Study of WM-A1-3389 in Participants With Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
The purpose of the present study is to determine the safety, tolerability, and efficacy of WM-A1-3389 in combination with pembrolizumab in participants with advanced or metastatic solid tumors and non-small cell lung cancer (NSCLC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose escalation (Stage 1) WM-A1-3389 administered intravenously, weekly for 21 days of each cycle |
Biological: WM-A1-3389
Anti-IGSF1 (Immunoglobulin superfamily member 1)
|
| Experimental: Dose escalation (Stage 2) WM-A1-3389 administered intravenously, weekly for 21 days of each cycle Pembrolizumab 200 mg administered intravenously, every 3 weeks for 21 days of each cycle |
Biological: WM-A1-3389
Anti-IGSF1 (Immunoglobulin superfamily member 1)
Biological: Pembrolizumab
Anti-PD-1(Programmed cell death protein 1)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of Dose Limit Toxicities (DLT) [At the end of Cycle 1 (each cycle is 21 days)]
- Number of Participants Who Experienced an Adverse Event (AE) [Up to 6 Cycles (18 weeks)]
- Frequency of dose discontinuation and dose reduction due to ADRs [Up to 6 Cycles (18 weeks)]
Secondary Outcome Measures
- Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 [Screening, Subsequent Cycles (every 6 weeks), EOT (up to 18 weeks)]
- Disease control rate (DCR) based on RECIST v1.1 [Screening, Subsequent Cycles (every 6 weeks), EOT (up to 18 weeks)]
- Disease control rate (DCR) based on Immune RECIST (iRECIST) [Screening, Subsequent Cycles (every 6 weeks), EOT (up to 18 weeks)]
- Duration of response (DOR) based on RECIST v1.1 [Screening, Subsequent Cycles (every 6 weeks), EOT (up to 18 weeks)]
- Duration of response (DOR) based on iRECIST [Screening, Subsequent Cycles (every 6 weeks), EOT (up to 18 weeks)]
- Overall survival (OS) [every 12 weeks after EOT (18 weeks)]
- Progression free survival (PFS) based on RECIST v1.1 [Screening, Subsequent Cycles (every 6 weeks), EOT (up to 18 weeks)]
- Progression free survival (PFS) based on iRECIST [Screening, Subsequent Cycles (every 6 weeks), EOT (up to 18 weeks)]
- Target tumor size [Screening, Subsequent Cycles (every 6 weeks), EOT (up to 18 weeks)]
Maximum rate of change in the sum of the maximum length of the target lesion For target tumor size, the number of subjects, average, standard deviation, median, minimum, and maximum values by each dosing group are presented.
- Time to progression (TTP), time to response (TTR), time to failure (TTF), and other assessable efficacy endpoints [Screening, Subsequent Cycles (every 6 weeks), EOT (up to 18 weeks)]
- Maximum Concentration (Cmax) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Maximum Concentration at steady state (Cmax,ss) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Minimum Concentration (Cmin) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Minimum Concentration at steady state (Cmin,ss) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Average Concentration at steady state (Cav,ss) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Area under the curve (AUC) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Area under the curve (AUC) from 0 to infinity of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Time to maximum concentration of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Time to maximum concentration at steady state of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Half life of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Peak trough fluctuation (PTF) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Accumulation ratio (AR) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Clearance rate (CL) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Volume of distribution (Vz) of WM-A1-3389 or WM-A1-3389 with Pembrolizumab [Cycle 1, Cycle 2, Subsequent Cycles up to EOT (up to 18 weeks)]
- Number of participants with anti-WM-A1-3389 antibodies (Stage 1 only) [Up to EOT (up to 18 weeks)]
Eligibility Criteria
Criteria
Inclusion Criteria:
[Stage 1: monotherapy]
-
Be ≥19 years of age
-
histologically or cytologically confirmed diagnosis of unresectable advanced or metastatic solid tumors which has progressed after treatment with standard therapy(s) or for which no further standard therapy is available due to intolerance or incompatibility to standard therapies
-
IGSF1 positive expression
-
Have at least one measurable lesion based on RECIST v1.1
-
Have ECOG performance status of 0 or 1
-
Have life expectancy of at least 12 weeks
-
Have adequate organ functions defined as follow (examination with abnormal result may be retested once while the screening phase is underway)
-
Absolute neutrophil count (ANC) ≥ 1500/mm3
-
Platelet count ≥ 100,000/mm3
-
Hemoglobin (Hb) ≥ 9 g/dL
-
Total bilirubin ≤ 1.5 X Institutional Upper Limit of Normal (IULN) (this does not apply to patients with Gilbert's syndrome.)
-
Serum creatinine ≤ 1.5 X IULN
-
Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) ≤ 2.5 X IULN (or, if liver metastasis is found, AST and ALT ≤ 5 X IULN)
-
Prothrombin time (PT) ≤ 1.5 X IULN *IULN: Institutional Upper Limit of Normal
-
Have agreed to provide archival tumor sample collected within 3 months before screening or conduct tumor biopsy at pre-treatment
-
Have agreed to receive up to two on-treatment biopsies
-
Have expressed his/her voluntary agreement and provide written informed consent based on an understanding of the sufficient information to the study.
