Opdivo (nivolumab) - 12 indications

Scroll down for information on each indication:

• for the treatment of unresectable or metastatic melanoma; approved December 2014
• for the treatment of metastatic squamous non-small cell lung cancer; approved March 2015
• for the treatment of advanced renal cell carcinoma; approved November 2015
• for the treatment of classical Hodgkin lymphoma; approved May 2016
• for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck; approved November 2016
• for the treatment of metastatic urothelial carcinoma; approved February 2017
• for the treatment of hepatocellular carcinoma; approved September 2017; indication withdrawn in July of 2021
• for the treatment of MSI-H or dMMR metastatic colorectal cancer; approved August 2018
• for the treatment of advanced, recurrent or metastatic esophageal squamous cell carcinoma; approved June of 2020
• for use in combination with ipilimumab (Yervoy) for the first-line treatment of unresectable malignant pleural mesothelioma; approved October of 2020
• for the treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of PD-L1 expression status; approved April of 2021
• for the neoadjuvant treatment of certain adult patients with resectable non-small cell lung cancer; approved March of 2022

General Information

Opdivo (nivolumab) is a programmed death-1 (PD-1) immune checkpoint inhibitor. 

Opdivo is specifically indicated for the following:

• for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.
• for the treatment of non-small cell lung cancer:
  •  adult patients with metastatic non-small cell lung cancer expressing PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with ipilimumab
  • adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations as first-line treatment, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy.
  • patients with metastatic non-small cell lung cancer and progression on or after platinum-based chemotherapy
• for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
• for the treatment of patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin.
• for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy.
• adjuvant treatment of patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC
• for patients with locally advanced or metastatic urothelial carcinoma who: • have disease progression during or following platinum-containing chemotherapy • have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib, for use as a single agent or in combination with ipilimumab. Monotherapy indication withdrawn in July of 2021
• for adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, as a single agent or in combination with ipilimumab.
• for unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapy until disease progression or unacceptable toxicity. 
• for use in combination with ipilimumab (Yervoy) for the first-line treatment of unresectable malignant pleural mesothelioma
• for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of PD-L1 expression status in combination with fluoropyrimidine- and platinum-containing chemotherapy until disease progression, unacceptable toxicity or for up to two years.
• for use in combination with platinum-doublet chemotherapy every three weeks for three cycles for adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer in the neoadjuvant setting

Opdivo is supplied as an injection for intravenous administration. Scroll down for specific dosing/administration instructions for each indication.

Mechanism of Action

Opdivo (nivolumab) is a programmed death receptor-1 (PD-1) blocking antibody. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits Tcell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 Reference ID: 4622792 59 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

Side Effects

Adverse effects associated with the use of Opdivo monotherapy may include, but are not limited to, the following:

• fatigue
• rash
• musculoskeletal pain
• pruritus
• diarrhea
• nausea
• asthenia
• cough
• dyspnea
• constipation
• decreased appetite
• back pain
• arthralgia
• upper respiratory tract infection
• pyrexia
• headache
• abdominal pain
• vomiting

Adverse effects associated with the use of Opdivo in combination with fluoropyrimidine- and platinum-containing chemotherapy may include, but are not limited to, the following:

• peripheral neuropathy
• nausea
• fatigue
• diarrhea
• vomiting
• decreased appetite
• abdominal pain
• constipation
• musculoskeletal pain

Adverse effects associated with the use of Opdivo in combination with ipilimumab may include, but are not limited to, the following:

• fatigue
• diarrhea
• rash
• pruritus
• nausea
• musculoskeletal pain
• pyrexia
• cough
• decreased appetite
• vomiting
• abdominal pain
• dyspnea
• upper respiratory tract infection
• arthralgia
• headache
• hypothyroidism
• decreased weight
• dizziness

Adverse effects associated with the use of Opdivo in combination with ipilimumab and platinum-doublet chemotherapy may include, but are not limited to, the following:

• fatigue
• musculoskeletal pain
• nausea
• diarrhea
• rash
• decreased appetite
• constipation
• pruritus

Indication 1 - unresectable or metastatic melanoma

approved December 2014

Dosing/Administration

Opdivo is supplied as a solution for intravenous administration. The recommended dose of Opdivo is 3 mg/kg administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.

