose to first documented response (CR or PR). TTR will be summarized
Duration of Response (DOR) [ Time Frame: 36 months ]
Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due to study indication. Estimates will use Kaplan-Meier method
Tumor infiltrating lymphocytes (TIL) [ Time Frame: 36 months ]
Induction of TILs in the injected lesion (local PD effect) and in a non-injected lesion (distal PD effect) will be assessed using paired tumor samples at screening and on-treatment.
Incidence of dose limiting toxicities (DLTs) [ Time Frame: 24 months ]
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with the combination of MIW815 (ADU-S100) and PDR001
Secondary Outcome Measures :
AUC inf [ Time Frame: 36 months ]
The area under the concentration-time curve extrapolated to infinity (mass*time/volume)
AUC last [ Time Frame: 36 months ]
The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume)
AUC tau [ Time Frame: 36 months ]
Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass* time/volume)
Tmax [ Time Frame: 36 months ]
The time to reach the maximum observed concentration (time)
Cmax [ Time Frame: 36 months ]
The maximum observed concentration (Cmax) following dose administration (mass/volume)
Lambda_z [ Time Frame: 36 months ]
Terminal elimination rate constant (1/time)
CL/F [ Time Frame: 36 months ]
Apparent systemic clearance of drug from the plasma (volume x time -1)
T1/2 [ Time Frame: 36 months ]
Elimination half-life, determined as 0.693/Lambda_z (time)
Vz/F [ Time Frame: 36 months ]
Apparent volume of distribution during the terminal elimination phase (volume)
Best overall response (BOR) [ Time Frame: 36 months ]
Best overall response will be summarized
Overall response rate (ORR) [ Time Frame: 36 months ]
Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI).
Progression free survival (PFS) [ Time Frame: 36 months ]
The survival function will be estimated using the Kaplan-Meier product limit method. Median duration, with a two-sided Brookmeyer-Crowley 90% confidence interval and Kaplan-Meier estimates of survival proportions will be provided at specified time points.
Disease control rate (DCR) [ Time Frame: 36 months ]
The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease
Time to response (TTR) [ Time Frame: 36 months ]
Time To Response is the time from first dose to first documented response (CR or PR). TTR will be summarized
Duration of Response (DOR) [ Time Frame: 36 months ]
Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due to study indication. Estimates will use Kaplan-Meier method
Tumor infiltrating lymphocytes (TIL) [ Time Frame: 36 months ]
Induction of TILs in the injected lesion (local PD effect) and in a non-injected lesion (distal PD effect) will be assessed using paired tumor samples at screening and on-treatment.
Inclution Criteria
Inclusion criteria
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Written informed consent must be obtained prior to any procedures that are not part of
standard of care. For Japan only, written consent is necessary both from the patient and
his/her legal representative if he/she is under the age of 20 years.
2. Male or female ≥ 18 years.
3. Patients must have measurable disease as determined by RECIST v1.1 (for solid tumors)
or Cheson 2014 criteria (for lymphomas).
4. Patients must have at least two sites of disease amenable to biopsy and be a candidate for
tumor biopsy according to the treating institution’s guidelines. Patient must be willing to
undergo new tumor biopsies at screening and during therapy on the study according to the
treating institution’s own guidelines and requirements for such procedure. Exceptions may
be considered after documented discussions with Novartis.
Patients must have two lesions amenable to biopsy: one injected lesion must be 10
millimeters (mm) and <100 mm in longest diameter, and accessible for intratumoral
injection. For Group C, a visceral lesion amenable to intratumoral injection (using
ultrasound or CT guidance) is required.
The injected lesion must be an accessible cutaneous or subcutaneous lesion for
baseline and on-treatment biopsies.
The distal lesion must be accessible for baseline and on-treatment biopsy and must be
distinct from the injected lesion.
Tumors encasing major vascular structures such as the carotid artery or tumors in
locations that are at high risk for adverse events (i.e. pneumothorax), are not
considered appropriate for intratumoral injection.
