Clinical Trials List
Protocol NumberTCTLR-101
NCT Number(ClinicalTrials.gov Identfier)NCT04799054
2022-11-30 - 2027-03-31
Phase I/II
Recruiting4
Phase 1/2, Open-label, Dose Escalation and Dose Expansion Study of TransCon TLR7/8 Agonist Alone or in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumor Malignancies
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Trial Applicant
WORLDWIDE CLINICAL TRIALS (TAIWAN) CO., LTD.
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Sponsor
-
Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Tsung-Lun Lee 無
- 戴世光 無
- 朱本元 無
- Tien-Hua Chen 無
- Mu-Hsin Chang 無
- Chia-Fan Chang 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 趙勇全 無
- CHENG-HSIEN LIN 無
- 陳建志 無
- ZHENG-WEI ZHOU 無
- 李權 無
- Chen-Chi Wang 無
- 鄭皓升 無
- 林玟君 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Advanced Solid Tumor、Locally Advanced Solid Tumor、Metastatic Solid Tumor、Head and Neck Squamous Cell Carcinoma HNSCC、HPV-associated Cancers、Neoadjuvant Melanoma 、Neoadjuvant Cutaneous Squamous Cell Carcinoma (cSCC)
Objectives
Experimental: Part 1 Monotherapy Dose Escalation and Optimization: TransCon TLR7/8 Agonist
TransCon TLR7/8 Agonist in escalating doses to evaluate safety/tolerability and to determine the MTD and RP2D.
Experimental: Part 2 Combination Dose Escalation and Optimization: TransCon TLR7/8 Agonist with Pembrolizumab
TransCon TLR7/8 Agonist with Pembrolizumab in escalating doses to evaluate safety/tolerability and determine the MTD and RP2D.
Experimental: Part 3 Phase 2 Combination Dose Expansion: TransCon TLR7/8 Agonist with Pembrolizumab
TransCon TLR7/8 Agonist with Pembrolizumab using RP2D from Part 2 to evaluate safety/tolerability and anti-tumor activity of the combination in indication-specific dose expansion cohorts.
Test Drug
TransCon TLR7/8 Agonist (ACP-017)KEYTRUDA
Active Ingredient
TransCon TLR7/8 Agonist
Pembrolizumab
Pembrolizumab
Dosage Form
Injection
Injection
Injection
Dosage
0.5mg/mL
100mg/4mL
100mg/4mL
Endpoints
Main outcome measures:
1. Safety and tolerability [Time frame: until trial completion, expected average of 2 years]
- Treatment-emergent and treatment-related adverse events (assessed according to CTCAE version 5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, and deaths
2. Maximum Tolerated Dose (MTD) [Time frame: Cycle 1 of Part 1 (monotherapy dose escalation) (each cycle is 21 days) and Cycle 1 of Part 2 (combination therapy dose escalation) (the first cycle is 28 days and 21 days)]
- The maximum tolerated dose was determined by evaluating the incidence of dose-limiting toxicities (DLTs), treatment-emergent and treatment-related adverse events (assessed according to CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, and deaths.
3. Phase 2 recommended dose (RP2D) [Time frame: 12 months]
- The recommended Phase 2 dose of TransCon TLR7/8 agonist and combination therapy for further development will be determined by evaluating the number of patients experiencing treatment-related adverse events assessed by CTCAE.
4. Response [Time frame: 9 weeks]
- Pathological complete response (pCR) based on pathological review of anti-tumor activity of TransCon TLR7/8 Agonist plus pembrolizumab in the neoadjuvant arm, as assessed by local assessment
Secondary outcome measures:
1. Overall response rate [Time frame: average two years]
- Response assessed according to RECIST version 1.1 and itRECIST (assessment of intratumoral immunotherapy response in injected and non-injected lesions)
2. Duration of response [Time frame: average two years]
- Time from first documented objective tumor response (subsequently confirmed CR or PR) to first documented disease progression or death from any cause, whichever occurred first
3. Response time [Time frame: expected to be up to 1 year from the first dose]
- Time from date of first dose of trial treatment to first response (CR or PR)
4. Progression-free survival (PFS) [Time frame: average two years]
- Time from the date of the first dose of trial treatment to the first documented disease progression or death from any cause
5. Event-free survival (EFS) assessed by the trial sponsor according to RECIST 1.1 [Time frame: average of two years]
6. Overall survival (OS) [Time frame: average two years]
- Time from the date of the first dose of trial treatment to the date of death from any cause
7. PK properties - Cmax [Time frame: two-year average]
-Maximum Observed Plasma Concentrations of resiquimod, O-desethyl resiquimod (metabolite), and resiquimod (sum of bound and unbound resiquimod) following IT administration of TransCon TLR7/8 Agonist monotherapy or concomitantly with pembrolizumab
8. PK properties - tmax [Time frame: two-year average]
- Time to maximum plasma concentrations of resiquimod, O-desethyl resiquimod (metabolite), and resiquimod (total bound and unbound resiquimod) following IT administration of TransCon TLR7/8 Agonist monotherapy or concomitantly with pembrolizumab
9. PK properties - AUC0-t for first dose only [Time frame: two-year average]
