計劃書編號TCTLR-101
NCT Number(ClinicalTrials.gov Identfier)NCT04799054
試驗已結束
2022-11-30 - 2027-03-31
Phase I/II
召募中4
ICD-10C69.40
未明示側性睫狀體惡性腫瘤
ICD-10C69.41
右側睫狀體惡性腫瘤
ICD-10C69.42
左側睫狀體惡性腫瘤
ICD-10Z51.12
來院接受抗腫瘤免疫療法
ICD-9190.0
眼球(結膜、角膜、視網膜及眼脈絡膜除外)惡性腫瘤
TransCon TLR7/8 促效劑單一療法或併用 Pembrolizumab 用於局部晚期或轉移性實體惡性腫瘤參與者的第 1/2 期、開放性、劑量遞增與劑量擴張試驗
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試驗申請者
全球臨試股份有限公司
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試驗委託 / 贊助單位名稱
全球臨試股份有限公司
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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
適應症
Primary Outcome Measures :1.Safety and Tolerability [ Time Frame: Through study completion, expected average of 2 years ]-Treatment emergent and treatment related adverse events (assessed by CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, deaths2.Maximum Tolerated Dose (MTD) [ Time Frame: Cycle 1 (each cycle is 21 days) in Part 1 (monotherapy dose escalation) and Cycle 1 (the first cycle is 28 days and 21 days thereafter) in Part 2 (combination therapy dose escalation) ]-Determine the maximum tolerated dose by assessing the Incidence of Dose Limiting Toxicities (DLTs), treatment emergent and treatment related adverse events (assessed by CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation and deaths.3.Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 months ]-To determine a recommended phase 2 dose of TransCon TLR7/8 Agonist and combination regimen for further development by evaluating number of patients with treatment-related adverse events as assessed by CTCAE.4.Response [ Time Frame: 9 weeks ]-Evaluate the Pathologic complete response (pCR) per local assessment for pathology review anti-tumor activity of TransCon TLR7/8 Agonist in combination with pembrolizumab in the Neoadjuvant Cohorts
試驗目的
主要目的：
− 評估 TransCon TLR7/8 促效劑單一療法或併用 pembrolizumab 的安全性及耐受性，並界定其最大耐受劑量 (MTD) 和第2 期建議劑量 (RP2D)
− 第 3 部分前導性群組（群組 3c 與 3d）：評估 TransCon TLR7/8 促效劑併用pembrolizumab 的抗腫瘤活性
次要目的：
− 評估 TransCon TLR7/8 促效劑單一療法或併用 pembrolizumab 的抗腫瘤活性
− TransCon TLR7/8 促效劑單一療法或併用pembrolizumab 在 IT 給藥後，進行resiquimod、O-desethyl resiquimod 與總resiquimod (未連結 + 連結) 的血漿藥物動力學 (PK) 特性分析
探索性目的：
− 評估 TransCon TLR7/8 促效劑單一療法或併用 pembrolizumab 在血液與腫瘤中的作用：計算藥效動力學 (PD) 效應並闡明其作用機制
− 第 1 與第 2 部分和第 3 部分群組 3a 與3b：透過腫瘤內細胞程式死亡-配體 1(PD-L1) 的表現來評估療效量測之間的關聯 (由試驗主持人與 ICR 依據 RECIST 1.1 評估的 ORR；由試驗主持人依據itRECIST 評估整體腫瘤負荷、已注射與未注射病灶的 ORR)
− 第 3 部分前導性群組 3c 與 3d：由試驗主持人與 ICR 依據 RECIST 1.1 評估的術前ORR；由試驗主持人依據 itRECIST 評估整體腫瘤負荷、已注射與未注射病灶術前的 ORR
− 第 3 部分前導性群組 3c 與 3d：透過腫瘤內細胞程式死亡-配體 1 (PD-L1) 的表現來評估由當地與中央評估的 pCR 之間關聯
− 第 1 與第 2 部分和第 3 部分群組 3a 與3b：透過 HPV 狀態 (視情況而定且若可取得) 來評估療效量測之間的關聯（由試驗主持人與 ICR 依據 RECIST 1.1 評估的ORR；由試驗主持人依據 itRECIST 評估整體腫瘤負荷、已注射與未注射病灶的ORR）
− 第 3 部分前導性群組 3c 與 3d：透過HPV 狀態 (視情況而定且若可取得) 來評估療效量測之間的關聯（由當地與中央評估的 pCR）
− 進行 resiquimod 代謝物 (如適用) 的血漿PK 特性分析
藥品名稱
注射劑
注射液
注射液
主成份
TransCon TLR7/8 Agonist
Pembrolizumab
Pembrolizumab
劑型
270
279
279
劑量
0.5 mg/mL
25 mg/mL
25 mg/mL
評估指標
Primary Outcome Measures :
1.Safety and Tolerability [ Time Frame: Through study completion, expected average of 2 years ]
-Treatment emergent and treatment related adverse events (assessed by CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, deaths
2.Maximum Tolerated Dose (MTD) [ Time Frame: Cycle 1 (each cycle is 21 days) in Part 1 (monotherapy dose escalation) and Cycle 1 (the first cycle is 28 days and 21 days thereafter) in Part 2 (combination therapy dose escalation) ]
