2025 Highlights at a Glance
| Advance | Significance |
|---|---|
| VT3989 TEAD inhibitor | 40-week PFS, FDA Fast Track |
| BNT327 bispecific antibody | 51.6% response rate |
| Hopkins perioperative trial | 28.6 months median survival |
| Baylor-Duke trial opens | Chemo + immunotherapy before surgery |
| CONFIRM biomarker analysis | Predicting immunotherapy response |
2025 was a landmark year for mesothelioma treatment research, with multiple promising drugs advancing through clinical trials and new combination approaches showing unprecedented results. Here’s a comprehensive review of the year’s most important developments.
New Drug Classes: TEAD Inhibitors
The Breakthrough: VT3989
The biggest news in mesothelioma drug development was VT3989 from Vivace Therapeutics:
| Metric | VT3989 Results | Historical Comparison |
|---|---|---|
| Overall response rate | 32% | ~10-15% (second-line) |
| Disease control rate | 86% | ~40-50% |
| Median PFS | 40 weeks | 15 weeks |
| FDA designation | Fast Track | : |
VT3989 targets TEAD proteins, blocking a growth pathway commonly disrupted in mesothelioma. The drug is now advancing to Phase 3 trials.
The Setback: Novartis IAG933
Novartis discontinued development of its competing TEAD inhibitor IAG933, leaving VT3989 as the class leader. This highlights both the challenges of drug development and the significance of VT3989’s success.
What this means for patients: A potentially new treatment class for relapsed mesothelioma, with Phase 3 trials beginning in 2026.
Bispecific Antibodies: BNT327
BioNTech’s Promising Data
At ASCO 2025, BioNTech presented compelling data on BNT327:
| Endpoint | BNT327 Results |
|---|---|
| Overall response rate | 51.6% |
| Disease control rate | 90.3% |
| Peritoneal response | 83.3% (subgroup) |
BNT327 is a bispecific antibody targeting both PD-L1 and VEGF, attacking both immune suppression and tumor blood supply simultaneously.
What this means for patients: A potentially powerful new immunotherapy option, especially for peritoneal mesothelioma.
Perioperative Immunotherapy: The New Frontier
Hopkins Trial: Before and After Surgery
The Johns Hopkins perioperative trial demonstrated that combining immunotherapy with surgery produces exceptional results:
| Outcome | Trial Results | Historical Average |
|---|---|---|
| Median overall survival | 28.6 months | ~18 months |
| Surgical completion rate | 80%+ | ~70% |
| Recurrence-free at 1 year | 36% | : |
This approach gives immunotherapy before surgery (to shrink tumors and prime the immune system) and continues after surgery (to eliminate remaining disease).
Baylor-Duke Trial Opens
The Baylor-Duke chemoimmunotherapy trial is now recruiting, testing chemotherapy plus dual immunotherapy before surgery:
| Trial Element | Detail |
|---|---|
| Treatment | Durvalumab + tremelimumab + chemo |
| Setting | Before surgery |
| Population | Operable mesothelioma |
| Status | Actively recruiting |
What this means for patients: Surgical candidates now have trial options for perioperative immunotherapy.
Understanding Treatment Response: Biomarkers
CONFIRM Trial Analysis
The CONFIRM trial biomarker analysis provided crucial insights into predicting immunotherapy response:
| Finding | Implication |
|---|---|
| PD-L1 status doesn’t predict response | Don’t exclude patients based on PD-L1 |
| Inflammation signatures matter | May help select patients |
| Both subtypes benefit | Epithelioid and non-epithelioid |
This research moves us toward precision medicine in mesothelioma, matching patients to treatments they’re most likely to benefit from.
With multiple promising treatments in development, ask your oncologist about clinical trial eligibility. Specialized mesothelioma centers have access to trials testing VT3989, BNT327, perioperative immunotherapy combinations, and other emerging approaches.
