計劃書編號THIO-101
試驗執行中
2024-12-01 - 2027-12-31
Phase II
召募中10
ICD-10C33
氣管惡性腫瘤
ICD-10Z51.12
來院接受抗腫瘤免疫療法
ICD-9162.0
氣管惡性腫瘤
一項多中心、開放性、劑量探索、第 2 期試驗，在罹患晚期非小細胞肺癌 (NSCLC) 的受試者中，評估 THIO 接續給予 Cemiplimab (LIBTAYO®) 的治療
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試驗申請者
晉加股份有限公司
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試驗委託 / 贊助單位名稱
晉加股份有限公司
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臨床試驗規模
多國多中心
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更新日期
2026/02/01
試驗主持人及試驗醫院
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 召募中
適應症
A 部分：DLT 發生率 A 部分和 B 部分：不作區分、依據嚴重程度區分、依據與 THIO 和／或 cemiplimab 之關係區分的 TEAE 和 SAE，以及導致停用 THIO 和 cemiplimab 和／或退出試驗之 TEAE 和 SAE 的發生率•ORR，定義為由試驗主持人根據 RECIST 版本 1.1 評估達到 CR 或 PR 的受試者比例•DCR，定義為由試驗主持人根據 RECIST 版本 1.1 評估達到 CR、PR 或 SD 的受試者比例C部分ORR，定義為由試驗主持人根據 RECIST 版本 1.1 評估達到 CR 或 PR 的受試者比例D部分ORR，定義為由 BICR 根據 RECIST 版本 1.1 評估達到經確認 CR 或 PR 的受試者比例
試驗目的
•A 部分：依據劑量限制毒性 (DLT) 的觀察發生率和剖析結果，確定 THIO 在接續給予固定劑量 cemiplimab 時用於晚期 NSCLC 受試者的安全劑量等級。
•B 部分：依據晚期 NSCLC 受試者的安全性、耐受性和療效評估結果，選擇 THIO 在接續給予固定劑量 cemiplimab 時的最佳劑量。
•C 部分：對於晚期／轉移性 NSCLC 受試者，取得每個週期給予 THIO 180 mg 加上 cemiplimab 之接續併用療法，相較於每個週期給予單一藥物 THIO 180 mg 作為第三線治療之療效和安全性的臨床證據。
•D 部分：確定以每個週期 THIO 180 mg（在第 1 至 3 天給予 60 mg，接續給予 cemiplimab）作為晚期／轉移性 NSCLC 受試者第三線治療時的療效。
藥品名稱
靜脈點滴注射劑
靜脈點滴注射劑
靜脈點滴注射劑
主成份
THIO
cemiplimab
cemiplimab
劑型
242
242
242
劑量
20MG/8ML
350mg/7ml
350mg/7ml
評估指標
A 部分：DLT 發生率
A 部分和 B 部分：不作區分、依據嚴重程度區分、依據與 THIO 和／或 cemiplimab 之關係區分的 TEAE 和 SAE，以及導致停用 THIO 和 cemiplimab 和／或退出試驗之 TEAE 和 SAE 的發生率
•ORR，定義為由試驗主持人根據 RECIST 版本 1.1 評估達到 CR 或 PR 的受試者比例
•DCR，定義為由試驗主持人根據 RECIST 版本 1.1 評估達到 CR、PR 或 SD 的受試者比例
C部分
ORR，定義為由試驗主持人根據 RECIST 版本 1.1 評估達到 CR 或 PR 的受試者比例
D部分
ORR，定義為由 BICR 根據 RECIST 版本 1.1 評估達到經確認 CR 或 PR 的受試者比例
A 部分和 B 部分：不作區分、依據嚴重程度區分、依據與 THIO 和／或 cemiplimab 之關係區分的 TEAE 和 SAE，以及導致停用 THIO 和 cemiplimab 和／或退出試驗之 TEAE 和 SAE 的發生率
•ORR，定義為由試驗主持人根據 RECIST 版本 1.1 評估達到 CR 或 PR 的受試者比例
•DCR，定義為由試驗主持人根據 RECIST 版本 1.1 評估達到 CR、PR 或 SD 的受試者比例
C部分
ORR，定義為由試驗主持人根據 RECIST 版本 1.1 評估達到 CR 或 PR 的受試者比例
D部分
ORR，定義為由 BICR 根據 RECIST 版本 1.1 評估達到經確認 CR 或 PR 的受試者比例
主要納入條件
Age
1.At least 18 years of age at the time of signing the Informed Consent Form (ICF) prior to initiation of any study specific activities/procedures.