5. Dose escalation/dose confirmation part of study: Patients with advanced/metastatic solid
tumors or lymphomas, who have progressed despite standard therapy or are intolerant to
standard therapy, for whom no standard therapy exists or for whom standard therapy is not
reasonably effective.
6. Dose expansion part of study: Melanoma patients with accessible cutaneous or
subcutaneous lesions, who have relapsed or progressed after responding to a PD-1 inhibitor
or who are refractory to PD-1 inhibitors. Dose expansion will also include patients with
accessible cutaneous or subcutaneous lesions with HNSCC or patients with other accessible
cutaneous or subcutaneous solid tumors and lymphomas, who have progressed despite
standard therapy or are intolerant of standard therapy, for whom no standard therapy exists
or for whom standard therapy is not reasonably effective. In addition, patients with
injectable visceral lesions who have MSS CRC or other solid tumors with accessible
visceral lesions, who have progressed despite standard therapy or are intolerant of standard
therapy, for whom no standard therapy exists or for whom standard therapy is not
reasonably effective.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Written informed consent must be obtained prior to any procedures that are not part of
standard of care. For Japan only, written consent is necessary both from the patient and
his/her legal representative if he/she is under the age of 20 years.
2. Male or female ≥ 18 years.
3. Patients must have measurable disease as determined by RECIST v1.1 (for solid tumors)
or Cheson 2014 criteria (for lymphomas).
4. Patients must have at least two sites of disease amenable to biopsy and be a candidate for
tumor biopsy according to the treating institution’s guidelines. Patient must be willing to
undergo new tumor biopsies at screening and during therapy on the study according to the
treating institution’s own guidelines and requirements for such procedure. Exceptions may
be considered after documented discussions with Novartis.
Patients must have two lesions amenable to biopsy: one injected lesion must be 10
millimeters (mm) and <100 mm in longest diameter, and accessible for intratumoral
injection. For Group C, a visceral lesion amenable to intratumoral injection (using
ultrasound or CT guidance) is required.
The injected lesion must be an accessible cutaneous or subcutaneous lesion for
baseline and on-treatment biopsies.
The distal lesion must be accessible for baseline and on-treatment biopsy and must be
distinct from the injected lesion.
Tumors encasing major vascular structures such as the carotid artery or tumors in
locations that are at high risk for adverse events (i.e. pneumothorax), are not
considered appropriate for intratumoral injection.
5. Dose escalation/dose confirmation part of study: Patients with advanced/metastatic solid
tumors or lymphomas, who have progressed despite standard therapy or are intolerant to
standard therapy, for whom no standard therapy exists or for whom standard therapy is not
reasonably effective.
6. Dose expansion part of study: Melanoma patients with accessible cutaneous or
subcutaneous lesions, who have relapsed or progressed after responding to a PD-1 inhibitor
or who are refractory to PD-1 inhibitors. Dose expansion will also include patients with
accessible cutaneous or subcutaneous lesions with HNSCC or patients with other accessible
cutaneous or subcutaneous solid tumors and lymphomas, who have progressed despite
standard therapy or are intolerant of standard therapy, for whom no standard therapy exists
or for whom standard therapy is not reasonably effective. In addition, patients with
injectable visceral lesions who have MSS CRC or other solid tumors with accessible
visceral lesions, who have progressed despite standard therapy or are intolerant of standard
therapy, for whom no standard therapy exists or for whom standard therapy is not
reasonably effective.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
Exclusion Criteria
1. Patients who require immediate local palliative measures such as XRT or surgery.
2. Symptomatic or untreated leptomeningeal disease.
3. Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that
require local CNS-directed therapy (such as XRT or surgery) or increasing doses of
corticosteroids within the prior 2 weeks. Patients with treated symptomatic brain metastases
should be neurologically stable (for 4 weeks post-treatment and prior to study entry) and off
of steroids for at least 2 weeks before administration of any study treatment.