Arginine Depletion Matures
ATOMIC-Meso Long-Term Data
Pegargiminase (ADI-PEG20) continued to show benefit in the difficult-to-treat non-epithelioid population:
| Outcome | With Pegargiminase | Without |
|---|---|---|
| Median OS | 9.3 months | 7.7 months |
| 3-year survival | 4x higher | Baseline |
What this means for patients: A potential option specifically for sarcomatoid and biphasic mesothelioma, which responds poorly to other treatments.
FDA and Regulatory Developments
2025 Regulatory Milestones
| Development | Significance |
|---|---|
| VT3989 Fast Track | Expedited review pathway |
| EPA asbestos ban implementation | Reducing future exposures |
| FDA talc testing rule withdrawn | Regulatory uncertainty |
Treatment Landscape Summary: 2025
Current Standard of Care
| Setting | Treatment | Evidence Level |
|---|---|---|
| First-line | Opdivo + Yervoy OR Chemo | FDA approved |
| First-line (perioperative) | Immunotherapy + surgery | Emerging |
| Second-line | Nivolumab or clinical trial | CONFIRM data |
Emerging Options
| Drug/Approach | Stage | Expected Timeline |
|---|---|---|
| VT3989 | Phase 3 starting | 2026-2029 |
| BNT327 | Mid-stage | 2027+ |
| Perioperative combinations | Active trials | Ongoing |
What to Watch in 2026
Anticipated Developments
| Development | Expected |
|---|---|
| VT3989 Phase 3 initiation | Early 2026 |
| More perioperative trial results | Mid-2026 |
| BNT327 expanded data | ASCO 2026 |
| New combination trials | Throughout year |
What This Means for Patients Now
Action Steps
- Discuss clinical trials: Ask your oncologist about new options
- Consider comprehensive testing: Biomarkers may guide treatment
- Seek expert care: Specialized centers have trial access
- Stay informed: Treatment landscape is evolving rapidly
Questions to Ask Your Doctor
- Am I eligible for any clinical trials?
- Should I have comprehensive biomarker testing?
- Would perioperative immunotherapy be appropriate for my case?
- What’s the best sequence of treatments for my situation?
The Big Picture
2025 demonstrated that mesothelioma treatment is advancing on multiple fronts:
| Area | Progress |
|---|---|
| New drug targets | TEAD inhibitors validating the approach |
| New mechanisms | Bispecific antibodies showing promise |
| Treatment combinations | Perioperative immunotherapy working |
| Patient selection | Biomarkers improving |
The field is moving from “one size fits all” toward precision medicine, matching patients to treatments based on their tumor’s specific characteristics.
Related Articles
- VT3989 TEAD Inhibitor Breakthrough
- BioNTech BNT327 ASCO Data
- Hopkins Perioperative Trial
- ATOMIC-Meso Results
- CONFIRM Biomarker Analysis
- Mesothelioma Clinical Trials Guide
What was the biggest treatment advance in 2025?▼
VT3989, a TEAD inhibitor from Vivace Therapeutics, showed unprecedented results: 32% response rate, 86% disease control, and 40-week median progression-free survival in relapsed patients. It received FDA Fast Track designation and is advancing to Phase 3 trials.
What are the current treatment options?▼
First-line: Opdivo + Yervoy (immunotherapy) OR chemotherapy (both FDA-approved). Second-line: nivolumab or clinical trial. Perioperative immunotherapy (before and after surgery) is emerging as a promising approach with 28.6 months median survival in the Hopkins trial.
Who should consider clinical trials?▼
Ask your oncologist if you’re eligible for trials testing: VT3989 (TEAD inhibitor), BNT327 (bispecific antibody), perioperative immunotherapy combinations (Baylor-Duke trial actively recruiting), or arginine depletion (for non-epithelioid disease). Specialized centers have the broadest trial access.
What biomarker testing should I request?▼
The CONFIRM analysis showed PD-L1 status doesn’t reliably predict immunotherapy response in mesothelioma—patients benefited regardless. However, comprehensive biomarker testing may identify other factors guiding treatment selection. Ask your oncologist about available testing.