Clinical Trial Results

The FDA approval of Opdivo for melanoma was based on a multicenter, open-label trial that randomized patients with unresectable or metastatic melanoma to receive either Opdivo administered intravenously at 3 mg/kg every 2 weeks or investigator’s choice of chemotherapy, either single-agent dacarbazine 1000 mg/m2 every 3 weeks or the combination of carboplatin AUC 6 every 3 weeks plus paclitaxel 175 mg/m2 every 3 weeks. Patients were required to have progression of disease on or following ipilimumab treatment and, if BRAF V600 mutation positive, a BRAF inhibitor. Tumor assessments were conducted 9 weeks after randomization then every 6 weeks for the first year, and every 12 weeks thereafter. Efficacy was evaluated in a single-arm, non-comparative, planned interim analysis of the first 120 patients who received Opdivo and in whom the minimum duration of follow up was 6 months. The major efficacy outcome measures in this population were confirmed objective response rate (ORR) as measured by blinded independent central review using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and duration of response. The ORR was 32%, consisting of 4 complete responses and 34 partial responses in Opdivo-treated patients. Of 38 patients with responses, 33 (87%) had ongoing responses with durations ranging from 2.6+ to 10+ months, which included 13 patients with ongoing responses of 6 months or longer. Objective responses were observed in patients with and without BRAF V600 mutation positive melanoma.

Indication 2 - metastatic squamous non-small cell lung cancer

approved March 2015

Dosing/Administration

3 mg/kg every 2 weeks with ipilimumab 1 mg/kg every 6 weeks

360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks and 2 cycles of platinum-doublet chemotherapy

240 mg every 2 weeks or 480 mg every 4 weeks

Clinical Trial Results

The FDA approval of Opdivo for metastatic squamous non-small cell lung cancer was based on a randomized, open-label study enrolling 272 patients with metastatic squamous NSCLC who had experienced disease progression during or after one prior platinum doublet-based chemotherapy regimen. Patients received Opdivo administered intravenously at 3 mg/kg every 2 weeks or docetaxel administered intravenously at 75 mg/m2 every 3 weeks. This study included patients regardless of their PD-L1 status. The first tumor assessments were conducted 9 weeks after randomization and continued every 6 weeks thereafter. The major efficacy outcome measure was overall survival (OS). The trial demonstrated a statistically significant improvement in OS for patients randomized to Opdivo as compared with docetaxel at the prespecified interim analysis when 199 events were observed (86% of the planned number of events for final analysis). The median survival was 9.2 months versus 6.0 months for the Opdivo versus docetaxel arms, respectively.

Indication 3 - advanced renal cell carcinoma

approved November 2015

Dosing/Administration

Opdivo is supplied as a solution for intravenous infusion. The recommended dose of Opdivo is 3 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

Clinical Trial Results

The FDA approval of Opdivo for renal cell carcinoma was based on an open-label, randomized study of 821 patients with advanced renal cell carcinoma whose disease worsened during or after treatment with an anti-angiogenic agent. Patients were treated with Opdivo or another type of kidney cancer treatment called everolimus (marketed as Afinitor). Those treated with Opdivo lived an average of 25 months after starting treatment compared to 19.6 months in those treated with Afinitor. This effect was observed regardless of the PD-L1 expression level of patients’ renal cell tumors. Additionally, 21.5 percent of those treated with Opdivo experienced a complete or partial shrinkage of their tumors, which lasted an average of 23 months, compared to 3.9 percent of those taking Afinitor, lasting an average of 13.7 months.

Indication 4 - classical Hodgkin lymphoma

approved May 2016

Dosing/Administration

Opdivo is supplied as a solution for intravenous administration. The recommended dose is 3 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

Clinical Trial Results

The FDA approval of Opdivo for classic Hodgkin's lymphoma was based on two single-arm, multicenter trials of nivolumab in adults with relapsed or refractory cHL. The trials enrolled patients regardless of PD-L1 expression status on Reed-Sternberg cells. The primary efficacy endpoint was objective response rate (ORR) as determined by an independent radiographic review committee.  Additional outcome measures included duration of response (DOR). Efficacy was evaluated in 95 patients previously treated with autologous HSCT and post-transplantation brentuximab vedotin.  Patients had a median of 5 prior systemic regimens and received a median of 17 doses of nivolumab. Single-agent nivolumab produced a 65% ORR, with 58% partial remission and 7% complete remission.  The median time-to-response was 2.1 months.  The estimated median DOR was 8.7 months.

