Phase 3 is the final — and biggest — hurdle for a clinical trial. Few studies reach this point, and even fewer succeed.
The Checkmate-743 trial for mesothelioma is an exception.
The study tested an immunotherapy pairing of nivolumab and ipilimumab. Their brand names are Opdivo and Yervoy, respectively. They far outperformed standard chemotherapy in extending the survival of people with pleural mesothelioma.
The details of the trial, which took place in Europe, are below:
- 605 patients randomly assigned to one of two groups
- 303 people received nivolumab (3 mg/kg every two weeks) plus ipilimumab (1 mg/kg every six weeks)
- 302 participants received chemotherapy (pemetrexed and either cisplatin or carboplatin)
The group that received immunotherapy survived, on average, months longer than the chemotherapy batch. The two-year survival rates were:
- 40.8% for the immunotherapy patients
- 27% for the chemotherapy arm
The median overall survival was:
- 18.1 months for immunotherapy
- 14.1 months for chemotherapy
The median overall survival by cell type was:
- 18.7 months (epithelioid) and 18.1 months (non-epithelioid) for patients receiving immunotherapy
- 16.5 months (epithelioid) and 8.8 months (non-epithelioid) for the chemotherapy group
Paul Baas, who worked at the Netherlands Cancer Institute and helped lead the study, said in a press release that this is “evidence that a dual immunotherapy combination showed superior, sustained overall survival benefit compared to chemotherapy.”
“The CheckMate-743 data support the potential for nivolumab plus ipilimumab to become a new standard of care,” Dr. Baas added.
If you’d like more information on this clinical trial, treatment options, other studies or finding a cancer center, we can help. Please email our patient advocate and registered nurse, Jenna Campagna, at firstname.lastname@example.org.
What These Results Mean for People With Mesothelioma
The study leaders presented the results Aug. 8 at the 2020 World Conference on Lung Cancer Virtual Presidential Symposium. Since this study was in phase 3, the success could lead to a new approval from the U.S. Food and Drug Administration (FDA). Phase 3 is often the last step before the FDA must review a drug or protocol and either approve or deny it.
The FDA has already approved a pair of emerging treatment methods for pleural mesothelioma after a 15-year stretch of no approvals. One year ago, the FDA approved a tumor treating fields device (NovoTTF-100L System) for pleural mesothelioma cases that can’t be treated with surgery.
A few months ago, the FDA approved Keytruda (the brand name for the immunotherapy drug pembrolizumab) for pleural mesothelioma with high levels of PD-L1 protein expression.
Prior to these two approvals, the chemotherapy combination of cisplatin and pemetrexed was the only FDA-approved treatment for mesothelioma. Since Checkmate-743 tested immunotherapy against these chemotherapy drugs, the improved survival merits FDA approval.
The other factor that could derail a clinical trial is safety. If a treatment improves survival but has notable safety concerns, then the FDA won’t approve it.
Fortunately, the Checkmate-743 combination of nivolumab and ipilimumab didn’t show any new safety worries during the Phase 3 study. An American study is testing nivolumab and ipilimumab before and after mesothelioma surgery, so the combination is on the minds of many specialists around the globe.
What Nivolumab and Ipilimumab Do to Mesothelioma Tumors
Nivolumab and ipilimumab are checkpoint inhibitors, which means they stop cancerous proteins from achieving their main goal. Mesothelioma tumors sometimes express high levels of specific proteins, which serve as protectors for the disease.
T-cells, a type of white blood cell, respond to foreign substances in your body. They determine the immune reaction to unknown or unwanted intruders. Cancer, for instance, merits an immune response from T-cells.
These cells have protein receptors called PD-1 and CTLA-4. Mesothelioma cells sometimes have the proteins PD-L1 and B7. These proteins can communicate with T-cell receptors (PD-L1 with PD-1 and B7 with CTLA-4) and trick your body’s T-cells into ignoring mesothelioma cells.
Nivolumab blocks the communication between PD-1 and PD-L1. This wall keeps T-cells more aware and able to fight mesothelioma.
Ipilimumab blocks the contact between CTLA-4 and B7. This encourages T-cells to attack mesothelioma cells.
Show Sources & Author
- Nivolumab Plus Ipilimumab Improves OS in Malignant Pleural Mesothelioma. Cancer Network. Retrieved from: https://www.cancernetwork.com/view/nivolumab-plus-ipilimumab-improves-os-in-malignant-pleural-mesothelioma. Accessed: 08/11/2020.
- Checkmate 743 shows that dual immunotherapy, nivolumab + ipilimumab improves overall survival for patients with previously untreated mesothelioma. International Association for the Study of Lung Cancer. Retrieved from: https://www.eurekalert.org/pub_releases/2020-08/iaft-c7s080520.php. Accessed: 08/11/2020.
- Study of Nivolumab Combined With Ipilimumab Versus Pemetrexed and Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma Patients (CheckMate743). Clinicaltrials.gov. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT02899299. Accessed: 08/11/2020.
- CTLA-4. National Cancer Institute. Retrieved from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ctla-4. Accessed: 08/11/2020.