A phase 2 clinical trial is studying whether adding the immunotherapy drug Keytruda to chemotherapy before surgery can improve outcomes for certain patients with pleural mesothelioma. The CHIMERA trial is evaluating Keytruda, also known as pembrolizumab, with platinum-based chemotherapy and pemetrexed before mesothelioma surgery. Participants who undergo surgery then receive additional Keytruda without chemotherapy.
Researchers hope this approach can eliminate more cancer cells before surgery and reduce the risk of mesothelioma returning afterward. However, the trial has not reported results, and this treatment approach is not currently a standard treatment for resectable mesothelioma.
CHIMERA is a phase 2, open-label clinical trial conducted at multiple medical centers in Italy. The study began enrolling patients in November 2024 and was designed to include approximately 40 adults with stage 1 through stage 3A pleural mesothelioma.
As of July 2026, investigators reported that enrollment had been completed. Results are not yet available.
Participants must have epithelioid or biphasic pleural mesothelioma and cannot have received previous systemic treatment for the disease. A multidisciplinary medical team must also determine that the patient is healthy enough for surgery and that the tumor may be surgically removed.
The study does not include patients with sarcomatoid mesothelioma or mesothelioma that began in the abdomen, heart lining, or testicular lining.
Because CHIMERA is a single-arm trial, all participants receive the investigational treatment. There is no separate group receiving chemotherapy alone for comparison.
Treatment in the CHIMERA trial occurs in three stages:
Researchers are also collecting blood samples, tumor tissue, and medical images to evaluate treatment response and look for characteristics that may help predict which patients benefit.
Treatment administered before surgery is called neoadjuvant therapy. It may help shrink or weaken a tumor and attack cancer cells that cannot be seen through medical imaging.
Keytruda is an immune checkpoint inhibitor. It blocks a protein called PD-1, which cancer cells may use to avoid detection by the immune system. Blocking PD-1 can help immune cells recognize and attack cancer.
In the United States, Keytruda combined with pemetrexed and platinum chemotherapy is approved for adults with unresectable advanced or metastatic pleural mesothelioma. Unresectable means the cancer cannot be completely removed through surgery.
The CHIMERA trial is exploring a different use of the combination. Researchers want to know whether it may also benefit carefully selected patients with earlier-stage, resectable pleural mesothelioma when administered before surgery and followed by additional immunotherapy.
This perioperative approach has not been approved as a standard treatment for resectable mesothelioma.
The trial’s primary goal is to measure the pathological complete response rate. A pathological complete response means doctors find no living cancer cells in the primary tumor or sampled lymph nodes removed during surgery.
In an earlier multicenter phase 2 trial, approximately 5% of patients achieved a pathological complete response after receiving chemotherapy before mesothelioma surgery. CHIMERA was designed to determine whether adding Keytruda could increase that rate to approximately 18%.
Researchers will also evaluate:
These measurements may help researchers decide whether the treatment deserves further study in a larger clinical trial.
Immunotherapy has changed how doctors treat many patients with unresectable pleural mesothelioma. Researchers are now investigating whether it can also improve multimodal treatment for carefully selected surgical patients.
Multimodal treatment combines therapies such as chemotherapy, surgery, and immunotherapy. The goal is to attack mesothelioma in several ways instead of relying on a single treatment.
Complete responses to chemotherapy before mesothelioma surgery have remained uncommon. If adding Keytruda eliminates more viable tumor cells before surgery, the approach could warrant additional research.
The study may also help identify biomarkers associated with better responses to pembrolizumab. This information could support more personalized treatment decisions in the future.
CHIMERA is a small, single-arm study involving a highly selected group of surgical patients. It has not yet produced evidence that the treatment helps patients live longer or prevents mesothelioma from returning.
Because there is no randomized comparison group, researchers will compare the results with outcomes reported in earlier studies. This makes it more difficult to determine whether any improvement is directly attributable to Keytruda.
The role of surgery in mesothelioma treatment also remains an area of debate. The MARS 2 trial did not find a survival advantage from adding extended pleurectomy and decortication to chemotherapy and reported more serious complications among patients assigned to surgery.
Surgery may still be considered for select patients based on cancer stage, cell type, overall health, and the experience of the treatment center. However, it is not appropriate for everyone with pleural mesothelioma.
Patients should not interpret the CHIMERA trial as evidence that surgery combined with Keytruda is superior to other available treatments. Larger randomized studies may be necessary before this approach could become a new standard of care.
Clinical trials can provide access to emerging treatments, but every study has specific eligibility requirements. CHIMERA is being conducted in Italy and has reportedly completed enrollment, so it is not currently a practical option for patients seeking a clinical trial.
Other studies may be investigating immunotherapy, surgery and new drug combinations for mesothelioma. A mesothelioma specialist can review a patient’s diagnosis, cancer stage, cell type, treatment history and overall health to identify potentially appropriate trials.
Patients considering clinical research may want to ask:
Mesothelioma Hub can help patients and families connect with experienced mesothelioma doctors and treatment centers. A specialist can explain available therapies and help determine whether another clinical trial may be appropriate. You can also download our free mesothelioma guide for more information about treatment, support resources, and next steps. If you or a loved one was diagnosed with mesothelioma after asbestos exposure, request a free case evaluation to learn whether you may qualify for financial compensation.
Madeline works for the patient advocate team and writes about asbestos exposure and mesothelioma. She is passionate about helping families in the mesothelioma community.
ClinicalTrials.gov. (2026, January 13). Induction chemo+immunotherapy in resectable epithelioid and biphasic pleural mesothelioma (CHIMERA study) (NCT06155279). https://clinicaltrials.gov/study/NCT06155279
Passello, G., Scattolin, D., Faccioli, E., et al. (2026). CHIMERA: A phase II study of neoadjuvant pembrolizumab in combination with cisplatin or carboplatin and pemetrexed followed by surgery and adjuvant pembrolizumab in resectable pleural mesothelioma. Clinical Lung Cancer, 27, 31–35. https://doi.org/10.1016/j.cllc.2026.05.004
Targeted Oncology Staff. (2026, July 27). Phase 2 CHIMERA trial tests neoadjuvant pembrolizumab in mesothelioma. Targeted Oncology. https://www.targetedonc.com/view/phase-2-chimera-trial-tests-neoadjuvant-pembrolizumab-in-mesothelioma
Tostes, F. T., Zugman, M., Paes, V. R., & Schvartsman, G. (2022). Complete pathological response after neoadjuvant chemo-immunotherapy in malignant pleural mesothelioma. Frontiers in Oncology, 12, 836751. https://doi.org/10.3389/fonc.2022.836751