- Area under the plasma concentration-time curve from time zero to the last sampling time at concentrations equal to or above the lower limit of quantitation for resiquimod, O-desethyl resiquimod (metabolite), and total resiquimod (sum of bound and unbound resiquimod) following IT administration of TransCon TLR7/8 Agonist as a single agent or in combination with pembrolizumab
10. PK properties - t1/2 [Time frame: two-year average]
- Apparent terminal half-lives of resiquimod, O-desethyl resiquimod (metabolite), and resiquimod (sum of bound and unbound resiquimod) following IT administration of TransCon TLR7/8 agonists alone or in combination with pembrolizumab
11. PK characteristics - Ctrough [Time frame: average two years]
- Plasma concentrations of TransCon TLR7/8 Agonist administered IT alone or in combination with pembrolizumab immediately before the next dose of resiquimod, O-desethyl resiquimod (metabolite), and resiquimod (sum of bound and unbound resiquimod)
1. Safety and tolerability [Time frame: until trial completion, expected average of 2 years]
- Treatment-emergent and treatment-related adverse events (assessed according to CTCAE version 5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, and deaths
2. Maximum Tolerated Dose (MTD) [Time frame: Cycle 1 of Part 1 (monotherapy dose escalation) (each cycle is 21 days) and Cycle 1 of Part 2 (combination therapy dose escalation) (the first cycle is 28 days and 21 days)]
- The maximum tolerated dose was determined by evaluating the incidence of dose-limiting toxicities (DLTs), treatment-emergent and treatment-related adverse events (assessed according to CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, and deaths.
3. Phase 2 recommended dose (RP2D) [Time frame: 12 months]
- The recommended Phase 2 dose of TransCon TLR7/8 agonist and combination therapy for further development will be determined by evaluating the number of patients experiencing treatment-related adverse events assessed by CTCAE.
4. Response [Time frame: 9 weeks]
- Pathological complete response (pCR) based on pathological review of anti-tumor activity of TransCon TLR7/8 Agonist plus pembrolizumab in the neoadjuvant arm, as assessed by local assessment
Secondary outcome measures:
1. Overall response rate [Time frame: average two years]
- Response assessed according to RECIST version 1.1 and itRECIST (assessment of intratumoral immunotherapy response in injected and non-injected lesions)
2. Duration of response [Time frame: average two years]
- Time from first documented objective tumor response (subsequently confirmed CR or PR) to first documented disease progression or death from any cause, whichever occurred first
3. Response time [Time frame: expected to be up to 1 year from the first dose]
- Time from date of first dose of trial treatment to first response (CR or PR)
4. Progression-free survival (PFS) [Time frame: average two years]
- Time from the date of the first dose of trial treatment to the first documented disease progression or death from any cause
5. Event-free survival (EFS) assessed by the trial sponsor according to RECIST 1.1 [Time frame: average of two years]
6. Overall survival (OS) [Time frame: average two years]
- Time from the date of the first dose of trial treatment to the date of death from any cause
7. PK properties - Cmax [Time frame: two-year average]
-Maximum Observed Plasma Concentrations of resiquimod, O-desethyl resiquimod (metabolite), and resiquimod (sum of bound and unbound resiquimod) following IT administration of TransCon TLR7/8 Agonist monotherapy or concomitantly with pembrolizumab
8. PK properties - tmax [Time frame: two-year average]
- Time to maximum plasma concentrations of resiquimod, O-desethyl resiquimod (metabolite), and resiquimod (total bound and unbound resiquimod) following IT administration of TransCon TLR7/8 Agonist monotherapy or concomitantly with pembrolizumab
9. PK properties - AUC0-t for first dose only [Time frame: two-year average]
- Area under the plasma concentration-time curve from time zero to the last sampling time at concentrations equal to or above the lower limit of quantitation for resiquimod, O-desethyl resiquimod (metabolite), and total resiquimod (sum of bound and unbound resiquimod) following IT administration of TransCon TLR7/8 Agonist as a single agent or in combination with pembrolizumab
10. PK properties - t1/2 [Time frame: two-year average]
- Apparent terminal half-lives of resiquimod, O-desethyl resiquimod (metabolite), and resiquimod (sum of bound and unbound resiquimod) following IT administration of TransCon TLR7/8 agonists alone or in combination with pembrolizumab
11. PK characteristics - Ctrough [Time frame: average two years]
- Plasma concentrations of TransCon TLR7/8 Agonist administered IT alone or in combination with pembrolizumab immediately before the next dose of resiquimod, O-desethyl resiquimod (metabolite), and resiquimod (sum of bound and unbound resiquimod)
Inclution 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.
‧ 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.
Exclusion Criteria
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.
The Estimated Number of Participants
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Taiwan
30 participants
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Global
220 participants