Indication 5 - recurrent or metastatic squamous cell carcinoma of the head and neck

approved November 2016

Dosing/Administration

240 mg every 2 weeks (30-minute intravenous infusion) or 480 mg every 4 weeks (30-minute intravenous infusion) Until disease progression or unacceptable toxicity.

Clinical Trial Results

The FDA approval was based on the CheckMate -141 trial during which patients were randomly assigned to receive Opdivo, or therapy with methotrexate, docetaxel, or Erbitux (cetuximab; Merck). The researchers reported a 30% reduction in the risk of death and longer overall survival, but no significant differences in progression-free survival and objective response rate. 

Indication 6 - metastatic urothelial carcinoma

approved February 2017

Dosing/Administration

Opdivo is supplied as an injection for intravenous administration. The recommended dose for patients with locally advanced or metastatic urothelial carcinoma is either: • 240 mg every 2 weeks or • 480 mg every 4 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity. 

Clinical Trial Results

The FDA approval of Opdivo for urothelial cancer was based on CHECKMATE-275, which enrolled 270 patients with locally advanced or metastatic urothelial carcinoma who had disease progression during or following platinum containing chemotherapy or who had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen. Patients received 3 mg/kg of Opdivo by intravenous infusion every 2 weeks until unacceptable toxicity or either radiographic or clinical progression. Tumor response assessments were conducted every 8 weeks for the first 48 weeks and every 12 weeks thereafter. Major efficacy outcome measures included confirmed overall response rate (ORR) as assessed by independent radiographic review committee (IRRC) using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and duration of response (DOR). The confirmed ORR was 19.6%. Responses were observed in both PD-L1 expressors and non-expressors. The confirmed ORR in patients expressing PD-L1 ≥1% was 23.8%  and 16.1% in patients expressing PD-L1 <1%. In patients expressing PD-L1 ≥5%, the confirmed ORR was 28.4% and 15.8% in patients expressing PD-L1 <5%. The median duration of response was not reached in the overall population with a minimum follow-up of six months, and responses were ongoing in 77% of patients.

Indication 7 – hepatocellular carcinoma

approved September 2017

Dosing/Administration

240 mg every 2 weeks or 480 mg every 4 weeks.

1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks

Clinical Trial Results

The FDA approval of Opdivo for HCC was based on a 154-patient subgroup of CHECKMATE-040, a multicenter, open-label trial conducted in patients with hepatocellular carcinoma (HCC) who progressed on or were intolerant to sorafenib. Patients received 3 mg/kg of Opdivo by intravenous infusion every 2 weeks. Tumor assessments were conducted every 6 weeks for 48 weeks and every 12 weeks thereafter. The major efficacy outcome measure was confirmed overall response rate, as assessed by blinded independent central review using RECIST v1.1 and modified RECIST (mRECIST) for HCC. Duration of response was also assessed. Following Opdivo treatment, 22 (14.3%) of the 154 patients had a confirmed ORR; three patients had a complete response and 19 patients had a partial response. Of the 22 people who saw a response, 91% had a response that lasted 6 months or longer and 55% had a response that lasted 12 months or longer.

Indication 8 – MSI-H or dMMR metastatic colorectal cancer

approved August 2018

Dosing/Administration

Opdivo is supplied as an injection for intravenous administration. The recommended dose is as follows: 

• Single Agent: The recommended dose of Opdivo as a single agent is 240 mg every 2 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity.
• With Ipilimumab: The recommended dose of Opdivo is 3 mg/kg administered as an intravenous infusion over 30 minutes, followed by ipilimumab 1 mg/kg administered as an intravenous infusion over 30 minutes on the same day, every 3 weeks for 4 doses. After completing 4 doses of the combination, administer Opdivo 240 mg as a single agent every 2 weeks as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity. 

