A Study of ASP1570 in Adults With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This study is for adults with advanced solid tumors. Their tumor has either grown outside of the area where it started or it has spread to other parts of the body. Their cancer gets worse after standard therapy or they are unable to have standard therapy.
This study will provide more information on a potential new treatment for people with advanced solid tumors, called ASP1570.
This study will be in 2 parts.
In Part 1, the best dose of ASP1570 to give to people with advanced solid tumors will be worked out. Different small groups of people with advanced solid tumors will take lower to higher doses of ASP1570. There are 8 different doses in total, with each group staying on the same dose. After taking the lowest dose, the first group will be checked for medical problems. The next group can only take the higher dose if the first group on the lowest dose had no major medical problems. This will continue in the same way for each group. This means each group will take the next highest dose of ASP1570 as long as the previous group did not have any major medical problems.
Each group will take tablets of ASP1570 either once or twice every day in a 21-day cycle. They will continue with more treatment cycles on the same dose unless they have major medical problems, their cancer gets worse or the study doctor decides that person should stop treatment.
In Part 2, different small groups of people with advanced solid tumors will take the best dose of ASP1570 worked out from Part 1. The dose will not go above the highest dose that people took in Part 1 without getting major medical problems. Some groups of people will have specific advanced tumors. These include tumors from metastatic melanoma or non-small cell lung cancer (NSCLC for short). Other groups will have solid tumors that showed a response in Part 1. Again, each group will take tablets of ASP1570 once every day in a 21-day cycle. They will continue with more treatment cycles unless they have major medical problems, their cancer gets worse or the study doctor decides that person should stop treatment.
After treatment, people in the study will visit their clinic 45 days after their last dose of ASP1570. Then, the study clinic will contact each person in the study at least every 12 weeks until the end of the study or if they decide to leave the study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ASP1570 Monotherapy Dose Escalation Participants will receive daily dose of ASP1570 in a 21-day cycle. |
Drug: ASP1570
Oral tablet
|
| Experimental: ASP1570 Monotherapy Dose Expansion - Metastatic Melanoma Participants who have metastatic melanoma will receive recommended Phase 2 dose (RP2D) of ASP1570 in a 21-day cycle. |
Drug: ASP1570
Oral tablet
|
| Experimental: ASP1570 Monotherapy Dose Expansion - Non-Small Cell Lung Carcinoma (NSCLC) Participants who have NSCLC will receive RP2D of ASP1570 daily in a 21-day cycle. |
Drug: ASP1570
Oral tablet
|
| Experimental: ASP1570 Monotherapy Dose Expansion - Response Triggered Tumor Participants who have response triggered tumor type will receive RP2D of ASP1570 daily or a dose level with confirmed response observed that has been cleared and deemed tolerable by the Dose Escalation Committee, in a 21-day cycle. |
Drug: ASP1570
Oral tablet
|
Outcome Measures
Primary Outcome Measures
- Incidence of Dose Limiting Toxicities (DLTs) for ASP1570 Single Agent [21 days]
A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness.
- Number of Participants with Adverse Events (AEs) [Up to 27 months]
Adverse events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a participant temporally associated with the use of study IP, whether or not considered related to the study IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study IP. This includes events related to the comparator and events related to the (study) procedures.
- Change from baseline to 45 days after End of Treatment (EOT) in laboratory values [Baseline and 45 days after EOT]
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade changes from baseline to highest post-baseline grade will be assessed.
- Number of participants with vital sign abnormalities and/or AEs [Up to 27 months]
Number of participants with potentially clinically significant vital sign values.
- Number of participants with electrocardiogram (ECG) abnormalities and/or AEs [Up to 24 months]
Number of participants with potentially clinically significant ECG values.
Secondary Outcome Measures
- Objective Response Rate (ORR) of ASP1570 per Immune Response Evaluation Criteria in Solid Tumors (iRECIST) [Up to 27 months]
ORR is defined as the proportion of participants for each dose level whose best overall response is rated as Complete Response (CR) or Partial Response (PR) per iRECIST.