-Determine the maximum tolerated dose by assessing the Incidence of Dose Limiting Toxicities (DLTs), treatment emergent and treatment related adverse events (assessed by CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation and deaths.
3.Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 months ]
-To determine a recommended phase 2 dose of TransCon TLR7/8 Agonist and combination regimen for further development by evaluating number of patients with treatment-related adverse events as assessed by CTCAE.
4.Response [ Time Frame: 9 weeks ]
-Evaluate the Pathologic complete response (pCR) per local assessment for pathology review anti-tumor activity of TransCon TLR7/8 Agonist in combination with pembrolizumab in the Neoadjuvant Cohorts
1.Safety and Tolerability [ Time Frame: Through study completion, expected average of 2 years ]
-Treatment emergent and treatment related adverse events (assessed by CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, deaths
2.Maximum Tolerated Dose (MTD) [ Time Frame: Cycle 1 (each cycle is 21 days) in Part 1 (monotherapy dose escalation) and Cycle 1 (the first cycle is 28 days and 21 days thereafter) in Part 2 (combination therapy dose escalation) ]
-Determine the maximum tolerated dose by assessing the Incidence of Dose Limiting Toxicities (DLTs), treatment emergent and treatment related adverse events (assessed by CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation and deaths.
3.Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 months ]
-To determine a recommended phase 2 dose of TransCon TLR7/8 Agonist and combination regimen for further development by evaluating number of patients with treatment-related adverse events as assessed by CTCAE.
4.Response [ Time Frame: 9 weeks ]
-Evaluate the Pathologic complete response (pCR) per local assessment for pathology review anti-tumor activity of TransCon TLR7/8 Agonist in combination with pembrolizumab in the Neoadjuvant Cohorts
主要納入條件
Inclusion Criteria:
•At least 18 years of age.
•Participants must have histologically confirmed locally advanced, recurrent or metastatic solid tumor malignancies that cannot be treated with curative intent (surgery or radiotherapy).
•Participants must have progressed on or be intolerant of available standard of care treatment options or have disease for which there is no standard of care treatment available, with the exception of participants enrolling to the neoadjuvant cohorts.
•At least 2 lesions of measurable disease, unless specified otherwise in the selection criteria.
•Willingness to undergo biopsies.
•Demonstrated adequate organ function within 28 days of Cycle 1 Day 1 (C1D1).
•Life expectancy ＞12 weeks as determined by the Investigator.
•Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
•Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or antiCTLA 4 antibody must have at least 4 weeks from the last dose of antibody and evidence of disease progression per investigator assessment before enrollment.
•Participants who have previously received an immune checkpoint inhibitor prior to enrollment must have any immune related toxicities resolved to ≤Grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible.
•Female and male participants of childbearing potential who are sexually active must agree to use highly effective methods of contraception.
•At least 18 years of age.
•Participants must have histologically confirmed locally advanced, recurrent or metastatic solid tumor malignancies that cannot be treated with curative intent (surgery or radiotherapy).
