Search

We characterized the safety of first-line nivolumab plus ipilimumab (NIVO+IPI) in a large patient population with metastatic NSCLC and efficacy outcomes after NIVO+IPI discontinuation owing to treatment-related adverse events (TRAEs).We pooled data from three first-line NIVO+IPI studies (NIVO, 3 mg/kg or 240 mg every 2 wk; IPI, 1 mg/kg every 6 wk) in metastatic NSCLC (CheckMate 227 part 1, CheckMate 817 cohort A, CheckMate 568 part 1). Safety end points included TRAEs and immune-mediated adverse events (IMAEs) in the pooled population and patients aged 75 years or older.In the pooled population (N = 1255), any-grade TRAEs occurred in 78% of the patients, grade 3 or 4 TRAEs in 34%, and discontinuation of any regimen component owing to TRAEs in 21%. The most frequent TRAE and IMAE were diarrhea (20%; grade 3 or 4, 2%) and rash (17%; grade 3 or 4, 3%), respectively. The most common grade 3 or 4 IMAEs were hepatitis (5%) and diarrhea/colitis and pneumonitis (4% each). Pneumonitis was the most common cause of treatment-related death (5 of 16). Safety in patients aged 75 years or older (n = 174) was generally similar to the overall population, but discontinuation of any regimen component owing to TRAEs was more common (29%). In patients discontinuing NIVO+IPI owing to TRAEs (n = 225), 3-year overall survival was 50% (95% confidence interval: 42.6-56.0), and 42% (31.2-52.4) of 130 responders remained in response 2 years after discontinuation.First-line NIVO+IPI was well tolerated in this large population with metastatic NSCLC and in patients aged 75 years or older. Discontinuation owing to TRAEs did not reduce long-term survival.

Introduction CheckMate 153 (NCT02066636) is a phase 3B/4 study assessing nivolumab in previously treated patients with advanced NSCLC. Eligibility criteria allowed enrollment of patients with poor prognostic features of advanced age or diminished Eastern Cooperative Oncology Group performance status (ECOG PS), which are typically underrepresented in or excluded from randomized controlled trials. Methods Patients with stage IIIB or IV NSCLC and an ECOG PS of 0 to 2 with disease progression after at least one systemic therapy received nivolumab (3 mg/kg every 2 weeks) until progression, unacceptable toxicity, or consent withdrawal. The primary end point was the incidence of grade 3 to 5 select treatment-related adverse events (TRAEs). Results Among 1426 treated patients, 556 (39%) were aged 70 years or older and 128 (9%) had an ECOG PS of 2. The median treatment duration was 3.2 months. Across subgroups and the overall population, the incidences of select grade 3 to 5 TRAEs (6%–9%) and grade 3 or 4 TRAEs (12%–14%) were similar. One grade 5 TRAE was documented. The median overall survival time was comparable in the overall population (9.1 months) and patients aged 70 years or older (10.3 months) but shorter in patients with an ECOG PS of 2 (4.0 months). Patient-reported outcomes generally improved. Conclusions Data from this large predominantly community-based study, which included patients aged 70 years or older and with an ECOG PS of 2, are consistent with registrational studies. As expected, the median overall survival for patients with an ECOG PS of 2 was lower than for the overall population but comparable with historical data.

PURPOSE Limited data exist on the optimal duration of immunotherapy, including for non–small-cell lung cancer (NSCLC). We present an exploratory analysis of CheckMate 153, a largely community-based phase IIIb/IV study, to evaluate the impact of 1-year fixed-duration versus continuous therapy on the efficacy and safety of nivolumab. METHODS Patients with previously treated advanced NSCLC received nivolumab monotherapy (3 mg/kg every 2 weeks). Those still receiving treatment at 1 year, including patients perceived to be deriving benefit despite radiographic progression, were randomly assigned to continue nivolumab until disease progression or unacceptable toxicity or to stop nivolumab with the option of on-study retreatment after disease progression (1-year fixed duration). RESULTS Of 1,428 patients treated, 252 were randomly assigned to continuous (n = 127) or 1-year fixed-duration (n = 125) treatment (intent-to-treat [ITT] population). Of these, 89 and 85 patients in the continuous and 1-year fixed-duration arms, respectively, had not progressed (progression-free survival [PFS] population). With minimum post–random assignment follow-up of 13.5 months, median PFS was longer with continuous versus 1-year fixed-duration treatment (PFS population: 24.7 months v 9.4 months; hazard ratio [HR], 0.56 [95% CI, 0.37 to 0.84]). Median overall survival from random assignment was longer with continuous versus 1-year fixed-duration treatment in the PFS (not reached v 32.5 months; HR, 0.61 [95% CI, 0.37 to 0.99]) and ITT (not reached v 28.8 months; HR, 0.62 [95% CI, 0.42 to 0.92]) populations. Few new-onset treatment-related adverse events occurred. No new safety signals were identified. CONCLUSION To our knowledge, these findings from an exploratory analysis represent the first randomized data on continuous versus fixed-duration immunotherapy in previously treated advanced NSCLC and suggest that continuing nivolumab beyond 1 year improves outcomes.

