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Advanced Solid TumorPhase 1/2NCT04799054

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

A Phase 1/2 study testing TransCon TLR7/8 Agonist and Pembrolizumab in people with Advanced Solid Tumor and Locally Advanced Solid Tumor, run by Ascendis Pharma Oncology Division A/S at 49 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TransCon TLR7/8 Agonist and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
188 participants
Where
49 sitesin 6 countries
Study dates
18 Mar 2021to 2 Dec 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.

Trial locations and contacts

49 sites in 6 countries.

49 sites in 6 countries

United States17 sites

  • Ascendis Pharma Investigational Site

    Canton, Ohio, 44718

  • Ascendis Pharma Investigational Site

    Chicago, Illinois, 60637

  • Ascendis Pharma Investigational Site

    Cincinnati, Ohio, 45219

  • Ascendis Pharma Investigational Site

    Cleveland, Ohio, 44106

  • Ascendis Investigational Site

    Dallas, Texas, 75235

  • Ascendis Investigational Site

    Dallas, Texas, 75390

  • Ascendis Pharma Investigational Site

    Duarte, California, 91010

  • Ascendis Pharma Investigational Site

    Fairfax, Virginia, 22031

  • Ascendis Investigational Site

    Houston, Texas, 77030

  • Ascendis Pharma Investigational Site

    Iowa City, Iowa, 52242

  • Ascendis Pharma Investigational Site

    Knoxville, Tennessee, 37920

  • Ascendis Investigational Site

    Los Angeles, California, 90067

  • Ascendis Pharma Investigational Site

    Louisville, Kentucky, 40202

  • Ascendis Investigational Site

    Orange, California, 92868

  • Ascendis Pharma Investigational Site

    Pittsburgh, Pennsylvania, 15232

  • Ascendis Pharma Investigational Site

    San Francisco, California, 94158

  • Ascendis Investigational Site

    Tampa, Florida, 33612

Other trials in United States

Spain13 sites

  • Ascendis Investigational Site

    Barcelona, 08003

  • Ascendis Investigational Site

    Barcelona, 08028

  • Ascendis Investigational Site

    Barcelona, 08035

  • Ascendis Investigational Site

    Barcelona, 08908

  • Ascendis Investigational Site

    Madrid, 28027

  • Ascendis Investigational Site

    Madrid, 28040

  • Ascendis Investigational Site

    Madrid, 28041

  • Ascendis Investigational Site

    Madrid, 28050

  • Ascendis Investigational Site

    Málaga, 29010

  • Ascendis Investigational Site

    Murcia, 30120

  • Ascendis Investigational Site

    Pamplona, 31008

  • Ascendis Investigational Site

    Seville, 41009

  • Ascendis Investigational Site

    Valencia, 46009

Other trials in Spain

South Korea10 sites

  • Ascendis Investigational Site

    Dalseo-gu, 42601

  • Ascendis Investigational Site

    Seocho-gu, 06591

  • Ascendis Investigational Site

    Seogu, 49201

  • Ascendis Investigational Site

    Seogu, 49267

  • Ascendis Investigational Site

    Seongnam, 13620

  • Ascendis Investigational Site

    Seoul, 03722

  • Ascendis Investigational Site

    Seoul, 05505

  • Ascendis Investigational Site

    Seoul, 06273

  • Ascendis Investigational Site

    Suwon, 16247

  • Ascendis Investigational Site

    Suwon, 16499

Other trials in South Korea

Taiwan4 sites

  • Ascendis Investigational Site

    Taichung, 404

  • Ascendis Investigational Site

    Taichung, 40705

  • Ascendis Investigational Site

    Tainan, 704

  • Ascendis Investigational Site

    Taipei, 112

Other trials in Taiwan

Australia3 sites

  • Ascendis Investigational Site

    Bedford Park, 5042

  • Ascendis Pharma Investigational Site

    Frankston, Victoria, 3199

  • Ascendis Pharma Investigational Site

    Wollongong, New South Wales, 2500

Other trials in Australia

Netherlands2 sites

  • Ascendis Investigational Site

    Amsterdam, 1066

  • Ascendis Investigational Site

    Rotterdam, 3015 GD

Other trials in Netherlands

About this study

Official title: 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.

