FDA Approves Nivolumab Plus Ipilimumab with Chemotherapy for NSCLC

May 27, 2020

The FDA approved the use of nivolumab plus ipilimumab given with 2 cycles of platinum-doublet chemotherapy as a first-line treatment for adult patients with metastatic or recurrent non-small cell lung cancer.

The FDA has approved the use of nivolumab (Opdivo) plus ipilimumab (Yervoy) given with 2 cycles of platinum-doublet chemotherapy as a first-line treatment for adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations, according to Bristol Myers Squibb, the developer of the agents.  

The therapy has been approved for patients with squamous or non-squamous disease, regardless of PD-L1 expression. 

Previously on May 15, the FDA approved the combination as a first-line treatment for certain patients with metastatic NSCLC whose tumors express PD-L1 ≥ 1% as determined by an FDA-approved test. 

“Non-small cell lung cancer is a complex disease that requires multiple treatment options to address the needs of different patient populations,” Adam Lenkowsky, general manager and head of Oncology, Immunology, and Cardiovascular in the Bristol Myers Squibb US branch, said in a press release. “This second approval of an (nivolumab and ipilimumab)-based combination for the first-line treatment of advanced NSCLC now gives more patients access to a dual immunotherapy approach that can be administered with or without limited chemotherapy, depending on the patient and their PD-L1 status, and the possibility of a chance to live longer.”

Approval for the combination with limited chemotherapy was based on the pre-specified interim analysis from the randomized, open-label, multi-center, phase III CheckMate-9LA trial, which was designed to evaluate nivolumab plus ipilimumab combined with 2 cycles of platinum-doublet chemotherapy versus platinum-doublet chemotherapy (4 cycles followed by optional pemetrexed maintenance therapy if eligible) as a first-line treatment in patients with metastatic or recurrent NSCLC, regardless of PD-L1 and histology. 

Overall, a total of 361 patients with treated with the combination and platinum-doublet chemotherapy until disease progression, unacceptable toxicity, or for up to 2 years. Patients were given 360 mg of nivolumab plus 1 mg/kg (injections for intravenous use) of ipilimumab given with 2 cycles of platinum-doublet chemotherapy. 

A total of 358 patients were treated with platinum-doublet chemotherapy for 4 cycles and optional pemetrexed maintenance for non-squamous patients (if eligible) until disease progression or toxicity.

The primary outcome for the trial was overall survival (OS). Additional outcome measures included progression-free survival (PFS), overall response rate (ORR), and duration of response as assessed by Blinded Independent Central Review (BICR). 

The trial found that nivolumab plus ipilimumab combined with 2 cycles of platinum-doublet chemotherapy demonstrated superior OS versus chemotherapy alone (HR, 0.69; 96.71% CI, 0.55-0.87; P = 0.0006), regardless of PD-L1 expression or tumor histology. 

Moreover, median OS was 14.1 months (95% CI, 13.2-16.2) versus 10.7 months (95% CI, 9.5-12.5), respectively. In a follow-up analysis at 12.7 months, the hazard ratio improved numerically to 0.66 (95% CI, 0.55-0.80), with a median OS of 15.6 months (95% CI, 13.9-20.0) and 10.9 months (95% CI, 9.5-12.5). 

At 1 year, 63% of patients treated with nivolumab plus ipilimumab with limited chemotherapy and 47% of those treated with only chemotherapy were still alive. 

“We have come a long way in understanding the role of dual immunotherapy-based approaches in cancer and the potential impact on patients’ long-term outcomes,” David P. Carbone, MD, PhD, CheckMate-9LA investigator and director of the James Thoracic Oncology Center at The Ohio State University, said in the release. “The positive findings from CheckMate-9LA demonstrate the benefit of combining dual immunotherapy with limited chemotherapy for NSCLC patients regardless of PD-L1 status. With today’s approval, more patients now have access to an (nivolumab plus ipilimumab)-based option and a chance at a longer life.”

In the trial, the ORR per BICR was 38% (95% CI, 33-43) for patients treated with nivolumab plus ipilimumab with limited chemotherapy and 25% (95% CI, 21-30) for patients treated with chemotherapy. 

Notably, serious adverse events (AEs) occurred in 57% of patients. Nivolumab plus ipilimumab in combination with platinum-doublet chemotherapy were discontinued for AEs in 24% of patients and 56% had at least 1 treatment withheld for an AE. 

The most frequent serious AEs were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure. Further, fatal AEs occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia. The most common AEs were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased appetite (28%), constipation (21%), and pruritus (21%).

“Receiving a diagnosis of advanced lung cancer is devastating,” Andrea Ferris, president and chief executive officer of LUNGevity, said in a press release. “Today’s announcement is welcome news as it provides a new dual immunotherapy-based option for previously untreated patients searching for a treatment that may help extend their lives.”

Reference:

U.S. Food and Drug Administration Approves Opdivo® (nivolumab) + Yervoy® (ipilimumab) Combined with Limited Chemotherapy as First-Line Treatment of Metastatic or Recurrent Non-Small Cell Lung Cancer [news release]. Princeton, NJ. Published May 26, 2020. news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-approves-opdivo-nivolumab-ye-2. Accessed May 27, 2020.