CHECKMATE 227: IN A CROSS-HISTOLOGY TRIAL FOR PATIENTS WITH mNSCLC
(PD-L1 ≥1%)

Durable survival with OPDIVO® + YERVOY®:
29% of patients alive at 4 years2*

Dual I-O Durability
A chance for
durable survival

OS FOR PD-L1 ≥1%
(EXTENDED FOLLOW-UP ANALYSIS)1-3

Checkmate 227 OS with OPDIVO® (nivolumab) + YERVOY® (ipilimumab) in mNSCLC Patients at 3.5 Years, Chart Checkmate 227 OS with OPDIVO® (nivolumab) + YERVOY® (ipilimumab) in mNSCLC Patients at 3.5 Years, Chart

Median follow-up of 54.8 months.2

  • Median PFS with a minimum follow-up of 54.8 months: 5.1 months (95% CI: 4.1–6.3) with OPDIVO + YERVOY and 5.6 months (95% CI: 4.6–5.8) with chemo alone; HR=0.81 (95% CI: 0.68-0.96)1,2†
  • 29% of patients enrolled had SQ disease; 71% had NSQ disease1
  • ORR with a median follow-up of 54.8 months: 36% (144/396; CR=6.3%; PR=30.1%) with OPDIVO + YERVOY and 30% (119/397; CR=1.8%; PR=28.2%) with chemo2,4
    • Median TTR, with a median follow-up of 54.8 months, was 2.4 months with OPDIVO + YERVOY and 1.6 months with chemo4

The only I-O combination with mDOR of 23.2 months among responders2

ORR with a median follow-up of 54.8 months: 36% (144/396) with OPDIVO + YERVOY and 30% (119/397) with chemo2,4

*

vs chemo. In Checkmate 227, patients in the comparator arm received up to 4 cycles of platinum-doublet chemo q3w; NSQ: pemetrexed + carboplatin or cisplatin, with optional pemetrexed maintenance following chemo; SQ: gemcitabine + carboplatin or cisplatin.1,5

In Checkmate 227 Part 1a, PFS, ORR, and DOR were pre-specified descriptive analyses. The primary efficacy outcome measure was OS.1

Study design: Checkmate 227 was a randomized, open-label, phase 3 trial in patients with metastatic or recurrent NSCLC. Key eligibility criteria included patients 18 years or older, stage IV or recurrent NSCLC, ECOG PS 0/1, and no prior systemic anticancer therapy. Patients with known EGFR mutations or ALK translocations sensitive to available targeted inhibitor therapy, untreated brain metastases, carcinomatous meningitis, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded from the study. Treatment continued until disease progression, unacceptable toxicity, or for up to 24 months. Tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory. In Part 1a (n=793), patients with PD-L1 ≥1% were randomized to either OPDIVO 3 mg/kg q2w + YERVOY 1 mg/kg q6w (n=396) or platinum-doublet chemotherapy* (n=397). The primary endpoint in Part 1a was OS in patients with PD-L1 ≥1%. Pre-specified descriptive efficacy outcome measures included PFS, ORR, and DOR.1

*

In Checkmate 227, patients in the comparator arm received up to 4 cycles of platinum-doublet chemo q3w; NSQ: pemetrexed + carboplatin or cisplatin, with optional pemetrexed maintenance following chemo; SQ: gemcitabine + carboplatin or cisplatin.1,5

1L=first-line; ALK=anaplastic lymphoma kinase; CI=confidence interval; CR=complete response; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group Performance Status; EGFR=epidermal growth factor receptor; HR=hazard ratio; IHC=immunohistochemistry; I-O=immuno-oncology; mDOR=median duration of response; mos=months; mNSCLC=metastatic non-small cell lung cancer; NSCLC=non-small cell lung cancer; NSQ=non-squamous; ORR=overall response rate; OS=overall survival; PD-L1=programmed death-ligand 1; PFS=progression-free survival; PR=partial response; q2w=every 2 weeks; q6w=every 6 weeks; SQ=squamous; TTR=time to response.

Select Important Safety Information

Serious Adverse Reactions

In Checkmate 227, serious adverse reactions occurred in 58% of patients (n=576). The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure.

Common Adverse Reactions

In Checkmate 227, the most common (≥20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%).

Please see additional Important Safety Information below.

Among OPDIVO + YERVOY responders at 6 months, 70% were alive at 3.5 years (post-randomization)6*

OS (PD-L1 ≥1%) IN RESPONDERS (CR/PR) AT 6 MONTHS (POST-HOC EXPLORATORY LANDMARK ANALYSIS)6,7

  • This is a post-hoc, exploratory, conditional landmark analysis where patients were grouped by response category based on assessment at 6 months6†
    • A conditional landmark analysis can minimize potential guarantee time bias when the time to response may be different between arms or when comparing responding patients and non-responding patients
    • No formal statistical testing was planned for this and, therefore, no statistical conclusions can be drawn
    • The 6-month time point was chosen because it is the earliest time point when most of the responses in each treatment arm had occurred
    • An important limitation of this analysis is that responding patients who died before 6 months were not included

Minimum follow-up for post-landmark OS: 31.7 months.1

  • 6 months post-randomization was the landmark6
    • 1 year post-landmark was conducted at 18 months
    • 2 years post-landmark was conducted at 30 months
    • 3 years post-landmark was conducted at 42 months
  • In Checkmate 227 Part 1a, PFS, ORR, and DOR were pre-specified descriptive analyses. The primary efficacy outcome measure was OS1
  • ORR: 36% (144/396; 95% CI: 32-41; CR=5.8%) with OPDIVO + YERVOY and 30% (119/397; 95% CI: 26-35; CR=1.8% with chemo2,3,7

*

Post-randomization: Time point measurement starting from treatment initiation (month 0).2

Response categories based on information at 6 months are different from best overall response, which was based on all data from study follow-up.2

NR=not reached.

National Comprehensive Cancer Network® (NCCN®)
Category 1 Recommended8

NIVOLUMAB (OPDIVO) +
IPILIMUMAB (YERVOY)

NCCN Category 1, useful in certain circumstances

  • Nivolumab (OPDIVO) + ipilimumab (YERVOY) is recommended as a Category 1, useful in certain circumstances, first-line therapy option for eligible patients with metastatic NSCLC with PD-L1 ≥1% and performance status 0-2 (V5.2021), in tumors that are EGFR, ALK, ROS1, BRAF V600E, NTRK1/2/3, METex14, and RET negative, and no contraindications to PD-1 or PD-L1 inhibitors8

Please see updated NCCN Guidelines for a complete listing of all NCCN-recommended agents, including preferred options. NCCN makes no warranties of any kind whatsoever regarding their content, use of the application and disclaims any responsibility for their application or use in any way.

PD-1=programmed death receptor-1; r/m=recurrent or metastatic.

OPDIVO + YERVOY dosing1

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Continuous Dosing Schedule OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Continuous Dosing Schedule
  • OPDIVO is administered as an IV infusion over 30 minutes1
  • YERVOY is administered as an IV infusion over 30 minutes9

IV=intravenous.