4. History of severe hypersensitivity reactions to any ingredient of study drug(s) and other
monoclonal antibodies and/or their excipients.
5. Patients having out of range laboratory values defined as:
Creatinine > 1.5 x upper limit of normal (ULN)
Total bilirubin > 1.5 x ULN, except for patients with Gilbert’s syndrome who are
excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
Alanine aminotransferase (ALT) > 3 x ULN, except for patients that have tumor
involvement of the liver, who are excluded if ALT > 5 x ULN
Aspartate aminotransferase (AST) > 3 x ULN, except for patients that have tumor
involvement of the liver, who are excluded if AST > 5 x ULN
Absolute neutrophil count < 1.0 x 109
/L
Platelet count < 75 x 109
/L, except for patients in Group C escalation and expansion
where platelet count < 100 x 109
/L
INR > 1.5 x ULN and/or aPTT > 1.5 x ULN, except for patients in Group C
escalation and expansion where INR and aPTT must be normal
Hemoglobin (Hgb) < 9 grams/deciliter (g/dL)
Potassium, magnesium, calcium or phosphate abnormality > grade 1 using Common
Terminology Criteria for Adverse Events (CTCAE v4.03)
6. Impaired cardiac function or clinically significant cardiac disease, including any of the
following:
Clinically significant and/or uncontrolled heart disease such as congestive heart
failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or clinically
significant arrhythmia.
QTcF >470 msec on screening ECG or congenital long QT syndrome
Acute myocardial infarction or unstable angina pectoris < 3 months prior to study
entry
7. Known history of Human Immunodeficiency Virus (HIV) infection.
8. Active Epstein-Barr virus (EBV), HBV (hepatitis B virus) or HCV (hepatitis C virus).
9. Malignant disease, other than that being treated in this study. Exceptions to this exclusion:
malignancies that were treated curatively and have not recurred within 2 years prior to study
treatment; completely resected basal cell carcinoma and squamous cell carcinoma; and
completely resected carcinoma in situ of any type.
10. Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes,
residual hypothyroidism only requiring hormone replacement, psoriasis not requiring
systemic treatment or conditions not expected to recur, history of Hashimoto’s Thyroiditis
on stable dose of thyroid hormone replacement therapy may be considered. Patients
previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash
or with replacement therapy for endocrinopathies should not be excluded.
11. History of or current drug-induced interstitial lung disease or pneumonitis grade ≥2.
12. Patients who discontinued prior anti-PD-1 therapy due to an anti-PD-1-related toxicity.
13. Patients who required discontinuation of treatment due to treatment-related toxicities with
prior therapy directed against the same target as the drug(s) under study in this protocol.
14. Active infection requiring systemic antibiotic therapy.
15. Any medical condition that would, in the investigator’s judgment, prevent the patient’s
participation in the clinical study due to safety concerns, compliance with clinical study
procedures or interpretation of study results.
16. Treatment with cytotoxic or targeted antineoplastics within 4 weeks of initiation of study
treatment. For cytotoxic agents that have major delayed toxicities a washout period of one
cycle is indicated (examples are nitrosoureas and mitomycin C which typically require a 6
week washout). Prior antibodies or immunotherapies require a 4 week washout. Ongoing
bisphosphonate therapy and growth hormone-releasing hormone (GHRH) agonist therapy
is allowed.
17. Radiotherapy within 2 weeks of the first dose of study drug, except for palliative XRT to a
limited field, such as for the treatment of bone pain or a focally painful tumor mass. Prior
XRT to anatomical region of the injected and distal lesion is allowed provided the lesions
are either new or growing in size despite prior radiation and that the radiation was completed
at least 2 weeks before the first dose of study drug.
18. Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any
immunosuppressive therapy within 7 days of the first dose of study treatment. Topical
(
19. Patients receiving systemic treatment with any immunosuppressive medication.
20. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study
treatment.
