Design and preliminary report of a randomized phase IIb clinical trial of multitargeted recombinant adenovirus 5 vaccines against CEA, MUC1, and brachyury (Tri-Ad5) and the IL-15 receptor superagonist nogapendekin alfa inbakicept in Lynch syndrome (TRIAD5
Abstract
Lynch syndrome (LS) is a hereditary cancer syndrome that increases risk for colorectal and other cancers. We hypothesize that vaccines against tumor-associated antigens CEA, MUC1, and brachyury, simultaneously delivered in an adenovirus serotype-5 vector (Tri-Ad5) combined with the immune-enhancing IL-15 receptor superagonist nogapendekin-alfa-inbakicept (NAI) will reduce the incidence of colorectal neoplasms in LS carriers.
In this ongoing phase IIB double-blind placebo-controlled trial, two open-label safety phases (SPs) assessed safety of Tri-Ad5 alone (SP1, n=10) and with added NAI (SP2, n=10). A randomized controlled trial (RCT) follows the SPs. After baseline colonoscopy, vaccine dosing occurs at weeks 0, 4 and 8; Tri-Ad5 alone in SP1 and Tri-Ad5 plus NAI in SP2, with identical boosters at Week 52. The RCT phase participants (n=138) were randomized to receive Tri-Ad5 plus NAI or placebo. All participants complete colonoscopy at Weeks 52 and 104 for assessment of the primary endpoint: cumulative colorectal neoplasm incidence. Secondary endpoints include safety, tolerability, and immunogenicity.
All 20 SP participants (median age 57.5 (range 42-75), 70% female, 15% minority) received all prime and booster series. SP1 participants reported 139 adverse events (AEs) and SP2 participants reported 178. AEs were predominantly grade 1; no treatment-related serious adverse events (SAEs) occurred. The most common treatment-related AEs were reactogenic events including grade 3 rash (without skin necrosis or breakdown) at NAI injection site (100% of SP2 participants). The RCT phase (n=138) recently completed accrual.
In LS carriers without active cancer, the combination of Tri-Ad5 + NAI was well-tolerated; the RCT phase is ongoing.
https://clinicaltrials.gov/study/, identifier NCT05419011.
EDRN PI Authors
Medline Author List
- Aquila L
- Ballestar V
- Bansal A
- Barroilhet LM
- Bauman J
- Benante KA
- Bengtson L
- Boardman LA
- Brenner D
- Burke CA
- Della'Zanna G
- Djuric Z
- Donahue RN
- Eickhoff J
- Gabitzsch E
- Gulley JL
- Hall MJ
- Horn LA
- Hurley KE
- Hyun M
- Khan SA
- Lim R
- Madan R
- Moore DF
- Muller C
- Palena C
- Patel SG
- Richmond E
- Samaddar S
- Samadder NJ
- Schlom J
- Schuetze S
- Scott AJ
- Sender L
- Sharma P
- Singh A
- Soon-Shiong P
- Stanich PP
- Stoffel EM
- Szabo E
- Thompson P
- Toney NJ
- Umar A
- Vilar E
- Xu Y
- Zaborek J