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

NCT04799054 | Terminated Phase 1 FDA Drug

• 2 other identifiers: TCTLR-101transcendIT-101
• Study Type: interventional
• Target: 188
• Locations: 6 countries
• Sites: 49

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.

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)

Keywords

Ascendis Pharma; TransCon TLR7/8 Agonist; Locally Advanced Solid Tumor; Metastatic Solid Tumor; Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• 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

  Through study completion, expected average of 2 years

• 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.

  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)

  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

  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 Outcomes (11)

• Overall Response Rate

  Average of two years

• Duration of Response

  Average of two years

• Time to Response

  Expected up to 1 year from first dose

• Progression Free Survival (PFS)

  Average of two years

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

  Average of two years

Study Arms (3)

Part 1 Monotherapy Dose Escalation and Optimization: TransCon TLR7/8 Agonist

EXPERIMENTAL

TransCon TLR7/8 Agonist in escalating doses to evaluate safety/tolerability and to determine the MTD and RP2D.

Drug: TransCon TLR7/8 Agonist

Part 2 Combination Dose Escalation and Optimization: TransCon TLR7/8 Agonist with Pembrolizumab

EXPERIMENTAL

TransCon TLR7/8 Agonist with Pembrolizumab in escalating doses to evaluate safety/tolerability and determine the MTD and RP2D.

Drug: TransCon TLR7/8 Agonist; Drug: Pembrolizumab

Part 3 Phase 2 Combination Dose Expansion: TransCon TLR7/8 Agonist with Pembrolizumab

EXPERIMENTAL

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; Drug: Pembrolizumab

Interventions

TransCon TLR7/8 Agonist DRUG

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

Part 1 Monotherapy Dose Escalation and Optimization: TransCon TLR7/8 Agonist; Part 2 Combination Dose Escalation and Optimization: TransCon TLR7/8 Agonist with Pembrolizumab; Part 3 Phase 2 Combination Dose Expansion: TransCon TLR7/8 Agonist with Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab will be administered IV

Part 2 Combination Dose Escalation and Optimization: TransCon TLR7/8 Agonist with Pembrolizumab; Part 3 Phase 2 Combination Dose Expansion: TransCon TLR7/8 Agonist with Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ascendis Pharma Oncology Division A/S: lead

Study Sites (49)

Ascendis Pharma Investigational Site

Duarte, California, 91010, United States

Location

Ascendis Investigational Site

Los Angeles, California, 90067, United States

Location

Ascendis Investigational Site

Orange, California, 92868, United States

Location

Ascendis Pharma Investigational Site

San Francisco, California, 94158, United States

Location

Ascendis Investigational Site

Tampa, Florida, 33612, United States

Location

Ascendis Pharma Investigational Site

Chicago, Illinois, 60637, United States

Location

Ascendis Pharma Investigational Site

Iowa City, Iowa, 52242, United States

Location

Ascendis Pharma Investigational Site

Louisville, Kentucky, 40202, United States

Location

Ascendis Pharma Investigational Site

Canton, Ohio, 44718, United States

Location

Ascendis Pharma Investigational Site

Cincinnati, Ohio, 45219, United States

Location

Ascendis Pharma Investigational Site

Cleveland, Ohio, 44106, United States

Location

Ascendis Pharma Investigational Site

Pittsburgh, Pennsylvania, 15232, United States

Location

Ascendis Pharma Investigational Site

Knoxville, Tennessee, 37920, United States

Location

Ascendis Investigational Site

Dallas, Texas, 75235, United States

Location

Ascendis Investigational Site

Dallas, Texas, 75390, United States

Location

Ascendis Investigational Site

Houston, Texas, 77030, United States

Location

Ascendis Pharma Investigational Site

Fairfax, Virginia, 22031, United States

Location

Ascendis Pharma Investigational Site

Wollongong, New South Wales, 2500, Australia

Location

Ascendis Pharma Investigational Site

Frankston, Victoria, 3199, Australia

Location

Ascendis Investigational Site

Bedford Park, 5042, Australia

Location

Ascendis Investigational Site

Amsterdam, 1066, Netherlands

Location

Ascendis Investigational Site

Rotterdam, 3015 GD, Netherlands

Location

Ascendis Investigational Site

Dalseo-gu, 42601, South Korea

Location

Ascendis Investigational Site

Seocho-gu, 06591, South Korea

Location

Ascendis Investigational Site

Seogu, 49201, South Korea

Location

Ascendis Investigational Site

Seogu, 49267, South Korea

Location

Ascendis Investigational Site

Seongnam, 13620, South Korea

Location

Ascendis Investigational Site

Seoul, 03722, South Korea

Location

Ascendis Investigational Site

Seoul, 05505, South Korea

Location

Ascendis Investigational Site

Seoul, 06273, South Korea

Location

Ascendis Investigational Site

Suwon, 16247, South Korea

Location

Ascendis Investigational Site

Suwon, 16499, South Korea

Location

Ascendis Investigational Site

Barcelona, 08003, Spain

Location

Ascendis Investigational Site

Barcelona, 08028, Spain

Location

Ascendis Investigational Site

Barcelona, 08035, Spain

Location

Ascendis Investigational Site

Barcelona, 08908, Spain

Location

Ascendis Investigational Site

Madrid, 28027, Spain

Location

Ascendis Investigational Site

Madrid, 28040, Spain

Location

Ascendis Investigational Site

Madrid, 28041, Spain

Location

Ascendis Investigational Site

Madrid, 28050, Spain

Location

Ascendis Investigational Site

Málaga, 29010, Spain

Location

Ascendis Investigational Site

Murcia, 30120, Spain

Location

Ascendis Investigational Site

Pamplona, 31008, Spain

Location

Ascendis Investigational Site

Seville, 41009, Spain

Location

Ascendis Investigational Site

Valencia, 46009, Spain

Location

Ascendis Investigational Site

Taichung, 404, Taiwan

Location

Ascendis Investigational Site

Taichung, 40705, Taiwan

Location

Ascendis Investigational Site

Tainan, 704, Taiwan

Location

Ascendis Investigational Site

Taipei, 112, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 37279836 DERIVED

• 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.

  PMID: 36123697 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ascendis Oncology Clinical Trials

  Ascendis Oncology Clinical Trials

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: March 16, 2021
• Study Start: March 18, 2021
• Primary Completion: December 2, 2025
• Study Completion: December 2, 2025
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); ES (13); AU (3); US (17); KR (10); TW (4)