Locally advanced or metastatic solid tumor malignancies MedDRA version: 21.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor Sys
Conditions
Interventions
Product Name: TransCon TLR7/8 Agonist
Product Code: ACP-017
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: TransCon TLR7/8 Agonist
Other descriptive name: ACP-017
Concentration uni
Sponsors
Ascendis Pharma Oncology Division A/S
Eligibility
Sex/Gender
All
Inclusion 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), 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: > 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 ;Secondary Objective: > 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;Primary 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 ;Timepoint(s) of evaluation of this end point: Through study completion, expected average of 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary 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;Timepoint(s) of evaluation of this end point: Average 2 years | — |
Countries
Australia, Georgia, Hungary, Korea, Republic of, Netherlands, Poland, Spain, Taiwan, United States
Contacts
Public ContactTranscon TLR Clinical
Ascendis Pharma Oncology Division A/S
Outcome results
None listed