- ORR of ASP1570 per Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) [Up to 27 months]
ORR is defined as the proportion of participants for each dose level whose best overall response is rated as Complete Response (CR) or Partial Response (PR) per RECIST 1.1.
- Duration of Response (DOR) of ASP1570 per iRECIST [Up to 27 months]
DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per iRECIST.
- Duration of Response (DOR) of ASP1570 per RECIST 1.1 [Up to 27 months]
DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per RECIST 1.1.
- Disease Control Rate (DCR) of ASP1570 per iRECIST [Up to 27 months]
DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or SD per iRECIST.
- Disease Control Rate (DCR) of ASP1570 per RECIST 1.1 [Up to 27 months]
DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or SD per RECIST 1.1.
- Pharmacokinetics of ASP1570 in plasma: Maximum Concentration (Cmax) [Up to 27 months]
Cmax will be recorded from the PK plasma samples collected.
- Pharmacokinetics of ASP1570 in plasma: Time of Maximum Concentration (tmax) [Up to 27 months]
tmax will be recorded from the PK plasma samples collected.
- Pharmacokinetics of ASP1570 in plasma: Area under the plasma concentration-time curve during a dosage interval (AUCtau) [Up to 27 months]
AUCtau will be recorded from the PK plasma samples collected.
- Pharmacokinetics of ASP1570 in plasma: Trough plasma concentration (Ctrough) [Up to 27 months]
Ctrough will be recorded from the PK plasma samples collected.
- Changes in tumor infiltration with CD4/CD8 cells [Up to 27 months]
Proportion of participants with changes in infiltration of CD4/CD8 cells.
- Level of proliferation of CD4/CD8/Ki67+ cells [Up to 27 months]
Proportion of participants with changes in level of proliferation of CD4/CD8/Ki67+ cells in the tumor microenvironment resulting from ASP1570.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participant has locally-advanced (unresectable) or metastatic solid tumor malignancy which is confirmed by available pathology records or current biopsy.
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Participant has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
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Participant that has progressed after receiving all standard approved therapies or is no longer eligible for standard therapy.
-
Participant has an Eastern Cooperative Oncology Group Performance Status of 0, 1, or
-
Participant's last dose of prior antineoplastic therapy, including any immunotherapy, was at least 21 days prior to the first dose of Investigational Product(IP). A participant with epidermal growth factor receptor (EGFR) or anaplastic lymphomas kinase (ALK) mutation-positive non small cell lung cancer (NSCLC) is allowed to remain on EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor therapy until 4 days prior to the first dose of IP.
-
Participants who have received radiotherapy must have completed this therapy (including stereotactic radiosurgery) at least 2 weeks prior to the first dose of IP.
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Participant's adverse events (excluding alopecia) from prior therapy have improved to grade 1 or baseline at least 14 days prior to the first dose of IP. Note: Participants with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy, or skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment are allowed.
-
Participant has adequate organ function prior to start of study treatment as indicated by the following laboratory values. If a participant has received a recent blood transfusion, the laboratory tests must be obtained >= 4 weeks after any blood transfusion: Absolute Neutrophil Count (ANC) >= 1500/µL; Platelets >= 100,000/µL; Hemoglobin >= 9 g/dL; Creatinine either (a) <= institutional Upper Limits of Normal (ULN) OR (b) Creatinine clearance >= 60 mL/min (calculated by Cockcroft-Gault equation); Total Bilirubin either (a) <= 1.5 x ULN or (b) Direct bilirubin <= ULN and total bilirubin < 3 x ULN (for participants with Gilbert's syndrome); aspartate aminotransferase (AST) [serum glutamic oxaloacetic transaminase (SGOT)] and alanine aminotransferase (ALT) [serum glutamic pyruvic transaminase (SGPT)] <= 2.5 x ULN without liver metastases (or <= 5 x ULN if liver metastases are present); serum potassium >= 3.4 mEq/L; serum magnesium >= 1.7 mg/dL; serum ionized calcium >= 4.7 mg/dL.
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Participant has activated partial thromboplastin time and international normalized ratio (INR) <= 1.5 x ULN and is not receiving anticoagulation.
-
Female participant is not pregnant and at least one of the following conditions apply:
-
Not a woman of childbearing potential (WOCBP)
-
WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 45 days after final IP administration.
