計劃書編號KY1044-CT01
試驗已結束
2019-01-01 - 2023-09-30
Phase I
召募中2
終止收納4
A Phase 1/2, open-label, multi-center study of the safety and efficacy of KY1044 as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with selected advanced malignancies
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試驗申請者
保瑞爾生技股份有限公司
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試驗委託 / 贊助單位名稱
保瑞爾生技股份有限公司(PRA Taiwan Inc.)
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臨床試驗規模
多國多中心
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更新日期
2026/04/01
試驗主持人及試驗醫院
實際收案人數
0 召募中
Audit
無
實際收案人數
0 召募中
實際收案人數
0 終止收納
實際收案人數
0 終止收納
適應症
Advanced/metastatic malignancies, and preferred indications: head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC),
hepatocellular carcinoma (HCC), esophageal cancer, gastric cancer, melanoma,
renal cell cancer, pancreatic cancer, cervical cancer, and triple negative breast
cancer (BC)
試驗目的
Primary objectives
.Phase 1: to characterize the safety and tolerability of KY1044 as single agent and in combination with atezolizumab and to identify recommended doses for future studies.
.Phase 2: to estimate the anti-tumor efficacy of KY1044 as single agent and in combination with atezolizumab
藥品名稱
Injection
主成份
KY1044
劑型
Injection
劑量
50mg/mL
評估指標
Phase 1:
• Safety: Incidence and severity of AEs and SAEs, including changes in
laboratory parameters, vital signs and ECGs
• Tolerability: Dose interruptions, reductions and dose intensity
• The incidence of Dose Limiting Toxicities (DLTs) with KY1044 as single
agent during the first 21 days of treatment
• The incidence of DLTs with KY1044 in combination with atezolizumab during
the first 21 days of treatment
Phase 2:
• Overall response rate (ORR) per RECIST 1.1
• Safety: Incidence and severity of AEs and SAEs, including changes in
laboratory parameters, vital signs and ECGs
• Tolerability: Dose interruptions, reductions and dose intensity
• The incidence of Dose Limiting Toxicities (DLTs) with KY1044 as single
agent during the first 21 days of treatment
• The incidence of DLTs with KY1044 in combination with atezolizumab during
the first 21 days of treatment
Phase 2:
• Overall response rate (ORR) per RECIST 1.1
主要納入條件
inclusion criteria:
1. Histologically documented advanced/metastatic malignancies
2. Phase 1 and Phase 2 patients with advanced/metastatic malignancies who have measurable disease (non-measurable disease is allowed only in Phase 1) as determined by RECIST 1.1 will be eligible if, according to the NCCN guidelines, there are no available therapies known to confer a clinical benefit for their disease, or they have exhausted all such available options.
Additionally, the following specific tumor indications will be enrolled:
a. Phase 1 (including enrichment part):
Patients with advanced/metastatic malignancies, and preferred indications (NSCLC, HNSCC, HCC, melanoma, cervical, esophageal, gastric, renal, pancreatic, and triple negative BC)
b. Phase 2 KY1044 single agent:
Patients with advanced/metastatic malignancies in indications in which signs of anti-tumor activity (CR, PR or durable SD with tumor shrinkage that does not qualify for PR) were seen during the dose escalation of KY1044 as single agent.
c. Phase 2 KY1044 in combination with atezolizumab:
Patients with advanced/metastatic malignancies in the selected indications below, and/or indications which have shown promising activity in Phase 1:
• NSCLC (anti-PD-(L)1 therapy naïve and pre-treated)
• HNSCC (anti-PD-(L)1 therapy naïve and pre-treated)
• Gastric (anti-PD-(L)1 therapy naïve and pre-treated)
• Esophageal cancer (anti-PD-(L)1 therapy naïve and pre-treated)
• Cervical cancer (anti-PD-(L)1 therapy naïve and pre-treated)
• Indications, in which signs of anti-tumor activity has been observed
in Phase 1 with KY1044 in combination with atezolizumab
3. Prior therapy with anti-PD-(L)1 inhibitors is allowed provided any toxicity attributed to prior anti-PD-(L)1-directed therapy did not lead to discontinuation of therapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Life expectancy longer than 12 weeks
6. Must have a site of disease amendable to biopsy, and be candidate for tumor biopsy, according to the treating institution’s guidelines. Patients must be willing to undergo a new tumor biopsy at screening and during therapy on the study
7. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
exclusion criteria:
1. Presence of symptomatic central nervous system (CNS) metastases unless neurologically stable (for 4 weeks) and off steroids for at least 2 weeks before the first dose of study treatment.
2. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs) and/or their excipients.
3. Known presence of neutralizing anti-atezolizumab antibodies
4. Patients previously exposed to anti-PD-(L)1 treatment who are not adequately treated for skin rash or have no replacement therapy for endocrinopathies
5. Known human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. Patients with HCC, whose HBV or HCV infection is controlled by antiviral therapy, should not be excluded.
6. Active autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn’s disease or any condition that requires systemic steroids.
7. Malignant disease, other than that being treated in this study. Exceptions to this exclusion criterion include malignancies that were treated curatively and have not recurred within 2 years prior to the first dose of study treatment; completely resected basal cell and squamous cell skin cancers; and completely resected carcinoma in situ of any type.
8. Systemic steroid therapy or any immunosuppressive therapy (≥10 mg/day prednisone or equivalent).
9. Anti-CTLA4, anti-PD-(L)1 treatment within 4 weeks of the first dose of study treatment
10. Pretreatment with anti-CTLA4 antibodies in combination with other antibodies or drugs, specifically targeting T-cell stimulation or checkpoint pathways.