Nivolumab has been administered using a 60-min infusion time. Reducing this time to 30 min would benefit both patients and infusion facilities. This analysis compared the safety of 30- and 60-min infusions of nivolumab in patients with previously treated advanced non-small cell lung cancer. CheckMate 153 is an open-label, phase 3b/4, predominantly community-based study ongoing in the United States and Canada. Patients with stage IIIB/IV disease with progression/recurrence after at least one prior systemic therapy received nivolumab 3 mg/kg every 2 weeks over 30 or 60 min for 1 year or until disease progression. The primary outcome overall was to estimate the incidence of grade 3–5 treatment-related select adverse events; a retrospective objective was to estimate the incidence of hypersensitivity/infusion-related reactions (IRRs) with the 30-min infusion. Exploratory pharmacokinetic analyses were performed using a population pharmacokinetics model. Of 1420 patients enrolled, 369 received only 30-min infusions and 368 received only 60-min infusions. Similar frequencies of hypersensitivity/IRRs were noted in patients receiving 30-min [2% (n = 8)] and 60-min [2% (n = 7)] infusions. Grade 3–4 treatment-related hypersensitivity/IRRs led to treatment discontinuation in

TPS9076 Background: Although surgery for early NSCLC is potentially curative, 5-year overall survival (OS) rates for patients with stage IIA–IIIB disease are historically < 50%, representing a population of high unmet need. Conventional neoadjuvant or adjuvant chemo provides only a 5% absolute improvement in OS at 5 years. A rational approach to improve survival in these patients is to eradicate micrometastatic disease and potentially induce anti-tumor immunity to minimize the risk of relapse with peri-operative regimens including NIVO, a fully human anti–programmed death receptor-1 antibody. Early phase trials indicate that NIVO-based regimens have the potential to deepen pathological responses and extend survival in this setting (Reuss JE et al. Poster presentation at ASCO 2019. Abstract 8524; Cascone T et al. Oral presentation at ASCO 2019. Abstract 8504; Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). Data from the phase 2 single-arm NADIM trial (NCT03081689) demonstrated the highly encouraging major pathological response (MPR) rate of 83% with neoadjuvant NIVO plus chemo followed by adjuvant NIVO in patients with resectable stage IIIA NSCLC (Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). These results require validation in a large randomized controlled study. CheckMate 77T (NCT04025879) is a phase 3, randomized, double-blind trial evaluating neoadjuvant NIVO plus chemo followed by adjuvant NIVO in resectable early stage NSCLC. Methods: Approximately 452 patients aged ≥ 18 years with resectable stage IIA–IIIB (T3N2 only) NSCLC, ECOG performance status 0–1, and available lung tumor tissue will be enrolled at 113 sites in North America, South America, Europe, Asia, and Australia. Patients with EGFR/ALK mutations, brain metastasis, prior systemic anti-cancer treatment or radiotherapy, and autoimmune disease are excluded. Patients will be randomized to receive neoadjuvant NIVO plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant NIVO, or neoadjuvant placebo plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant placebo. The primary endpoint is event-free survival, assessed by blinded independent central review. Secondary endpoints include OS, pathological complete response and MPR assessed by blind independent pathological review, safety and tolerability. The start date was September 2019. The estimated primary completion date is May 2023. Clinical trial information: NCT04025879.

414 Background: Nivolumab has shown efficacy and acceptable safety in 2 open-label, multicenter studies (CheckMate 032 and 275) and is approved for patients (pts) with metastatic urothelial carcinoma (mUC) after ≥1 platinum-based therapy. Here we report longer-term efficacy and safety results for pts with mUC in the phase 1/2 CheckMate 032 study who received nivolumab monotherapy based on > 2 years of follow-up. Methods: Pts with mUC, regardless of programmed death-1 ligand 1 (PD-L1) expression status, received nivolumab 3 mg/kg intravenously every 2 weeks until progression or discontinuation. Tumor PD-L1 membrane expression was assessed with Dako PD-L1 immunohistochemical staining. Primary endpoint: objective response rate (ORR; RECIST 1.1); other endpoints: safety, progression-free survival (PFS), overall survival (OS), and duration of response. Results: Of 78 treated pts (median age 65.5 years; range, 31-85), 52 (66.7%) had received ≥2 prior therapies. At a minimum follow-up of 24 months, 11 pts (14.1%) remain on treatment. Treatment discontinuation was mainly due to disease progression (52 pts [66.7%]). Tumor PD-L1 expression was evaluable in 68 pts (87.2%); 26 (38.2%) pts had ≥1% and 42 (61.8%) had < 1% expression. The table shows overall efficacy. Updated ORR was 25.6%, with 1 additional complete response (CR) achieved for a CR rate of 8%. Median duration of response was not reached. ORR, 1- and 2-year PFS and OS rates were similar between the PD-L1 < 1% and > 1% subsets. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 22 pts (28.2%); most frequent were ↑lipase (6.4%), ↑amylase (5.1%), and maculopapular rash (3.8%). One pt had a grade 5 TRAE (pneumonitis). Conclusions: Nivolumab showed clinically meaningful, durable efficacy with promising long-term survival regardless of PD-L1 expression, and no new toxicity signals with longer-term follow-up in previously treated pts with mUC. Clinical trial information: NCT01928394. [Table: see text]

3059Background: Nivolumab,aprogrammed death-1 (PD-1) immune checkpoint inhibitor, is approved in the US for previously treated metastatic NSCLC and renal cell carcinoma, and for advanced melanoma, ...