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

April 10, 2026 updated by: Ascendis Pharma Oncology Division A/S

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
188

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Australia
      • Bedford Park, Australia, 5042
        • Ascendis Investigational Site
    • New South Wales
      • Wollongong, New South Wales, Australia, 2500
        • Ascendis Pharma Investigational Site
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Ascendis Pharma Investigational Site
  • Netherlands
      • Amsterdam, Netherlands, 1066
        • Ascendis Investigational Site
      • Rotterdam, Netherlands, 3015 GD
        • Ascendis Investigational Site
  • South Korea
      • Dalseo-gu, South Korea, 42601
        • Ascendis Investigational Site
      • Seocho-gu, South Korea, 06591
        • Ascendis Investigational Site
      • Seogu, South Korea, 49201
        • Ascendis Investigational Site
      • Seogu, South Korea, 49267
        • Ascendis Investigational Site
      • Seongnam, South Korea, 13620
        • Ascendis Investigational Site
      • Seoul, South Korea, 03722
        • Ascendis Investigational Site
      • Seoul, South Korea, 05505
        • Ascendis Investigational Site
      • Seoul, South Korea, 06273
        • Ascendis Investigational Site
      • Suwon, South Korea, 16247
        • Ascendis Investigational Site
      • Suwon, South Korea, 16499
        • Ascendis Investigational Site
  • Spain
      • Barcelona, Spain, 08003
        • Ascendis Investigational Site
      • Barcelona, Spain, 08028
        • Ascendis Investigational Site
      • Barcelona, Spain, 08035
        • Ascendis Investigational Site
      • Barcelona, Spain, 08908
        • Ascendis Investigational Site
      • Madrid, Spain, 28027
        • Ascendis Investigational Site
      • Madrid, Spain, 28040
        • Ascendis Investigational Site
      • Madrid, Spain, 28041
        • Ascendis Investigational Site
      • Madrid, Spain, 28050
        • Ascendis Investigational Site
      • Murcia, Spain, 30120
        • Ascendis Investigational Site
      • Málaga, Spain, 29010
        • Ascendis Investigational Site
      • Pamplona, Spain, 31008
        • Ascendis Investigational Site
      • Seville, Spain, 41009
        • Ascendis Investigational Site
      • Valencia, Spain, 46009
        • Ascendis Investigational Site
  • Taiwan
      • Taichung, Taiwan, 404
        • Ascendis Investigational Site
      • Taichung, Taiwan, 40705
        • Ascendis Investigational Site
      • Tainan, Taiwan, 704
        • Ascendis Investigational Site
      • Taipei, Taiwan, 112
        • Ascendis Investigational Site
  • United States
    • California
      • Duarte, California, United States, 91010
        • Ascendis Pharma Investigational Site
      • Los Angeles, California, United States, 90067
        • Ascendis Investigational Site
      • Orange, California, United States, 92868
        • Ascendis Investigational Site
      • San Francisco, California, United States, 94158
        • Ascendis Pharma Investigational Site
    • Florida
      • Tampa, Florida, United States, 33612
        • Ascendis Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Ascendis Pharma Investigational Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Ascendis Pharma Investigational Site
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Ascendis Pharma Investigational Site
    • Ohio
      • Canton, Ohio, United States, 44718
        • Ascendis Pharma Investigational Site
      • Cincinnati, Ohio, United States, 45219
        • Ascendis Pharma Investigational Site
      • Cleveland, Ohio, United States, 44106
        • Ascendis Pharma Investigational Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Ascendis Pharma Investigational Site
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Ascendis Pharma Investigational Site
    • Texas
      • Dallas, Texas, United States, 75235
        • Ascendis Investigational Site
      • Dallas, Texas, United States, 75390
        • Ascendis Investigational Site
      • Houston, Texas, United States, 77030
        • Ascendis Investigational Site
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Ascendis Pharma Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: TransCon TLR7/8 Agonist
TransCon TLR7/8 Agonist will be administered as an IT injection
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.
Drug: TransCon TLR7/8 Agonist
TransCon TLR7/8 Agonist will be administered as an IT injection
Drug: Pembrolizumab
Pembrolizumab will be administered IV
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.
Drug: TransCon TLR7/8 Agonist
TransCon TLR7/8 Agonist will be administered as an IT injection
Drug: Pembrolizumab
Pembrolizumab will be administered IV

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Through study completion, expected average of 2 years
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.
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)
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.
12 months
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
9 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to Response
Time Frame: Expected up to 1 year from first dose
Time from date of first dose of study treatment to first occurrence of response (CR or PR)
Expected up to 1 year from first dose
Overall Response Rate
Time Frame: Average of two years
Response assessed by RECIST v1.1 and itRECIST (response assessment for intratumoral immunotherapy for injected and noninjected lesions)
Average of two years
Duration of Response
Time Frame: Average of two years
Time from first documentation of objective tumor response (CR or PR that is subsequently confirmed) to first documentation of disease progression or death due to any cause, whichever occurs first
Average of two years
Progression Free Survival (PFS)
Time Frame: Average of two years
Time from date of first dose of study treatment to first documentation of disease progression or death due to any cause
Average of two years
Event free survival (EFS) by RECIST 1.1 per investigator assessment
Time Frame: Average of two years
Average of two years
Overall Survival (OS)
Time Frame: Average of two years
Time from date of first dose of study treatment to date of death due to any cause
Average of two years
PK characterization - Cmax
Time Frame: Average of two years
Maximum observed plasma concentration of resiquimod, O-desethyl resiquimod (metabolite) and total resiquimod (sum of bound and unbound resiquimod) after IT administration of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab
Average of two years
PK characterization - tmax
Time Frame: Average of two years
Time to reach maximum plasma concentration of resiquimod, O-desethyl resiquimod (metabolite) and total resiquimod (sum of bound and unbound resiquimod) after IT administration of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab
Average of two years
PK characterization - AUC0-t for first dose only
Time Frame: Average of two years
Area under the plasma concentration-time curve from time zero to last sampling time at which the concentration is at or above the lower limit of quantification for resiquimod, O-desethyl resiquimod (metabolite) and total resiquimod (sum of bound and unbound resiquimod) after IT administration of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab
Average of two years
PK characterization - t1/2
Time Frame: Average of two years
Apparent terminal half-life of resiquimod, O-desethyl resiquimod (metabolite) and total resiquimod (sum of bound and unbound resiquimod) after IT administration of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab
Average of two years
PK characterization - Ctrough
Time Frame: Average of two years
Plasma concentration immediately before next dosing of resiquimod, O-desethyl resiquimod (metabolite) and total resiquimod (sum of bound and unbound resiquimod) after IT administration of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab
Average of two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ascendis Pharma Oncology Division A/S

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Ascendis Oncology Clinical Trials, Ascendis Oncology Clinical Trials

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 18, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 2, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 2, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 26, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 16, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TCTLR-101
  • transcendIT-101 (Other Identifier: Ascendis Pharma)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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