21. Use of hematopoietic colony-stimulating growth factors [e.g. granulocyte colonystimulating factor (G-CSF), GM-CSF, macrophage colony-stimulating factor (M-CSF)],
thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior start of study
treatment. If thrombopoietin mimetics or erythroid stimulating agents were initiated more
than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose,
they can be maintained.
22. Participation in an interventional, investigational study within 4 weeks of the first dose of
study treatment.
23. Presence of ≥ CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and
ototoxicity which are excluded only if ≥ CTCAE grade 3) due to prior cancer therapy.
24. Major surgery within 2 weeks of the first dose of study treatment.
25. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female
after conception and until the termination of gestation, confirmed by a positive human
chorionic gonadotropin (hCG) laboratory test.
26. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception during
dosing and for 150 days after the last dose of study treatment. Highly effective
contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods)
and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking
study treatment. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). The vasectomized male partner
should be the sole partner for that subject.
Barrier methods of contraception: Condom or Occlusive cap. For the UK: with
spermicidal foam/gel/film/cream/ vaginal suppository
Use of oral, injected or implanted hormonal methods of contraception or placement of
an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal
contraception that have comparable efficacy (failure rate <1%), for example hormone
vaginal ring or transdermal hormone contraception.
In case of use of oral contraception women should have been stable on the same pill for a
minimum of 3 months before taking study treatment.
Women are considered post-menopausal and not of child bearing potential if they have had
over 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate [generally age from 40 to 59 years], history of vasomotor symptoms
[e.g. hot flush]) in the absence of other medical justification or have had surgical bilateral
oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least
six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the
woman has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential.
27. Sexually active males must use a condom during intercourse while taking the drug and for
30 days after stopping MIW815 (ADU-S100) and should not father a child in this period.
A condom is required to be used also by vasectomized men in order to prevent delivery of
the drug via seminal fluid.
2. Symptomatic or untreated leptomeningeal disease.
3. Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that
require local CNS-directed therapy (such as XRT or surgery) or increasing doses of
corticosteroids within the prior 2 weeks. Patients with treated symptomatic brain metastases
should be neurologically stable (for 4 weeks post-treatment and prior to study entry) and off
of steroids for at least 2 weeks before administration of any study treatment.
4. History of severe hypersensitivity reactions to any ingredient of study drug(s) and other
monoclonal antibodies and/or their excipients.
5. Patients having out of range laboratory values defined as:
Creatinine > 1.5 x upper limit of normal (ULN)
Total bilirubin > 1.5 x ULN, except for patients with Gilbert’s syndrome who are
excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
Alanine aminotransferase (ALT) > 3 x ULN, except for patients that have tumor
involvement of the liver, who are excluded if ALT > 5 x ULN
Aspartate aminotransferase (AST) > 3 x ULN, except for patients that have tumor
involvement of the liver, who are excluded if AST > 5 x ULN
Absolute neutrophil count < 1.0 x 109
/L
Platelet count < 75 x 109
/L, except for patients in Group C escalation and expansion
where platelet count < 100 x 109
/L
INR > 1.5 x ULN and/or aPTT > 1.5 x ULN, except for patients in Group C
escalation and expansion where INR and aPTT must be normal
Hemoglobin (Hgb) < 9 grams/deciliter (g/dL)
Potassium, magnesium, calcium or phosphate abnormality > grade 1 using Common
Terminology Criteria for Adverse Events (CTCAE v4.03)
6. Impaired cardiac function or clinically significant cardiac disease, including any of the
following:
Clinically significant and/or uncontrolled heart disease such as congestive heart
failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or clinically
significant arrhythmia.
QTcF >470 msec on screening ECG or congenital long QT syndrome
Acute myocardial infarction or unstable angina pectoris < 3 months prior to study
entry
7. Known history of Human Immunodeficiency Virus (HIV) infection.
8. Active Epstein-Barr virus (EBV), HBV (hepatitis B virus) or HCV (hepatitis C virus).
9. Malignant disease, other than that being treated in this study. Exceptions to this exclusion:
malignancies that were treated curatively and have not recurred within 2 years prior to study
treatment; completely resected basal cell carcinoma and squamous cell carcinoma; and
completely resected carcinoma in situ of any type.
10. Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes,
residual hypothyroidism only requiring hormone replacement, psoriasis not requiring
systemic treatment or conditions not expected to recur, history of Hashimoto’s Thyroiditis
on stable dose of thyroid hormone replacement therapy may be considered. Patients
previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash
or with replacement therapy for endocrinopathies should not be excluded.
11. History of or current drug-induced interstitial lung disease or pneumonitis grade ≥2.
12. Patients who discontinued prior anti-PD-1 therapy due to an anti-PD-1-related toxicity.
13. Patients who required discontinuation of treatment due to treatment-related toxicities with
prior therapy directed against the same target as the drug(s) under study in this protocol.
14. Active infection requiring systemic antibiotic therapy.
15. Any medical condition that would, in the investigator’s judgment, prevent the patient’s
participation in the clinical study due to safety concerns, compliance with clinical study
procedures or interpretation of study results.
16. Treatment with cytotoxic or targeted antineoplastics within 4 weeks of initiation of study
treatment. For cytotoxic agents that have major delayed toxicities a washout period of one
cycle is indicated (examples are nitrosoureas and mitomycin C which typically require a 6
week washout). Prior antibodies or immunotherapies require a 4 week washout. Ongoing
bisphosphonate therapy and growth hormone-releasing hormone (GHRH) agonist therapy
is allowed.
17. Radiotherapy within 2 weeks of the first dose of study drug, except for palliative XRT to a
limited field, such as for the treatment of bone pain or a focally painful tumor mass. Prior
XRT to anatomical region of the injected and distal lesion is allowed provided the lesions
are either new or growing in size despite prior radiation and that the radiation was completed
at least 2 weeks before the first dose of study drug.
18. Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any
immunosuppressive therapy within 7 days of the first dose of study treatment. Topical
(
19. Patients receiving systemic treatment with any immunosuppressive medication.
20. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study
treatment.
21. Use of hematopoietic colony-stimulating growth factors [e.g. granulocyte colonystimulating factor (G-CSF), GM-CSF, macrophage colony-stimulating factor (M-CSF)],
thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior start of study
treatment. If thrombopoietin mimetics or erythroid stimulating agents were initiated more
than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose,
they can be maintained.
22. Participation in an interventional, investigational study within 4 weeks of the first dose of
study treatment.
23. Presence of ≥ CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and
ototoxicity which are excluded only if ≥ CTCAE grade 3) due to prior cancer therapy.
24. Major surgery within 2 weeks of the first dose of study treatment.
25. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female
after conception and until the termination of gestation, confirmed by a positive human
chorionic gonadotropin (hCG) laboratory test.
26. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception during
dosing and for 150 days after the last dose of study treatment. Highly effective
contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods)
and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking
study treatment. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). The vasectomized male partner
should be the sole partner for that subject.
Barrier methods of contraception: Condom or Occlusive cap. For the UK: with
spermicidal foam/gel/film/cream/ vaginal suppository
Use of oral, injected or implanted hormonal methods of contraception or placement of
an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal
contraception that have comparable efficacy (failure rate <1%), for example hormone
vaginal ring or transdermal hormone contraception.
In case of use of oral contraception women should have been stable on the same pill for a
minimum of 3 months before taking study treatment.
Women are considered post-menopausal and not of child bearing potential if they have had
over 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate [generally age from 40 to 59 years], history of vasomotor symptoms
[e.g. hot flush]) in the absence of other medical justification or have had surgical bilateral
oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least
six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the
woman has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential.
27. Sexually active males must use a condom during intercourse while taking the drug and for
30 days after stopping MIW815 (ADU-S100) and should not father a child in this period.
A condom is required to be used also by vasectomized men in order to prevent delivery of
the drug via seminal fluid.
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
140 participants