Clinical Trial Results

The FDA approval of Opdivo for colorectal cancer was based on CHECKMATE-142, a multicenter, non-randomized, multiple parallel-cohort, open-label study conducted in patients with locally determined dMMR or MSI-H metastatic CRC (mCRC) who had disease progression during or after prior treatment with fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy. Patients enrolled in the single agent Opdivo MSI-H mCRC cohort received Opdivo 3 mg/kg by intravenous infusion (IV) every 2 weeks. Patients enrolled in the Opdivo plus ipilimumab MSI-H mCRC cohort received Opdivo 3 mg/kg and ipilimumab 1 mg/kg IV every 3 weeks for 4 doses, followed by Opdivo 3 mg/kg IV as a single agent every 2 weeks. Treatment in both cohorts continued until unacceptable toxicity or radiographic progression. Tumor assessments were conducted every 6 weeks for the first 24 weeks and every 12 weeks thereafter. Efficacy outcome measures included overall response rate (ORR) and duration of response (DOR) as assessed by an independent radiographic review committee (IRRC) using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). A total of 74 patients were enrolled in the single-agent MSI-H mCRC Opdivo cohort. A total of 119 patients were enrolled in the Opdivo plus ipilimumab MSI-H mCRC cohort. In the CheckMate -142 trial, among patients (53/74) who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, 28% responded to treatment with Opdivo. The percentage of patients with a complete response was 1.9% (1/53) and the percentage of patients with a partial response was 26% (14/53). Among these responders, the median duration of response was not reached (range: 2.8+-22.1+ months). Among all enrolled patients, 32% responded to treatment with Opdivo; 2.7% (2/74) experienced a complete response, 30% (22/74) experienced a partial response.

Indication 9 - advanced, recurrent or metastatic esophageal squamous cell carcinoma

approved June of 2020

Dosing/Administration

Opdivo is supplied as a solution for intravenous administration. The recommended dose schedule is:

• 240 mg every 2 weeks or 480 mg every 4 weeks
• 240 mg every 2 weeks or 480 mg every 4 weeks in combination with chemotherapy regimen of fluoropyrimidine- and platinum-containing chemotherapy.
• 3 mg/kg every 2 weeks or 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks

Clinical Trial Results

The FDA accelerated approval was based on ATTRACTION-3, a Phase 3, multicenter, randomized, active-controlled, open-label global study evaluating Opdivo versus taxane chemotherapy (investigator’s choice of docetaxel or paclitaxel) in patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma, refractory or intolerant to at least one prior fluoropyrimidine- and platinum-based regimen. The trial included patients regardless of tumor PD-L1 status, but tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory. Patient enrollment occurred predominantly in Asia, with the United States and Europe accounting for the remainder. Patients were treated until disease progression, assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or unacceptable toxicity. Opdivo (n=210) demonstrated superior overall survival (OS) versus taxane chemotherapy (n=209) (investigator’s choice of docetaxel or paclitaxel). The median OS was 10.9 months for Opdivo compared to 8.4 months for docetaxel or paclitaxel.

The FDA approval of Opdivo (nivolumab) (injection for intravenous use) in combination with fluoropyrimidine- and platinum-containing chemotherapy and Opdivo plus Yervoy (ipilimumab) as a first-line treatment for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) regardless of PD-L1 status was based on the Phase 3 CheckMate -648 trial. In the trial, Opdivo in combination with chemotherapy demonstrated superior overall survival (OS) compared to chemotherapy alone, both in all randomized patients, a secondary endpoint and in patients whose tumors express PD-L. In all randomized patients the median OS (mOS) was 13.2 months with Opdivo in combination with chemotherapy versus 10.7 months with chemotherapy alone. In patients whose tumors express PD-L1 (≥1%) the mOS was 15.4 months for Opdivo in combination with chemotherapy versus 9.1 months with chemotherapy alone. The median progression-free survival (PFS) in all randomized patients was 5.8 months for Opdivo in combination with chemotherapy and 5.6 months for chemotherapy alone. 

Opdivo plus Yervoy also improved OS compared to chemotherapy in all-randomized patients, a secondary endpoint, and patients whose tumors express PD-L1 (≥1%), a primary endpoint. The mOS was 12.8 months with Opdivo plus Yervoy versus 10.7 months with chemotherapy alone in all randomized patients and 13.7 months with Opdivo plus Yervoy versus 9.1 months with chemotherapy alone in patients whose tumors express PD-L1 (≥1%). The median PFS in patients whose tumors express PD-L1 (≥1%), which was a co-primary endpoint, was 4.0 months for Opdivo plus Yervoy and 4.4 months for chemotherapy alone. Per pre-specified analysis, PFS did not meet statistical significance.

Indication 10 - unresectable malignant pleural mesothelioma

Approved October of 2020

Dosing/Administration

The recommended dose is 360 mg every 3 weeks (30-minute intravenous infusion) with ipilimumab 1 mg/kg every 6 weeks (30-minute intravenous infusion). When used in combination with ipilimumab treatment duration is until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.

