A Study of TransCon TLR7/8 Agonist With or Without Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors

NCT ID: NCT04799054

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-18
• Study Completion Date: 2025-12-02

Brief Summary

TransCon TLR7/8 Agonist is an investigational drug being developed for treatment of locally advanced or metastatic solid tumors. This Phase 1/2 study will evaluate TransCon TLR7/8 Agonist as monotherapy or in combination with pembrolizumab in dose escalation and dose expansion. Participants will receive intratumoral (IT) injection of TransCon TLR7/8 Agonist every cycle. The primary objectives are to evaluate safety and tolerability, and define the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab.

Detailed Description

Toll-like receptors (TLRs) are a class of proteins that play a key role in innate immune cell recognition of foreign pathogens, stimulating innate and adaptive immune responses. TransCon TLR7/8 Agonist is designed as a long-acting localized delivery prodrug of resiquimod, a potent toll-like receptor (TLR) 7/8 agonist, with the potential to prolong high local concentrations of resiquimod and promote potent anti-tumoral responses while reducing systemic drug exposure and related adverse events. TransCon TLR7/8 Agonist is expected to stimulate innate and adaptive immune response in the tumor microenvironment and enhance the activity of checkpoint inhibitors like pembrolizumab.

Conditions

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)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

TransCon TLR7/8 Agonist

Intervention Type: DRUG

TransCon TLR7/8 Agonist will be administered as an IT injection

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.

Group Type: EXPERIMENTAL

TransCon TLR7/8 Agonist

Intervention Type: DRUG

TransCon TLR7/8 Agonist will be administered as an IT injection

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered IV

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.

Group Type: EXPERIMENTAL

TransCon TLR7/8 Agonist

Intervention Type: DRUG

TransCon TLR7/8 Agonist will be administered as an IT injection

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered IV

Interventions

TransCon TLR7/8 Agonist

TransCon TLR7/8 Agonist will be administered as an IT injection

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab will be administered IV

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ascendis Pharma Oncology Division A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joan Morris

Role: STUDY_DIRECTOR

Medical Monitor

Locations

Ascendis Pharma Investigational Site

Duarte, California, United States

Ascendis Investigational Site

Los Angeles, California, United States

Ascendis Investigational Site

Orange, California, United States

Ascendis Pharma Investigational Site

San Francisco, California, United States

Ascendis Investigational Site

Tampa, Florida, United States

Ascendis Pharma Investigational Site

Chicago, Illinois, United States

Ascendis Pharma Investigational Site

Iowa City, Iowa, United States

Ascendis Pharma Investigational Site

Louisville, Kentucky, United States

Ascendis Pharma Investigational Site

Canton, Ohio, United States

Ascendis Pharma Investigational Site

Cincinnati, Ohio, United States

Ascendis Pharma Investigational Site

Cleveland, Ohio, United States

Ascendis Pharma Investigational Site

Pittsburgh, Pennsylvania, United States

Ascendis Pharma Investigational Site

Knoxville, Tennessee, United States

Ascendis Investigational Site

Dallas, Texas, United States

Ascendis Investigational Site

Dallas, Texas, United States

Ascendis Investigational Site

Houston, Texas, United States

Ascendis Pharma Investigational Site

Fairfax, Virginia, United States

Ascendis Pharma Investigational Site

Wollongong, New South Wales, Australia

Ascendis Pharma Investigational Site

Frankston, Victoria, Australia

Ascendis Investigational Site

Bedford Park, , Australia

Ascendis Investigational Site

Amsterdam, , Netherlands

Ascendis Investigational Site

Rotterdam, , Netherlands

Ascendis Investigational Site

Dalseo-gu, , South Korea

Ascendis Investigational Site

Seocho-gu, , South Korea

Ascendis Investigational Site

Seogu, , South Korea

Ascendis Investigational Site

Seogu, , South Korea

Ascendis Investigational Site

Seongnam, , South Korea

Ascendis Investigational Site

Seoul, , South Korea

Ascendis Investigational Site

Seoul, , South Korea

Ascendis Investigational Site

Seoul, , South Korea

Ascendis Investigational Site

Suwon, , South Korea

Ascendis Investigational Site

Suwon, , South Korea

Ascendis Investigational Site

Barcelona, , Spain

Ascendis Investigational Site

Barcelona, , Spain

Ascendis Investigational Site

Barcelona, , Spain

Ascendis Investigational Site

Barcelona, , Spain

Ascendis Investigational Site

Madrid, , Spain

Ascendis Investigational Site

Madrid, , Spain

Ascendis Investigational Site

Madrid, , Spain

Ascendis Investigational Site

Madrid, , Spain

Ascendis Investigational Site

Málaga, , Spain

Ascendis Investigational Site

Murcia, , Spain

Ascendis Investigational Site

Pamplona, , Spain

Ascendis Investigational Site

Seville, , Spain

Ascendis Investigational Site

Valencia, , Spain

Ascendis Investigational Site

Taichung, , Taiwan

Ascendis Investigational Site

Taichung, , Taiwan

Ascendis Investigational Site

Tainan, , Taiwan

Ascendis Investigational Site

Taipei, , Taiwan

Countries

United States; Australia; Netherlands; South Korea; Spain; Taiwan

References

Lessmann T, Jones SA, Voigt T, Weisbrod S, Kracker O, Winter S, Zuniga LA, Stark S, Bisek N, Sprogoe K. Degradable Hydrogel for Sustained Localized Delivery of Anti-Tumor Drugs. J Pharm Sci. 2023 Nov;112(11):2843-2852. doi: 10.1016/j.xphs.2023.05.018. Epub 2023 Jun 4.

Reference Type: DERIVED

PMID: 37279836 (View on PubMed)

Zuniga LA, Lessmann T, Uppal K, Bisek N, Hong E, Rasmussen CE, Karlsson JJ, Zettler J, Holten-Andersen L, Bang K, Thakar D, Lee YC, Martinez S, Sabharwal SS, Stark S, Faltinger F, Kracker O, Weisbrod S, Muller R, Voigt T, Bigott K, Tabrizifard M, Breinholt VM, Mirza AM, Rosen DB, Sprogoe K, Punnonen J. Intratumoral delivery of TransCon TLR7/8 Agonist promotes sustained anti-tumor activity and local immune cell activation while minimizing systemic cytokine induction. Cancer Cell Int. 2022 Sep 19;22(1):286. doi: 10.1186/s12935-022-02708-6.

Reference Type: DERIVED

PMID: 36123697 (View on PubMed)

Other Identifiers

transcendIT-101

Identifier Type: OTHER

Identifier Source: secondary_id

TCTLR-101

Identifier Type: -

Identifier Source: org_study_id