[Stage 2: Combination therapy]
-
Be ≥ 19 years of age
-
histologically or cytologically confirmed diagnosis of unresectable advanced or metastatic NSCLC
-
has progressed after standard therapy(s) or no further standard therapy is available due to intolerance or incompatibility to standard therapies
-
has progressed during or after anticancer therapy with anti-PD-1/L1
-
IGSF1 positive expression
-
PD-L1 low or negative expression (TPS < 50%)
-
Have at least one measurable lesion based on RECIST v1.1
-
Have ECOG performance status score of 0 or 1
-
Have life expectancy of at least 12 weeks
-
Have adequate organ functions defined as follow (examination with abnormal result may be retested once while the screening phase is underway)
-
Absolute neutrophil count (ANC) ≥ 1500/mm3
-
Platelet count ≥ 100,000/mm3
-
Hemoglobin (Hb) ≥ 9 g/dL
-
Total bilirubin ≤ 1.5 X IULN (this does not apply to patients with Gilbert's syndrome.)
-
Serum creatinine ≤ 1.5 X IULN
-
Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) ≤ 2.5 X IULN (or, if liver metastasis is found, AST and ALT ≤ 5 X IULN)
-
Prothrombin time (PT) ≤ 1.5 X IULN *IULN: Institutional Upper Limit of Normal
-
Have agreed to provide archival tumor sample collected within 3 months before screening or conduct tumor biopsy at pre-treatment
-
Have agreed to receive up to two on-treatment biopsies
-
Have expressed his/her voluntary agreement and provide written informed consent based on an understanding of the sufficient information to the study.
Exclusion Criteria:
[Common]
-
Have experienced hypersensitivity to Investigational Product (IP), any of its excipients or other monoclonal antibody
-
Have a history of diseases, surgical procedure, or operation as below
-
Other primary malignant tumor (subject neither having received any treatment nor experienced the disease progression within 3 years can be enrolled) or hematologic malignancy
-
Major surgery within 4 weeks or minor surgery within 2 weeks before the IP administration
-
Clinically significant arrhythmia, acute myocardial infarction, unstable angina or New York Heart Association (NYHA) class Ⅲ or Ⅳ heart failure within 6 months before IP administration
-
Severe cerebrovascular disease within 6 months before IP administration
-
Pulmonary thrombosis, deep vein thrombosis, bronchial asthma, obstructive pulmonary disease, other severe or life-threatening pulmonary diseases (e.g., acute respiratory distress syndrome, lung failure), considered inappropriate for the subject, within 6 months before IP administration
-
Infection that requires systemic antibiotics, antiviral agents, etc. or Grade 3 or severer active infectious disease within 2 weeks before IP administration
-
Risk factors of ileus or gastrointestinal perforation (including but not limited to acute diverticulitis, intra-abdominal abscess or abdominal carcinomatosis)
-
Auto-immune diseases
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Have any of the following diseases
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Metastasis to the central nervous system that is uncontrolled or with clinically significant symptoms (unless systemic use of corticosteroid is stopped 4 weeks before IP administration, and clinically stable over 4 weeks)
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Abnormal ECG regarded as clinically significant by the investigator
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Uncontrolled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg)
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Active infection that requires treatment
-
Active hepatitis B or C virus
-
Human immunodeficiency virus infection (HIV) positive
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Symptomatic ascites or pleural effusion (unless clinically stable after treatment)
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Any diseases affecting the results of the study, deemed by investigator
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Have history of medications or therapies as follow
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Anticancer therapy such as chemotherapy, hormone therapy, targeted therapy and radiation therapy within the past 4 weeks from IP administration
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Immunotherapy such as anti-PD-1/L1 or anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) within the past 4 weeks from IP administration
-
Live attenuated vaccine within the past 4 weeks from IP administration
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Immunosuppressants or immunomodulators within the past 4 weeks from IP administration (except for immunosuppressants used in prevention or treatment of adverse events, nonsystemic corticosteroids, prednisolone 10 mg/day or under equivalent dose of systemic corticosteroids)
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Bone marrow or organ transplantation
-
Pregnant women, lactating women or any men/women in child-bearing age who are not willing to maintain sexual abstinence or use appropriate contraceptive method*, or do not consent to refrain from donation sperm/ova for at least 6 months from the date of IP administration
- Appropriate contraceptive method
-
Oral or injectable hormone therapy
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Intrauterine device or system implant
-
Male or female sterilization (vasectomy, tubal ligation, etc.)
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Have received any other IP or implantation of investigational medical device within the past 4 weeks from IP administration
-
Inappropriate or impossible to participate in the study, deemed by investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Seoul St. Mary's Hospital | Seoul | Seocho-gu | Korea, Republic of | 06591 |
| 2 | Incheon St. Mary's Hospital | Incheon | Yeonsu-gu | Korea, Republic of | 21999 |
Sponsors and Collaborators
- Wellmarker Bio
- Merck Sharp & Dohme LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WMA13389-101