Clinical Trial Results

The FDA approval of Opdivo/Yervoy for malignant pleural mesothelioma was based on CheckMate -743, an open-label, multi-center, randomized Phase 3 trial evaluating the combination compared to chemotherapy (pemetrexed and cisplatin or carboplatin) in patients with histologically confirmed unresectable malignant pleural mesothelioma and no prior systemic therapy or palliative radiotherapy within 14 days of initiation of therapy (n=605). Patients with interstitial lung disease, active autoimmune disease, medical conditions requiring systemic immunosuppression, or active brain metastasis were excluded from the trial. Treatment in both arms continued until disease progression or unacceptable toxicity or, in the Opdivo + Yervoy arm, up to 24 months. The primary endpoint of the trial was OS in all randomized patients. Patients treated with Opdivo + Yervoy (n=303) demonstrated superior overall survival (OS) versus the platinum-based standard of care chemotherapy (n=302), with a median OS (mOS) of 18.1 months versus 14.1 months, respectively. These results were observed after 22.1 months of minimum follow-up. At two years, 41% of patients treated with Opdivo + Yervoy were alive versus 27% of those treated with chemotherapy.

Indication 11 -  advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of PD-L1 expression status

approved April of 2021

Dosing/Administration

Opdivo is supplied as a solution for intravenous administration. The recommended dose is 240 mg every 2 weeks (30-minute intravenous infusion) with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks or 360 mg every 3 weeks (30-minute intravenous infusion) with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks.

Clinical Trial Results

The FDA approval of Opdivo for patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of PD-L1 expression status in combination with fluoropyrimidine- and platinum-containing chemotherapy was based on CheckMate -649, randomized, multicenter, open-label Phase 3 trial. The trial enrolled patients with previously untreated advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma and excluded patients who were known human epidermal growth factor receptor 2 (HER2) positive, or had untreated CNS metastases. In the trial, patients were randomized to receive Opdivo in combination with chemotherapy (patients with PD-L1 CPS ≥ 5: n=473; all randomized patients: n=789) or chemotherapy alone (patients with PD-L1 CPS ≥ 5: n=482; all randomized patients: n=792). Patients received one of the following treatments: Opdivo 240 mg in combination with mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) every two weeks or mFOLFOX6 every two weeks; or Opdivo 360 mg in combination with CapeOX (capecitabine and oxaliplatin) every three weeks or CapeOX every three weeks. Patients were treated until disease progression, unacceptable toxicity, or up to two years. Opdivo plus chemotherapy demonstrated superior overall survival (OS) compared to chemotherapy alone, both in all randomized patients, as well as in patients with PD-L1 combined positive score. In an exploratory analysis of all patients, 55% of patients on Opdivo in combination with chemotherapy were alive at one year versus 48% of patients on chemotherapy alone. Median PFS was 7.7 months in the nivolumab plus chemotherapy arm versus 6.0 months in the chemotherapy alone arm. As an additional efficacy outcome measure, a statistically significant improvement in OS was also demonstrated for all randomized patients (n=1,581) irrespective of CPS, with a median OS of 13.8 months in the nivolumab plus chemotherapy arm vs. 11.6 months in the chemotherapy alone arm.

Indication 12 - adult patients with resectable non-small cell lung cancer (NSCLC) in the neoadjuvant setting

approved March of 2022

Dosing/Administration

Opdivo 360 mg plus histology-based platinum doublet chemotherapy on the same day every three weeks for up to three cycles

Clinical Trial Results

FDA approval was based on CheckMate -816, a randomized, open label trial evaluating Opdivo plus platinum-doublet chemotherapy compared to chemotherapy alone as neoadjuvant treatment in adult patients with resectable non-small cell lung cancer, regardless of PD-L1 expression. For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy on the same day every three weeks for up to three cycles, or platinum doublet chemotherapy every three weeks for up to three cycles, followed by surgery. 

In the trial, when given before surgery, Opdivo plus chemotherapy showed a statistically significant improvement in Event Free Survival (EFS) with a 37% reduction in the risk of progression, recurrence or death compared to chemotherapy alone.Opdivo plus chemotherapy showed a median EFS of 31.6 months compared to 20.8 months for patients treated with chemotherapy alone. Additionally, 24% of patients treated with Opdivo plus chemotherapy achieved pathologic complete response (pCR) compared to 2.2% of patients treated with chemotherapy alone.