Type of Subject and Disease Characteristics
2.Stage 3 or 4 histologically or cytologically confirmed NSCLC which has progressed or relapsed after treatment in the advanced setting
○Stage 4 subjects:
Part A and Part B: must have progressed or relapsed after first line treatment.
Part C and Part D: must have progressed, discontinued due to toxicity, or relapsed after receiving (only) two prior lines of treatment for NSCLC in the advanced setting.
○Stage 3 subjects – must have already failed, or be ineligible for, local, curative-intent therapy including surgery, and/or chemoradiation. Stage 3 subjects with documented relapse/progression after consolidation therapy with durvalumab following definitive chemoradiotherapy are eligible.
3.Subjects must have secondary resistance to the prior ICI, as defined by the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Task Force (IRTF) (Kluger 2020):
4.Part A and Part B: Only one prior treatment for NSCLC in the advanced setting, which must have included one anti-PD-1/PD-L1 agent with documented radiographic disease progression on or after treatment.
○Prior treatment may have been with anti-PD-1/PD-L1 agent either alone or in combination with a non-anti-PD-1/PD-L1 treatment (e.g., chemotherapy)
○Prior platinum-based chemotherapy is not required for eligibility.
○Subjects receiving more than one ICI in the advanced setting (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds) will not be eligible.
Part C and Part D: Only two prior treatments for NSCLC in the advanced setting, which must have included an anti-PD-1/PD-L1 agent, a platinum-based chemotherapy, and docetaxel, regardless of order or combination, with documented radiographic disease progression, intolerable toxicity, or relapse after treatment.
○Combination of immune therapy is allowed (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds; anti-PD-1/PD-L1 and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT)-based immunotherapy).
5.No prior targeted therapy for driver mutations.
6.At least one measurable target lesion that meets the definition of RECIST v1.1.
7.Part A and Part B: An archival tissue sample (formalin fixed paraffin-embedded [FFPE] tissue block or unstained slides) is required if tissue is available at baseline. Sample does not need to be received by central lab prior to Cycle 1, Day 1 (C1D1). Subjects without archival tissue available at baseline may be eligible with Medical Monitor approval.
Part C and Part D: Archival tissue is not required.
Diagnostic Assessments
8.Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
9.Demonstrate adequate organ function as defined below. All screening laboratories should be performed up to 14 days before initiating IP:
Bone marrow function:
○Neutrophil count ≥ 1500/mm3, hemoglobin ≥ 9.0 g/dL, platelet count ≥ 100,000/mm3
Liver function:
○Total bilirubin ≤ 1.5 x the upper limit of normal (ULN), up to ≤ 3 × ULN due to Gilbert’s syndrome
○Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN. For subjects with liver metastases present at baseline, ALT and/or AST ≤ 3 × ULN is permitted.
Renal function:
○Creatinine clearance ≥ 60 mL/min calculated by the Cockcroft-Gault formula using actual body weight (see Table 15) or 24-hour urine collection. For Asian countries, a creatinine clearance of ≥ 50 mL/min calculated by the Cockcroft-Gault formula using actual body weight (see Table 15) or 24-hour urine collection is acceptable.
Gender and Reproductive Considerations
10.Women of childbearing potential (WOCBP) must have negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to receiving the first administration of IP.
11.Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Refer to Appendix 4, Section 10.4 for details and definitions of WOCBP, postmenopausal females and contraception guidance.
12.WOCBP must agree to use a highly effective birth control and refrain from oocyte donation during the study (prior to the first dose with THIO, for the duration of the treatment with THIO plus 6 months after last dose of IP), if conception is possible during this interval.
13.Male subjects and WOCBP partners of male subjects should use a combination of the methods specified in Section 10.4 for the women along with a male condom from first dose of THIO (Cycle 1, Day 1), for the duration of the treatment with THIO plus 6 months after last dose of IP, unless permanently sterile by bilateral orchidectomy. Male subjects should also refrain from sperm donation during this time.
Informed Consent
14.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
1.At least 18 years of age at the time of signing the Informed Consent Form (ICF) prior to initiation of any study specific activities/procedures.
Type of Subject and Disease Characteristics
2.Stage 3 or 4 histologically or cytologically confirmed NSCLC which has progressed or relapsed after treatment in the advanced setting
○Stage 4 subjects:
Part A and Part B: must have progressed or relapsed after first line treatment.
Part C and Part D: must have progressed, discontinued due to toxicity, or relapsed after receiving (only) two prior lines of treatment for NSCLC in the advanced setting.
○Stage 3 subjects – must have already failed, or be ineligible for, local, curative-intent therapy including surgery, and/or chemoradiation. Stage 3 subjects with documented relapse/progression after consolidation therapy with durvalumab following definitive chemoradiotherapy are eligible.