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Female participant must agree not to breastfeed starting at screening and throughout the study period and for 45 days after final IP administration.
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Female participant must not donate ova starting at first dose of IP and throughout the study period and for 45 days after final IP administration.
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Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 45 days after final IP administration.
-
Male participant must not donate sperm during the treatment period and for 45 days after final IP administration.
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Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 45 days after final IP administration.
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Participant agrees not to participate in another interventional study while receiving study treatment in the present study.
Exclusion Criteria:
-
Participant has received investigational therapy (other than an investigational EGFR TKI in a participant with EGFR activating mutations or ALK inhibitor in a participant with an ALK mutation) within 21 days or 5 half-lives, whichever is shorter, prior to the first dose of IP.
-
Participant requires or has received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to the first dose of IP. Participants using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone and up to 10 mg prednisone) are allowed.
-
Participant has received and requires strong or moderate CYP2D6 inhibitors (e.g., bupropion, fluoxetine, paroxetine, duloxetine, abiraterone) during the study.
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Participant has symptomatic central nervous system (CNS) metastases or participant has evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). Participants 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 no longer than 2 weeks.
-
Participant has an active autoimmune disease. Participants with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy, or skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment are allowed.
-
Participant was discontinued from prior immunomodulatory therapy due to a grade >= 3 toxicity that was mechanistically related (e.g., immune related) to the agent.
-
Participant has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required for the purposes of this study unless mandated by local health authority.
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Participant has any of the following per screening serology test:
-
Hepatitis A virus (HAV) antibodies (immunoglobulin M [IgM])
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Positive hepatitis B surface antigen (HBsAg) or detectable hepatitis B DNA. Participants with negative HBsAg, positive hepatitis B core antibody (anti-HBc) and negative hepatitis B surface antibody (anti-HBs) are eligible if hepatitis B DNA is undetectable
-
Hepatitis C virus (HCV) antibodies unless HCV RNA is undetectable
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Participant has received a live vaccine against infectious diseases within 28 days prior to the first dose of IP.
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Participant has a history of drug-induced pneumonitis (interstitial lung disease [ILD]), currently has pneumonitis or a prior history of ILD or noninfectious pneumonitis requiring high-dose glucocorticoids whether resolved or not.
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Participant has an infection requiring systemic therapy within 14 days prior to the first dose of IP.
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Participant has received a prior allogenic bone marrow or solid organ transplant.
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Participant is expected to require another form of antineoplastic therapy while on study treatment.
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Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of study treatment or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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Participant has inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications).
-
Participant has a corrected QT interval (Single ECG) using Fridericia's formula (QTcF)
450 msec (for male and female participants) during screening. ECGs will be performed in triplicate during screening.
-
Participant has a prior malignancy, other than the current malignancy for which the participant is seeking treatment, active (i.e., requiring treatment or 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.
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Participant has had a major surgical procedure and has not completely recovered within 28 days prior to the first dose of IP.
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Participant has a history of bleeding diathesis.
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Participant requires use of any anticoagulation therapy.
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Participant has any condition which makes the participant unsuitable for study participation.
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Participant has a known or suspected hypersensitivity to ASP1570, or any components of the formulation used.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Providence Medical Foundation | Fullerton | California | United States | 92835 |
| 2 | Florida Cancer Specialist & Research Institute Sarasota | Sarasota | Florida | United States | 34232 |
| 3 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 4 | University of Kentucky Medical Center MCC-CRO | Lexington | Kentucky | United States | 40536 |
| 5 | Nebraska Methodist Hospital | Omaha | Nebraska | United States | 68130 |
| 6 | University Hospitals Cleveland Medical Center | Cleveland | Ohio | United States | 44106 |
| 7 | UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15232 |
| 8 | Tennessee Oncology | Nashville | Tennessee | United States | 37203 |
| 9 | Mary Crowley Research Center | Dallas | Texas | United States | 75230 |
Sponsors and Collaborators
- Astellas Pharma Global Development, Inc.
Investigators
- Study Director: Medical Director, Astellas Pharma Global Development, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1570-CL-0101