•Participants must have progressed on or be intolerant of available standard of care treatment options or have disease for which there is no standard of care treatment available, with the exception of participants enrolling to the neoadjuvant cohorts.
•At least 2 lesions of measurable disease, unless specified otherwise in the selection criteria.
•Willingness to undergo biopsies.
•Demonstrated adequate organ function within 28 days of Cycle 1 Day 1 (C1D1).
•Life expectancy ＞12 weeks as determined by the Investigator.
•Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
•Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or antiCTLA 4 antibody must have at least 4 weeks from the last dose of antibody and evidence of disease progression per investigator assessment before enrollment.
•Participants who have previously received an immune checkpoint inhibitor prior to enrollment must have any immune related toxicities resolved to ≤Grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible.
•Female and male participants of childbearing potential who are sexually active must agree to use highly effective methods of contraception.
主要排除條件
Exclusion Criteria:
Participants who have been previously treated with a TLR agonist (excluding topical agents for unrelated disease) are not eligible.
Other active malignancies within the last 2 years are excluded.
Active autoimmune diseases, regardless of need for immunosuppressive treatment at the time of screening, with the exception of patients well controlled on physiologic endocrine replacement.
Systemic immunosuppressive treatment with the exception for patients on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation). Participants cannot start dosing on study until steroid dose is at or lower than 10 mg per day prednisone or equivalent.
Women who are breastfeeding or have a positive serum pregnancy test during screening or within 72 hours prior to C1D1 are not eligible.
Vaccination with live, attenuated vaccines within 4 weeks of enrollment.
Symptomatic central nervous system metastases.
Known bleeding disorder that is deemed to place the patient at unacceptable risk for bleeding complications from intratumoral injections or biopsies.
Known hypersensitivity to any component of TransCon TLR7/8 Agonist or pembrolizumab.
Any uncontrolled bacterial, fungal, viral, or other infection.
Treatment with any other anti-cancer systemic treatment (approved or investigational) or radiation therapy within 4 weeks of first dosing on study is not allowed.
Significant cardiac disease
A marked baseline prolongation of QT/QTc (corrected QT) interval (e.g., repeated demonstration of a QTc interval >480 ms (National Cancer Institute NCI) Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fredericia's QT correction formula.
A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, clinically significant hypokalemia, family history of Long QT Syndrome).
The use of concomitant medications that prolong the QT/QTc interval within 14 days of enrollment.
Positive for HIV or with active hepatitis B or C infection.
Participants who have been previously treated with a TLR agonist (excluding topical agents for unrelated disease) are not eligible.
Other active malignancies within the last 2 years are excluded.
Active autoimmune diseases, regardless of need for immunosuppressive treatment at the time of screening, with the exception of patients well controlled on physiologic endocrine replacement.
Systemic immunosuppressive treatment with the exception for patients on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation). Participants cannot start dosing on study until steroid dose is at or lower than 10 mg per day prednisone or equivalent.
Women who are breastfeeding or have a positive serum pregnancy test during screening or within 72 hours prior to C1D1 are not eligible.
Vaccination with live, attenuated vaccines within 4 weeks of enrollment.
Symptomatic central nervous system metastases.
Known bleeding disorder that is deemed to place the patient at unacceptable risk for bleeding complications from intratumoral injections or biopsies.
Known hypersensitivity to any component of TransCon TLR7/8 Agonist or pembrolizumab.
Any uncontrolled bacterial, fungal, viral, or other infection.
Treatment with any other anti-cancer systemic treatment (approved or investigational) or radiation therapy within 4 weeks of first dosing on study is not allowed.
Significant cardiac disease
A marked baseline prolongation of QT/QTc (corrected QT) interval (e.g., repeated demonstration of a QTc interval >480 ms (National Cancer Institute NCI) Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fredericia's QT correction formula.
A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, clinically significant hypokalemia, family history of Long QT Syndrome).
The use of concomitant medications that prolong the QT/QTc interval within 14 days of enrollment.
Positive for HIV or with active hepatitis B or C infection.
試驗計畫預計收納受試者人數
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台灣人數
30 人
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全球人數
220 人