11. Systemic anti-cancer therapy (tyrosine kinase inhibitor (TKI) and/or chemotherapy) within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosourea, 4 weeks is indicated as washout period.
12. Use of life attenuated vaccines against infectious diseases (e.g. measles mumps rubella (MMR combined vaccines), Rotavirus, Chickenpox, yellow fever) within 4 weeks of initiation of study treatment.
13. Participation in an interventional, investigational study within 4 weeks of the first dose of study treatment.
14. Impaired cardiac function or clinically significant cardiac disease, including any of the following:
a. Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association (NYHA) Grade ≥2), uncontrolled hypertension or clinically significant arrhythmia
b. QTcF >470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome
c. Acute myocardial infarction or unstable angina pectoris <3 months prior to first dose of study treatment
15. Presence of Common Terminology Criteria for Adverse Events Version 5 (CTCAE v5) ≥Grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if CTCAE v5 ≥Grade 3) due to prior cancer therapy.
16. Radiotherapy within 2 weeks of the first dose of study treatment, except for palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass. To allow evaluation for response to treatment, patients enrolled in the Phase 2 part must have remaining measurable disease that has not been irradiated.
1. Histologically documented advanced/metastatic malignancies
2. Phase 1 and Phase 2 patients with advanced/metastatic malignancies who have measurable disease (non-measurable disease is allowed only in Phase 1) as determined by RECIST 1.1 will be eligible if, according to the NCCN guidelines, there are no available therapies known to confer a clinical benefit for their disease, or they have exhausted all such available options.
Additionally, the following specific tumor indications will be enrolled:
a. Phase 1 (including enrichment part):
Patients with advanced/metastatic malignancies, and preferred indications (NSCLC, HNSCC, HCC, melanoma, cervical, esophageal, gastric, renal, pancreatic, and triple negative BC)
b. Phase 2 KY1044 single agent:
Patients with advanced/metastatic malignancies in indications in which signs of anti-tumor activity (CR, PR or durable SD with tumor shrinkage that does not qualify for PR) were seen during the dose escalation of KY1044 as single agent.
c. Phase 2 KY1044 in combination with atezolizumab:
Patients with advanced/metastatic malignancies in the selected indications below, and/or indications which have shown promising activity in Phase 1:
• NSCLC (anti-PD-(L)1 therapy naïve and pre-treated)
• HNSCC (anti-PD-(L)1 therapy naïve and pre-treated)
• Gastric (anti-PD-(L)1 therapy naïve and pre-treated)
• Esophageal cancer (anti-PD-(L)1 therapy naïve and pre-treated)
• Cervical cancer (anti-PD-(L)1 therapy naïve and pre-treated)
• Indications, in which signs of anti-tumor activity has been observed
in Phase 1 with KY1044 in combination with atezolizumab
3. Prior therapy with anti-PD-(L)1 inhibitors is allowed provided any toxicity attributed to prior anti-PD-(L)1-directed therapy did not lead to discontinuation of therapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Life expectancy longer than 12 weeks
6. Must have a site of disease amendable to biopsy, and be candidate for tumor biopsy, according to the treating institution’s guidelines. Patients must be willing to undergo a new tumor biopsy at screening and during therapy on the study
7. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
exclusion criteria:
1. Presence of symptomatic central nervous system (CNS) metastases unless neurologically stable (for 4 weeks) and off steroids for at least 2 weeks before the first dose of study treatment.
2. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs) and/or their excipients.
3. Known presence of neutralizing anti-atezolizumab antibodies
4. Patients previously exposed to anti-PD-(L)1 treatment who are not adequately treated for skin rash or have no replacement therapy for endocrinopathies
5. Known human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. Patients with HCC, whose HBV or HCV infection is controlled by antiviral therapy, should not be excluded.
6. Active autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn’s disease or any condition that requires systemic steroids.
7. Malignant disease, other than that being treated in this study. Exceptions to this exclusion criterion include malignancies that were treated curatively and have not recurred within 2 years prior to the first dose of study treatment; completely resected basal cell and squamous cell skin cancers; and completely resected carcinoma in situ of any type.
8. Systemic steroid therapy or any immunosuppressive therapy (≥10 mg/day prednisone or equivalent).
9. Anti-CTLA4, anti-PD-(L)1 treatment within 4 weeks of the first dose of study treatment
10. Pretreatment with anti-CTLA4 antibodies in combination with other antibodies or drugs, specifically targeting T-cell stimulation or checkpoint pathways.
11. Systemic anti-cancer therapy (tyrosine kinase inhibitor (TKI) and/or chemotherapy) within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosourea, 4 weeks is indicated as washout period.
12. Use of life attenuated vaccines against infectious diseases (e.g. measles mumps rubella (MMR combined vaccines), Rotavirus, Chickenpox, yellow fever) within 4 weeks of initiation of study treatment.
13. Participation in an interventional, investigational study within 4 weeks of the first dose of study treatment.
14. Impaired cardiac function or clinically significant cardiac disease, including any of the following:
a. Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association (NYHA) Grade ≥2), uncontrolled hypertension or clinically significant arrhythmia
b. QTcF >470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome
c. Acute myocardial infarction or unstable angina pectoris <3 months prior to first dose of study treatment
15. Presence of Common Terminology Criteria for Adverse Events Version 5 (CTCAE v5) ≥Grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if CTCAE v5 ≥Grade 3) due to prior cancer therapy.
16. Radiotherapy within 2 weeks of the first dose of study treatment, except for palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass. To allow evaluation for response to treatment, patients enrolled in the Phase 2 part must have remaining measurable disease that has not been irradiated.
試驗計畫預計收納受試者人數
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台灣人數
75 人
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全球人數
412 人
