Jack Shuang Hou, Scientific Director at Jtests, shared on LinkedIn:
“BioNTech SE and OncoC4, Inc.’s Gotistobart Nearly Doubles Median Survival vs Docetaxel in Previously Treated Squamous NSCLC
Updated WCLC26 data from Stage 1 of the Phase III PRESERVE-003 trial show gotistobart (BNT316/ONC-392) delivering a major survival signal in patients whose disease progressed after immunotherapy and chemotherapy.
18.5-Month Median Overall Survival
Among 87 patients:
- Gotistobart: 18.5 months OS
- Docetaxel: 10.0 months
44% reduction in risk of death
HR 0.56; nominal p=0.0295
This is particularly notable in a setting where current median survival is typically <1 year.
Grade ≥3 treatment-related AEs were 44.4% vs 48.8% with docetaxel.
A Different Approach to CTLA-4
Gotistobart is a pH-sensitive CTLA-4-targeting antibody designed to selectively enhance regulatory T-cell depletion within the tumor microenvironment.
The concept: Treg depletion – re-engage suppressed anti-tumor immunity – potentially overcome acquired resistance after PD-(L)1 therapy.
Unlike conventional CTLA-4 approaches, its design enables CTLA-4 recycling, aiming to preserve peripheral immune checkpoint function while enhancing activity within tumors.
Pivotal Global Validation Underway
These results come from the non-pivotal Stage 1 cohort of PRESERVE-003.
The pivotal Stage 2 is now ongoing across 160+ global sites, with overall survival as the primary endpoint.
Gotistobart previously received FDA Fast Track Designation and Orphan Drug Designation for squamous NSCLC.
Leadership Perspective
Özlem Türeci, Co-Founder and CMO of BioNTech SE, highlighted the potential to re-engage exhausted anti-tumor immunity after resistance to initial therapy.
My Takeaway
This is an intriguing example of next-generation checkpoint engineering.
Rather than abandoning immunotherapy after PD-(L)1 resistance, gotistobart attempts to reprogram the tumor immune environment through selective CTLA-4/Treg modulation.
An 18.5 vs 10.0-month OS signal is impressive-but Stage 2 will be the critical test.
If reproduced globally, this could challenge chemotherapy’s long-standing role after immunotherapy failure in squamous NSCLC.”
This also can be interesting:
PRESERVE-003: Gotistobart Improves Survival in sqNSCLC After PD-(L)1 Failure
