Opdivo (nivolumab) is an immunotherapy medicine developed and marketed by Bristol-Myers Squibb. Opdivo may be beneficial for patients with a number of cancers on its own, or in combination with other therapies.
The cancers that Opdivo is approved to treat include certain cases of advanced non-small-cell lung cancer (NSCLC), advanced melanoma, some cases of advanced renal cell carcinoma (RCC, kidney cancer), and certain types of metastatic colorectal cancers.
Opdivo may also be used in previously treated patients with the following cancers: advanced small-cell lung cancer (SCLC), certain types of esophageal cancer, advanced urothelial carcinoma, classical Hodgkin lymphoma, and hepatocellular carcinoma (HCC).
How does Opdivo work?
Opdivo is an antibody that works with the immune system to treat cancer.
T-cells are white blood cells that are important for the immune response. They normally are able to recognize cancer cells as abnormal and kill them. Checkpoints exist to prevent T-cells from attacking healthy cells. One of these checkpoints is the PD-1 pathway.
T-cells normally produce receptor proteins called PD-1. When proteins called PD-L1 and PD-L2 bind to PD-1, they block the action of T-cells. Some tumor cells produce PD-L1 and PD-L2 to evade T-cells. By producing these proteins, in other words, the cancer cells “mask” themselves from the immune system.
Opdivo works by binding to the PD-1 receptor, and blocking its ability to interact with PD-L1 and PD-L2. This allows T-cells again to be able to find and destroy cancer cells.
Because it acts by removing an immune system checkpoint, Opdivo also may cause T-cells to attack healthy cells.
Opdivo in clinical trials
Bristol-Myers Squibb has been running a broad, global development program to study Opdivo as a monotherapy or in combination with other treatments in more than 35 clinical trials worldwide. Those trials include more than 7,000 patients with multiple tumor types.
The U.S. Food and Drug Administration (FDA) approved a combination of Opdivo with low-dose Yervoy (ipilimumab) for the initial treatment of people with metastatic NSCLC. This approval was based on the results of the Phase 3 CheckMate-227 clinical trial (NCT02477826). During this trial, the combination immunotherapy significantly increased patient survival and duration of response compared to chemotherapy.
CheckMate-017 and CheckMate-057 (NCT01642004 and NCT01673867, respectively) were two pivotal Phase 3 clinical trials that evaluated Opdivo versus Taxotere (docetaxel) in patients with squamous NSCLC and non-squamous NSCLC. Data from these two trials reinforced the survival benefit demonstrated with Opdivo for this group of patients even after three years. The results represent the longest follow-up data reported to date for a PD-1 inhibitor versus chemotherapy in NSCLC.
Opdivo’s approval to treat melanoma was based on data from a Phase 3 clinical trial (NCT01721746) called CheckMate-037. This trial studied 405 patients with advanced melanoma. It compared the effect of Opdivo with that of other chemotherapy agents, such as DTIC-Dome (dacarbazine), or intravenous carboplatin plus Taxol (paclitaxel). The results showed that Opdivo demonstrated a better response rate than chemotherapy agents. It also caused fewer serious adverse effects.
CheckMate-238 (NCT02388906) is an ongoing Phase 3 study of Opdivo versus Yervoy in patients who have undergone complete resection of stage 3b/c or stage 4 melanoma, and demonstrated a significant improvement in recurrence-free survival compared to Yervoy.
A Phase 3 clinical trial (NCT02231749) called CheckMate -214 compared the combination of Opdivo and Yervoy versus Sutent (sunitinib) in patients with advanced or high-risk RCC. Although the trial is still ongoing, the combination already demonstrated a significant increase in overall survival in this patient population. This was the basis for FDA approval.
Metastatic colorectal cancer
A Phase 2 clinical trial (NCT02060188) called CheckMate-142 is evaluating the combination of Opdivo and low-dose Yervoy in patients with colorectal carcinoma that has previously been treated with fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy. Although this trial is still ongoing, the FDA has approved this treatment combination based on intermediate data.
The FDA approval of Opdivo to treat esophageal cancer was based on data from a Phase 3 clinical trial (NCT02569242) called ATTRACTION-3. The study included 419 patients who randomly received either Opdivo or the standard chemotherapies Taxotere or Taxol. All treatments were given into the bloodstream until disease progression or unacceptable toxicity. Trial results demonstrated that Opdivo significantly extends survival time compared with the standard chemotherapies.
A Phase 1/2 clinical trial (NCT01592370) called CheckMate-039 is evaluating patients with either Hodgkin’s lymphoma, non-Hodgkin lymphoma, or myeloma. The trial is still ongoing, but the results from the group with Hodgkin lymphoma have shown high levels of response in patients with relapsed or refractory disease. Intermediate results put the overall response rate at 87%, with 13% of patients showing stable disease.
A Phase 1/2 clinical trial (NCT01658878) called Checkmate-040 is testing the safety and efficacy of Opdivo in treating HCC patients who have previously been treated with sorafenib. The promising intermediate results have resulted in an accelerated FDA approval for this combination in treating HCC, dependent on validation in future clinical trials.
Other information about Opdivo
The most common side effects associated with the use of Opdivo are fatigue, shortness of breath, muscle pain, decreased appetite, cough, nausea, and constipation. Serious side effects may include inflammation of the lungs, colon (which may lead to tears or holes in the colon), liver, kidneys (which may lead to kidney failure), and brain. Opdivo may lead to problems in hormone glands, skin, and other organs, as well as severe infusion-related reactions.
Last updated: June 22, 2020
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