FDA-Approved Immunotherapies for Mesothelioma
As of 2026, three immune checkpoint inhibitors have received FDA approval as first-line treatments for mesothelioma:
| Drug | Brand Name | Approval | Target |
|---|---|---|---|
| Nivolumab | Opdivo | October 2020 | PD-1 |
| Ipilimumab | Yervoy | October 2020 | CTLA-4 |
| Pembrolizumab | Keytruda | 2023 (combo) | PD-1 |
These checkpoint inhibitors work by “releasing the brakes” on your immune system, allowing T cells to recognize and attack cancer cells.
CheckMate 743: The Landmark Trial
The combination of nivolumab plus ipilimumab was approved based on the CheckMate 743 trial results:
| Measure | Nivolumab + Ipilimumab | Chemotherapy |
|---|---|---|
| Median overall survival | 18.1 months | 14.1 months |
| 2-year survival | 41% | 27% |
| 3-year survival | 23% | 15% |
This represents a 4-month improvement in median survival and a 14% absolute improvement in 2-year survival compared to standard chemotherapy.
How Immunotherapy Works
Checkpoint Inhibitors
Cancer cells can hide from the immune system by activating “checkpoints” that tell T cells to stand down. Immunotherapy drugs block these checkpoints:
PD-1 Inhibitors (Nivolumab, Pembrolizumab)
- Block the PD-1 protein on T cells
- Prevent cancer cells from activating the “off switch”
- Allow T cells to attack cancer
CTLA-4 Inhibitors (Ipilimumab)
- Block CTLA-4, another immune checkpoint
- Boost overall immune activation
- Work synergistically with PD-1 inhibitors
Combining PD-1 and CTLA-4 inhibitors produces better results than either alone because they target different checkpoints. The dual approach creates a more comprehensive immune response.
Ongoing Clinical Trials (2025-2026)
DREAM3R Trial
A Phase III study comparing treatment approaches:
- Arm 1: Durvalumab + chemotherapy
- Arm 2: Chemotherapy alone
- Arm 3: Nivolumab + ipilimumab
Preliminary result: The durvalumab + chemotherapy arm showed 20.4 months median overall survival.
TEADES Trial (December 2025)
Orion Pharma initiated this Phase 2 trial evaluating ODM-212, an oral pan-TEAD inhibitor:
- Targets Hippo pathway dysfunction
- Enrolling approximately 300 patients globally
- Represents a shift toward targeted mechanisms beyond traditional checkpoint inhibition
- Endpoints: Response rate, progression-free survival, overall survival
Alliance A092001 Trial
Sponsored by the National Cancer Institute:
- Evaluates atezolizumab (Tecentriq) + bevacizumab (Avastin) + chemotherapy
- Compares against chemotherapy + Avastin alone
- Targets anti-angiogenesis combined with immunotherapy
SMARTEST Trial
A multimodal approach combining:
- Radiation therapy
- Cyclophosphamide
- Surgery
- Tremelimumab + Durvalumab
IMPRINT Trial
Phase I study evaluating:
- Pembrolizumab combined with intensity-modulated pleural radiation therapy
- Investigates radiation as immune system booster
Emerging Immunotherapy Approaches
CAR-T Cell Therapy
Clinical trials are testing CAR-T therapies that target mesothelin, a protein highly expressed in mesothelioma:
- Mesothelin-targeting autologous CAR T products
- Tumor-infiltrating lymphocyte (TIL) therapy combined with chemotherapy
- Genetic modification of patient’s own immune cells
Cancer Vaccines
Therapeutic vaccines under investigation:
- Dendritic cell vaccines
- Tumor antigen vaccines
- Personalized neoantigen vaccines
Biomarker-Driven Treatment
2025 research demonstrated that circulating tumor DNA (ctDNA) levels in blood samples can predict treatment response:
- Declining ctDNA correlates with positive treatment outcomes
- May enable more personalized treatment decisions
- Allows earlier identification of non-responders
ADI-PEG20: Breakthrough Results
The Phase III ATOMIC-Meso trial (2024 data) showed remarkable results for ADI-PEG20 (pegarginimase) when added to chemotherapy:
| Measure | ADI-PEG20 + Chemo | Chemotherapy Alone |
|---|---|---|
| 3-year survival | 4x higher | Baseline |
| Median OS improvement | +2 months | : |
| Progression-free survival | 6 months | : |
This arginine-depleting therapy exploits mesothelioma cells’ inability to produce their own arginine.
Who Responds Best to Immunotherapy?
Favorable Factors
- Non-epithelioid cell types: Paradoxically, sarcomatoid mesothelioma responds better to immunotherapy
- Higher PD-L1 expression: More targets for the drugs
- Good performance status: Better able to tolerate treatment
- Lower tumor burden: Improves immune system effectiveness
Less Favorable Factors
- Very low PD-L1 expression
- Poor overall health
- Heavily pre-treated disease
- Significant immunosuppression
Side Effects
Immunotherapy side effects differ from chemotherapy:
Common:
- Fatigue (30-40%)
- Skin rash (20-30%)
- Diarrhea (15-25%)
- Nausea (15-20%)
While less common, immune-related side effects require prompt attention: thyroid dysfunction, pneumonitis (lung inflammation), hepatitis (liver inflammation), and colitis (intestinal inflammation). Report new symptoms immediately.
Management:
- Most side effects are manageable with steroids
- Early reporting is crucial
- Dose adjustments or treatment pauses may be needed
Immunotherapy vs. Chemotherapy
| Factor | Immunotherapy | Chemotherapy |
|---|---|---|
| Median survival | 18+ months | 12-14 months |
| 3-year survival | 23% | 15% |
| Side effect profile | Immune-related | Blood counts, nausea |
| Long-term survivors | More common | Less common |
| Works for all patients | No | Generally yes |
Immunotherapy may produce durable responses in some patients, meaning the cancer stays controlled for years. This is less common with chemotherapy.
Combination Approaches
The most promising results come from combining immunotherapy with other treatments:
Immunotherapy + Chemotherapy
- Durvalumab + chemo: 20.4 months median survival
- Pembrolizumab + chemo: 17 months median survival
Multimodal Therapy
For eligible patients:
- Surgery: Remove visible tumor
- Chemotherapy: Kill microscopic disease
- Immunotherapy: Sustained immune response
- Radiation: Target remaining cells
This approach produces the best outcomes for surgical candidates.
Finding Clinical Trials
Resources for locating immunotherapy trials:
- ClinicalTrials.gov: Search “mesothelioma immunotherapy”
- NCI Cancer Centers: Many lead trials
- Mesothelioma specialty centers: Often have access to trials
- Your oncologist: Can identify trials you may qualify for
Am I a candidate for immunotherapy?▼
Candidates typically have unresectable mesothelioma, adequate performance status, and no contraindications. Sarcomatoid cell types may particularly benefit compared to chemotherapy alone.
What is my PD-L1 expression level?▼
PD-L1 expression can help predict response to immunotherapy. Higher levels suggest more targets for checkpoint inhibitors, though responses occur at all expression levels.
Should I receive immunotherapy alone or with chemotherapy?▼
This depends on your cell type, overall health, and treatment goals. Combination approaches (durvalumab + chemo: 20.4 months) show promising results in recent trials.
What clinical trials am I eligible for?▼
Resources include ClinicalTrials.gov, NCI Cancer Centers, and mesothelioma specialty centers. Your oncologist can identify trials matching your specific situation.
What side effects should I watch for?▼
Common effects include fatigue, skin rash, and diarrhea. Report any new shortness of breath, severe diarrhea, jaundice, or significant fatigue—these may indicate immune-related inflammation.