3.Subjects must have secondary resistance to the prior ICI, as defined by the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Task Force (IRTF) (Kluger 2020):
4.Part A and Part B: Only one prior treatment for NSCLC in the advanced setting, which must have included one anti-PD-1/PD-L1 agent with documented radiographic disease progression on or after treatment.
○Prior treatment may have been with anti-PD-1/PD-L1 agent either alone or in combination with a non-anti-PD-1/PD-L1 treatment (e.g., chemotherapy)
○Prior platinum-based chemotherapy is not required for eligibility.
○Subjects receiving more than one ICI in the advanced setting (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds) will not be eligible.
Part C and Part D: Only two prior treatments for NSCLC in the advanced setting, which must have included an anti-PD-1/PD-L1 agent, a platinum-based chemotherapy, and docetaxel, regardless of order or combination, with documented radiographic disease progression, intolerable toxicity, or relapse after treatment.
○Combination of immune therapy is allowed (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds; anti-PD-1/PD-L1 and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT)-based immunotherapy).
5.No prior targeted therapy for driver mutations.
6.At least one measurable target lesion that meets the definition of RECIST v1.1.
7.Part A and Part B: An archival tissue sample (formalin fixed paraffin-embedded [FFPE] tissue block or unstained slides) is required if tissue is available at baseline. Sample does not need to be received by central lab prior to Cycle 1, Day 1 (C1D1). Subjects without archival tissue available at baseline may be eligible with Medical Monitor approval.
Part C and Part D: Archival tissue is not required.
Diagnostic Assessments
8.Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
9.Demonstrate adequate organ function as defined below. All screening laboratories should be performed up to 14 days before initiating IP:
Bone marrow function:
○Neutrophil count ≥ 1500/mm3, hemoglobin ≥ 9.0 g/dL, platelet count ≥ 100,000/mm3
Liver function:
○Total bilirubin ≤ 1.5 x the upper limit of normal (ULN), up to ≤ 3 × ULN due to Gilbert’s syndrome
○Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN. For subjects with liver metastases present at baseline, ALT and/or AST ≤ 3 × ULN is permitted.
Renal function:
○Creatinine clearance ≥ 60 mL/min calculated by the Cockcroft-Gault formula using actual body weight (see Table 15) or 24-hour urine collection. For Asian countries, a creatinine clearance of ≥ 50 mL/min calculated by the Cockcroft-Gault formula using actual body weight (see Table 15) or 24-hour urine collection is acceptable.
Gender and Reproductive Considerations
10.Women of childbearing potential (WOCBP) must have negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to receiving the first administration of IP.
11.Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Refer to Appendix 4, Section 10.4 for details and definitions of WOCBP, postmenopausal females and contraception guidance.
12.WOCBP must agree to use a highly effective birth control and refrain from oocyte donation during the study (prior to the first dose with THIO, for the duration of the treatment with THIO plus 6 months after last dose of IP), if conception is possible during this interval.
13.Male subjects and WOCBP partners of male subjects should use a combination of the methods specified in Section 10.4 for the women along with a male condom from first dose of THIO (Cycle 1, Day 1), for the duration of the treatment with THIO plus 6 months after last dose of IP, unless permanently sterile by bilateral orchidectomy. Male subjects should also refrain from sperm donation during this time.
Informed Consent
14.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
主要排除條件
Medical Conditions
1.Have not recovered from adverse events (must be Grade ≤ 1) due to prior anti-cancer treatment.
2.Untreated or symptomatic central nervous system (CNS) metastases.
Note: subjects with treated asymptomatic brain metastasis are eligible.
3.Active gastrointestinal bleeding as evidenced by either hematemesis or melena.
4.History of another concurrent malignancy other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years.
5.A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, adrenal replacement doses 10 mg daily prednisone equivalents, and systemic corticosteroids to manage adverse events (AEs) are permitted in the absence of active autoimmune disease.
6.Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of screening.
7.Positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B or hepatitis C.
8.Significant cardiovascular impairment (history of New York Heart Association Functional Classification System Class III or IV) or a history of myocardial infarction or unstable angina within the past 6 months prior to IP initiation.
a)QTcF > 480 msec at screening (based on average of triplicate ECGs at baseline).
i.If the QTc is prolonged in a subject with a pacemaker or bundle branch block, the subject may be enrolled in the study if confirmed by the Medical Monitor.
9.Ongoing immune-related/stimulated adverse events (irAEs) from other agents or required permanent discontinuation of prior ICIs due to irAEs. Subjects with resolved irAE may be allowed to enroll following consultation with Sponsor’s Medical Monitor (or designee).
