A Phase 1 Study of ASKG315 in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
The study is a Phase 1, open-label, multicenter, dose escalation study to evaluate the safety, tolerability, PK and PD of ASKG315 as a single agent (Part 1) and in combination with pembrolizumab (Part 2) in patients with advanced solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Each part of the study consists of 3 periods: screening (up to 28 days), treatment and follow-up. After an initial screening period, ASKG315 or ASKG315 combined with pembrolizumab will be administered once every 3 weeks by intravenous (IV) infusion. The Part 1 dose escalation consists of 6 planned escalation cohorts, with a starting dose of 3 mg. The Part 2 dose escalation consists of 4 planned escalation cohorts.
Part 2 of the study will begin enrolling after Part 1 has successfully and safely dosed all patients in the first two cohorts and followed these patients through the entire DLT period. The starting dose of Part 2 will be determined according to the safety and PK of ASKG315 in Part 1 of the study, but in no case will it exceed the highest dose already safely administered in Part 1 and confirmed as tolerable by the Safety Review Committee in Part 1.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ASKG315 Single or multiple ascending dose of ASKG315 |
Biological: ASKG315
Injection with dose escalation stage of 3mg up to 45mg as well as dose expansion stage with recommended dose level from dose escalation stage.
|
Outcome Measures
Primary Outcome Measures
- Safety[DLTs、AEs、ECG] [21days]
Incidence of dose limiting toxicities (DLTs) Incidence of adverse events (AEs), laboratory abnormalities, and ECG abnormalities
Secondary Outcome Measures
- Maximum plasma concentration (Cmax) [21days]
To evaluate the systemic pharmacokinetics of ASKG315 in subjects.
- Area under the concentration time curve (AUC) [21days]
To evaluate the systemic pharmacokinetics of ASKG315 in subjects.
- Cytokine [21days]
Increase in circulating cytokine levels.
- Immunocyte [21days]
Changes in immunocyte levels by flow cytometry.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed informed consent form.
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Male or female ≥ 18 years of age (at the time signed consent is obtained).
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Histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available.
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Measurable disease, per RECIST v1.1.
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ECOG Performance Status of ≤ 2.
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Life expectancy of ≥3 months, in the opinion of the Investigator.
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Adequate organ function defined.
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Fertile patients must be willing to use effective contraceptive measures (hormonal or barrier methods or abstinence, etc.) starting with the Screening visit through 90 days
- 5 drug half-lives after the last dose of study treatment.
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Negative serum pregnancy test for female patients within 7 days prior to the first dose of the study drug or documentation of lack of childbearing potential.
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Willing and able to participate in the trial and comply with all trial requirements.
Exclusion Criteria:
Patients who meet any of the following criteria are not allowed to be enrolled:
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Received any other investigational drug for treatment that is not commercially available within 4 weeks prior to Cycle 1 Day 1.
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Received chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, or any other anti-tumor treatments within 4 weeks prior to Cycle 1 Day
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Had major organ surgery or significant trauma within 4 weeks prior to C1D1 or planning elective surgery during the study period.
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Received systemic glucocorticoid or other immunosuppressant treatment within 14 days prior to C1D1.
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Received immunomodulatory drugs, including but not limited to thymosin and interferon, within 14 days prior to C1D1.
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Received a live attenuated vaccine within 4 weeks prior to C1D1.
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Received IL-2 or IL-15 therapy within 12 weeks prior to C1D1.
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History of hematologic stem cell transplant or solid organ transplant.
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Adverse reactions to previous antitumor therapy have not recovered to CTCAE 5.0 grade ≤ 1.
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Cerebral parenchymal metastasis or meningeal metastasis with clinical symptoms.
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Have an active infection that currently requires intravenous anti-infection therapy.
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A history of human immunodeficiency virus (HIV) infection with a CD4+ T-cell count of ≤350 cells/µL at screening. HIV positive patients must be receiving adequate treatment.
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If serological evidence of chronic hepatitis B virus infection (HBV), viral load below the limit of quantification at screening.
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If serological evidence of hepatitis C virus infection (HCV), should have completed curative antiviral treatment and have HCV viral load below the limit of quantification at screening.
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Current clinically significant interstitial lung disease.
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History of serious cardiovascular or cerebrovascular diseases.
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Active or recurrent autoimmune diseases.
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History of Grade ≥ 3 Immune-Related Adverse Events (irAE) or Grade ≥ 2 immunotherapy-associated myocarditis associated with treatment with an immune checkpoint inhibitor.
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Grade ≥ 3 bleeding .
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Symptomatic with uncontrolled ascites or pleural effusion.
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History of a grade ≥ 3 allergic reaction to protein drugs.
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Known to have alcohol or drug dependence.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- AskGene Pharma, Inc.
- Jiangsu Aosaikang Pharmaceutical Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ASKG315-101