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Summary
EudraCT Number:2021-001403-33
Sponsor's Protocol Code Number:TCTLR-101
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2023-02-09
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2021-001403-33
A.3Full title of the trial
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
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
A Study of TransCon TLR7/8 Agonist With or Without Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors
A.3.2Name or abbreviated title of the trial where available
transcendIT-101
A.4.1Sponsor's protocol code numberTCTLR-101
A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04799054
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorAscendis Pharma Oncology Division A/S
B.1.3.4CountryDenmark
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportAscendis Pharma Oncology Division A/S
B.4.2CountryDenmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationAscendis Pharma Oncology Division A/S
B.5.2Functional name of contact pointTranscon TLR Clinical
B.5.3 Address:
B.5.3.1Street AddressTuborg Boulevard 12
B.5.3.2Town/ cityHellerup
B.5.3.3Post code2900
B.5.3.4CountryDenmark
B.5.4Telephone number+4570222244
B.5.6E-mailclinhelpdesk@ascendispharma.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameTransCon TLR7/8 Agonist
D.3.2Product code ACP-017
D.3.4Pharmaceutical form Suspension for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntratumoral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNTransCon TLR7/8 Agonist
D.3.9.3Other descriptive nameACP-017
D.3.9.4EV Substance CodeSUB224151
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number0.5
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name KEYTRUDA 25 mg/mL concentrate for solution for infusion
D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIn vitro use (Noncurrent)
Intrauterine use
Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNPembrolizumab
D.3.9.1CAS number 1374853-91-4
D.3.9.4EV Substance CodeSUB167136
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number25
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Locally advanced or metastatic solid tumor malignancies
E.1.1.1Medical condition in easily understood language
Cancer
E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.0
E.1.2Level LLT
E.1.2Classification code 10049280
E.1.2Term Solid tumour
E.1.2System Organ Class 100000004864
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level LLT
E.1.2Classification code 10065143
E.1.2Term Malignant solid tumour
E.1.2System Organ Class 100000004864
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level LLT
E.1.2Classification code 10065147
E.1.2Term Malignant solid tumor
E.1.2System Organ Class 100000004864
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level LLT
E.1.2Classification code 10065252
E.1.2Term Solid tumor
E.1.2System Organ Class 100000004864
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
> To evaluate the 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
> Part 3 Neoadjuvant Cohorts (Cohorts 3c and 3d): To evaluate the anti-tumor activity of TransCon TLR7/8 Agonist in combination with pembrolizumab
E.2.2Secondary objectives of the trial
> To evaluate the anti-tumor activity of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab
> To characterize the plasma pharmacokinetics (PK) of resiquimod, O-desethyl resiquimod, and total resiquimod (unbound + bound) after IT administration of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab
E.2.3Trial contains a sub-study No
E.3Principal 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), with the exception of participants enrolling to the neoadjuvant cohorts.
•Participants must have progressed on or be intolerant of available SOC treatment options or have disease for which there is no SOC 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 anti CTLA 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.
E.4Principal 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.
E.5 End points
E.5.1Primary end point(s)
> All Parts: Incidence and severity of serious adverse events and adverse events
> Parts 1 and 2 Dose Escalation Cohorts: Incidence of dose limiting toxicities (DLTs)
> Part 3 Neoadjuvant Cohorts (Cohorts 3c and 3d): Pathologic complete response (pCR) per local assessment for pathology review


E.5.1.1Timepoint(s) of evaluation of this end point
Through study completion, expected average of 2 years
E.5.2Secondary end point(s)
> Parts 1 and 2, and Part 3 HNSCC and other HPV-associated tumor types Cohorts (Cohorts 3a and 3b):
- Objective response rate (ORR) by RECIST 1.1, duration of response (DoR) and TTR (time to response) per independent central review (ICR)
- ORR by RECIST 1.1, DoR and TTR per investigator assessment
- ORR for overall tumor burden, injected and noninjected lesions by itRECIST, DoR, and TTR per investigator assessment
- Progression free survival (PFS) by RECIST 1.1 per ICR
- PFS by RECIST 1.1 per investigator assessment
- Overall survival (OS)
> Part 3 Neoadjuvant Cohorts (Cohorts 3c and 3d):
- pCR per central assessment for pathology review
- Major pathologic response (MPR) per local assessment for pathology review
- MPR per central assessment for pathology review
- Event free survival (EFS) by RECIST 1.1 per investigator assessment
- OS
> TransCon TLR7/8 Agonist PK parameters
E.5.2.1Timepoint(s) of evaluation of this end point
Average 2 years
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic Yes
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) Yes
E.7.1.1First administration to humans Yes
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned2
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA23
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Taiwan
Australia
Georgia
Korea, Republic of
United States
Hungary
Netherlands
Poland
Spain
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
The end of treatment for a participant is the date of the last study treatment administration. The End of Study visit for a participant will be performed 28 days (±7 days) after the last study treatment administration. The end of study is defined as the time of last contact with the last participant enrolled into the study for collection of last data point required for statistical analysis or the Sponsor decides to end the trial, whichever occurs first.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years4
E.8.9.1In the Member State concerned months8
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years4
E.8.9.2In all countries concerned by the trial months8
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 110
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 110
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state13
F.4.2 For a multinational trial
F.4.2.1In the EEA 77
F.4.2.2In the whole clinical trial 220
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Expected normal treatment of that condition
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-02-09
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2023-04-28
P. End of Trial
P.End of Trial StatusOngoing

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