Trial Title:
TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma
NCT ID:
NCT05980598
Condition:
Head and Neck Neoplasms
Conditions: Official terms:
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Head and Neck Neoplasms
Pembrolizumab
Conditions: Keywords:
HNSCC
Head and Neck Cancer
TransCon TLR7/8 Agonist
TC TLR7/8
TransCon IL-2 β/γ
TC IL-2 β/γ
Neoadjuvant
Neoadjuvant Head and Neck
LA-HNSCC
Locoregionally Advanced HNSCC
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
TransCon TLR7/8 Agonist
Description:
TLR7/8 agonist prodrug
Arm group label:
TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ
Arm group label:
TransCon TLR7/8 Agonist in combination with pembrolizumab
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
A type of immunotherapy that works by blocking the PD-1 pathway to help prevent cancer
cells from hiding
Arm group label:
Pembrolizumab
Arm group label:
TransCon TLR7/8 Agonist in combination with pembrolizumab
Other name:
Keytruda™
Intervention type:
Drug
Intervention name:
TransCon IL-2 β/γ
Description:
Sustained systemic release of IL-2 β/γ with selective receptor binding that may stimulate
the immune system to kill cancer cells
Arm group label:
TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ
Summary:
The purpose of this trial is to evaluate the safety and efficacy of TransCon TLR7/8
Agonist, TransCon IL-2 β/γ, and pembrolizumab given prior to curative intent surgery in
treatment of participants with newly diagnosed Stage III/IVA resectable locoregionally
advanced head and neck squamous cell carcinoma (LA-HNSCC). After surgery, participants
will receive local standard-of-care treatment and will be followed for safety, efficacy,
and survival for up to 2 years.
This trial contains a safety run-in to evaluate the safety and tolerability of the two
treatment arms: Arm A (TransCon TLR7/8 Agonist plus pembrolizumab) and Arm B (TransCon
TLR7/8 Agonist plus TransCon IL-2 β/γ). The safety run-in will be followed by the
randomized Phase 2, open-label part of the trial comparing the safety, efficacy and
survival of treatment Arm A or Arm B compared to treatment Arm C (pembrolizumab
monotherapy).
Detailed description:
This is a randomized, Phase 2, open-label, multicenter trial of TransCon TLR7/8 Agonist
in combination with pembrolizumab, TransCon TLR7/8 Agonist in combination with TransCon
IL-2 β/γ, or pembrolizumab monotherapy as neoadjuvant therapy in participants with Stage
III-IVA resectable LA-HNSCC.
This trial starts with a safety run-in of 12 participants, 6 participants each in Arms A
(TransCon TLR7/8 Agonist plus pembrolizumab) and B (TransCon TLR7/8 Agonist plus TransCon
IL-2 β/γ) randomized 1:1.
After completing the safety run-in, 80 participants will be randomized in a 2:2:1 ratio
in 3 treatment Arms A, B or C (pembrolizumab monotherapy).
Once randomized, participants should begin treatment within 5 calendar days. Participants
enrolled after the safety run-in, into the 2:2:1 randomization part of the trial, will be
stratified as follows: oropharyngeal HPV p16 positive versus oropharyngeal HPV p16
negative or larynx/hypopharyngeal/oral cavity regardless of HPV p16 status. All
participants should receive study drug(s) every 21 days (Q21D) for 2 cycles followed by
curative-intent surgery. After surgery, participants may receive standard-of-care
treatment in the adjuvant setting, as per investigator's decision and local guidelines.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Has local histologically confirmed new diagnosis of resectable, non-metastatic, SCC
that is either: Stage III tumor HPV-positive oropharyngeal primary that is tumor
size (T) 4, lymph node involvement (N) 0-2, no distant metastases (M) 0; Stage III
or IVA oropharyngeal tumor HPV-negative; or Stage III or IVA larynx/hypopharynx/oral
cavity primaries regardless of HPV status (per American Joint Committee on Cancer
[AJCC] Staging, 8th edition).
- Has available archived or fresh core or excisional biopsy of a tumor lesion. Note:
Fine needle aspirations may be allowed after discussion with Medical Monitor.
- Is eligible and plans for primary LA-HNSCC surgery based on investigator decision
and per local practice.
- Has results from tumor HPV status by p16 immunohistochemistry (IHC) for
oropharyngeal tumors. (HPV DNA analysis for HPV tumor status is acceptable if that
is the local standard of care analysis.)
- Has adequate organ function at screening.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Has at least one lesion that is deemed by the investigator to be easily and safely
accessible for IT injection.
Exclusion Criteria:
- Active autoimmune conditions.
- Has significant cardiac disease.
- Has a known bleeding disorder that is deemed to place the participant at
unacceptable risk for bleeding complications from IT injections or biopsies.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in
doses exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to randomization.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Los Angeles
Zip:
90067
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
San Francisco
Zip:
94158
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Chicago
Zip:
60612
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Louisville
Zip:
40202
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
New York
Zip:
11794
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Pharma Investigational Site
Address:
City:
Canton
Zip:
44718
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Cincinnati
Zip:
45219
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Charleston
Zip:
29425
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Knoxville
Zip:
37902
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Kutaisi
Zip:
4600
Country:
Georgia
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Tbilisi
Zip:
0114
Country:
Georgia
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Tbilisi
Zip:
0144
Country:
Georgia
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site II
Address:
City:
Tbilisi
Zip:
0159
Country:
Georgia
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Tbilisi
Zip:
0159
Country:
Georgia
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Tbilisi
Zip:
0186
Country:
Georgia
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Erlangen
Zip:
91054
Country:
Germany
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Jena
Zip:
07747
Country:
Germany
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Mannheim
Zip:
68167
Country:
Germany
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Pécs
Zip:
7624
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Budapest
Zip:
1122
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Debrecen
Zip:
4032
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Győr
Zip:
9024
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Zalaegerszeg
Zip:
8900
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Milan
Zip:
20133
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Milan
Zip:
20141
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Modena
Zip:
41125
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Naples
Zip:
80131
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Novara
Zip:
28100
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Pavia
Zip:
27100
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Rozzano
Zip:
20089
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Gliwice
Zip:
44-102
Country:
Poland
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Siedlce
Zip:
08-110
Country:
Poland
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Warszawa
Zip:
02-781
Country:
Poland
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Barcelona
Zip:
08003
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
El Palmar
Zip:
30120
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
L'Hospitalet De Llobregat
Zip:
08908
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Lugo
Zip:
27003
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Madrid
Zip:
28027
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site II
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Málaga
Zip:
29011
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Pamplona
Zip:
31008
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Terrassa
Zip:
08221
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Valencia
Zip:
46009
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Valencia
Zip:
46014
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Valencia
Zip:
46026
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Zaragoza
Zip:
50009
Country:
Spain
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Kaohsiung City
Zip:
80708
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Kaohsiung City
Zip:
83301
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Taichung
Zip:
404
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Tainan
Zip:
70456
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Ascendis Investigational Site
Address:
City:
Taoyuan
Zip:
333
Country:
Taiwan
Status:
Recruiting
Start date:
September 29, 2023
Completion date:
July 30, 2027
Lead sponsor:
Agency:
Ascendis Pharma A/S
Agency class:
Industry
Source:
Ascendis Pharma A/S
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05980598