10.Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions:
○Controlled type 1 diabetes;
○Hypothyroidism (provided it is managed with hormone replacement therapy only);
○Controlled celiac disease;
○Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia);
○Any other disease that is not expected to recur in the absence of external triggering factors.
11.Pregnancy or lactating.
12.A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor.
13.Any other condition that, in the opinion of the investigator, would prohibit the subject from participating in the study.
Prior Therapy
14.Part C and Part D: more than two prior systemic treatments for advanced disease.
15.Prior chemotherapy and/or non-biologic targeted therapy within 4 weeks, or biologic targeted therapy, immunotherapy, and/or radiation therapy within 6 weeks prior to Cycle 1 Day 1. Subjects who receive targeted radiation therapy for localized palliative care may be eligible to start treatment < 6 weeks with Medical Monitor agreement.
16.Part A and Part B: Prior treatment with cemiplimab.
Note: Part C and Part D: prior cemiplimab is permitted.
17.For subjects who have received prior treatment with an ICI: primary resistance to prior ICI therapy, as defined by the SITC IRTF (Kluger 2020):
18.Undergone major surgery within 4 weeks prior to Cycle 1, Day 1.
19.Received blood, red blood cell or platelet transfusion within 2 weeks before the first dose of IP.
20.Any live, attenuated, inactivated or research vaccines within 30 days prior to the first dose of IP. Refer to Section 6.9.1 for prohibited vaccines. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed.
21.Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
Prior/Concurrent Clinical Study Experience
22.Currently enrolled in a clinical study involving another IP or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
Other
23.History of allergy to excipients of THIO or cemiplimab.
1.Have not recovered from adverse events (must be Grade ≤ 1) due to prior anti-cancer treatment.
2.Untreated or symptomatic central nervous system (CNS) metastases.
Note: subjects with treated asymptomatic brain metastasis are eligible.
3.Active gastrointestinal bleeding as evidenced by either hematemesis or melena.
4.History of another concurrent malignancy other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years.
5.A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, adrenal replacement doses 10 mg daily prednisone equivalents, and systemic corticosteroids to manage adverse events (AEs) are permitted in the absence of active autoimmune disease.
6.Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of screening.
7.Positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B or hepatitis C.
8.Significant cardiovascular impairment (history of New York Heart Association Functional Classification System Class III or IV) or a history of myocardial infarction or unstable angina within the past 6 months prior to IP initiation.
a)QTcF > 480 msec at screening (based on average of triplicate ECGs at baseline).
i.If the QTc is prolonged in a subject with a pacemaker or bundle branch block, the subject may be enrolled in the study if confirmed by the Medical Monitor.
9.Ongoing immune-related/stimulated adverse events (irAEs) from other agents or required permanent discontinuation of prior ICIs due to irAEs. Subjects with resolved irAE may be allowed to enroll following consultation with Sponsor’s Medical Monitor (or designee).
10.Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions:
○Controlled type 1 diabetes;
○Hypothyroidism (provided it is managed with hormone replacement therapy only);
○Controlled celiac disease;
○Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia);
○Any other disease that is not expected to recur in the absence of external triggering factors.
11.Pregnancy or lactating.
12.A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor.
13.Any other condition that, in the opinion of the investigator, would prohibit the subject from participating in the study.
Prior Therapy
14.Part C and Part D: more than two prior systemic treatments for advanced disease.
15.Prior chemotherapy and/or non-biologic targeted therapy within 4 weeks, or biologic targeted therapy, immunotherapy, and/or radiation therapy within 6 weeks prior to Cycle 1 Day 1. Subjects who receive targeted radiation therapy for localized palliative care may be eligible to start treatment < 6 weeks with Medical Monitor agreement.
16.Part A and Part B: Prior treatment with cemiplimab.
Note: Part C and Part D: prior cemiplimab is permitted.
17.For subjects who have received prior treatment with an ICI: primary resistance to prior ICI therapy, as defined by the SITC IRTF (Kluger 2020):
18.Undergone major surgery within 4 weeks prior to Cycle 1, Day 1.
19.Received blood, red blood cell or platelet transfusion within 2 weeks before the first dose of IP.
20.Any live, attenuated, inactivated or research vaccines within 30 days prior to the first dose of IP. Refer to Section 6.9.1 for prohibited vaccines. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed.
21.Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
Prior/Concurrent Clinical Study Experience
22.Currently enrolled in a clinical study involving another IP or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
Other
23.History of allergy to excipients of THIO or cemiplimab.
試驗計畫預計收納受試者人數
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台灣人數
38 人
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全球人數
227 人