Read the 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.

Being tested
TransCon TLR7/8 Agonist, Pembrolizumab
Keywords
Ascendis Pharma, TransCon TLR7/8 Agonist, Locally Advanced Solid Tumor, Metastatic Solid Tumor, Advanced Solid Tumor
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TransCon TLR7/8 AgonistDrug

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

  • PembrolizumabDrug

    Pembrolizumab will be administered IV

Study groups in NCT04799054
Study groupRoleWhat they receive
Part 1 Monotherapy Dose Escalation and Optimization: TransCon TLR7/8 AgonistExperimentalTransCon TLR7/8 Agonist in escalating doses to evaluate safety/tolerability and to determine the MTD and RP2D.
Receives: Drug: TransCon TLR7/8 Agonist
Part 2 Combination Dose Escalation and Optimization: TransCon TLR7/8 Agonist with PembrolizumabExperimentalTransCon TLR7/8 Agonist with Pembrolizumab in escalating doses to evaluate safety/tolerability and determine the MTD and RP2D.
Receives: Drug: TransCon TLR7/8 Agonist; Drug: Pembrolizumab
Part 3 Phase 2 Combination Dose Expansion: TransCon TLR7/8 Agonist with PembrolizumabExperimentalTransCon 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.
Receives: Drug: TransCon TLR7/8 Agonist; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and Tolerability

    Treatment emergent and treatment related adverse events (assessed by CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, deaths

    Measured: Through study completion, expected average of 2 years

  2. Maximum Tolerated Dose (MTD)

    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.

    Measured: 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)

  3. Recommended Phase 2 Dose (RP2D)

    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.

    Measured: 12 months

  4. Response

    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

    Measured: 9 weeks

Secondary outcomes (11)

  1. Overall Response Rate

    Response assessed by RECIST v1.1 and itRECIST (response assessment for intratumoral immunotherapy for injected and noninjected lesions)

    Measured: Average of two years

  2. Duration of Response

    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

    Measured: Average of two years

  3. Time to Response

    Time from date of first dose of study treatment to first occurrence of response (CR or PR)

    Measured: Expected up to 1 year from first dose

  4. Progression Free Survival (PFS)

    Time from date of first dose of study treatment to first documentation of disease progression or death due to any cause

    Measured: Average of two years

  5. Event free survival (EFS) by RECIST 1.1 per investigator assessment

    Measured: Average of two years

  6. Overall Survival (OS)

    Time from date of first dose of study treatment to date of death due to any cause

    Measured: Average of two years

  7. PK characterization - Cmax

    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

    Measured: Average of two years

  8. PK characterization - tmax

    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

    Measured: Average of two years

  9. PK characterization - AUC0-t for first dose only

    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

    Measured: Average of two years

  10. PK characterization - t1/2

    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

    Measured: Average of two years

  11. PK characterization - Ctrough

    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

    Measured: Average of two years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2021
  2. Study start18 Mar 2021
  3. Primary completion2 Dec 2025
  4. Study completion2 Dec 2025

Why it stopped: The Sponsor made the decision to close enrollment to prioritize our efforts on TransCon IL-2 ß/g.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
188 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04799054
Sponsor's protocol ID
TCTLR-101
Other IDs
transcendIT-101
Status last verified
Apr 2026
First submitted
26 Feb 2021
Last updated
13 Apr 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37279836

  • 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.

    PubMed 36123697

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TransCon TLR7/8 Agonist and Pembrolizumab in people with Advanced Solid Tumor and Locally Advanced Solid Tumor, run by Ascendis Pharma Oncology Division A/S at 49 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, Spain, South Korea, Taiwan, Australia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The Sponsor made the decision to close enrollment to prioritize our efforts on TransCon IL-2 ß/g.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability (time frame: Through study completion, expected average of 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04799054, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.

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Clinical Trial NCT04799054 | AzTrials