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G. Kollia
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MO18 - NSCLC - Targeted Therapies IV (ID 116)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:L. Horn, J. Wolf
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside Auditorium B, Level 1
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MO18.03 - Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with non-small cell lung cancer (NSCLC): overall survival and long-term safety in a phase 1 trial (ID 2356)
16:15 - 17:45 | Author(s): G. Kollia
- Abstract
- Presentation
Background
Blockade of programmed death-1 (PD-1), a co-inhibitory receptor expressed by activated T cells, can overcome immune resistance and mediate tumor regression (Topalian S, et al. New Engl J Med. 2012;366:2443-54). We present long-term safety and efficacy outcomes from a phase 1 study of nivolumab, a fully human IgG4 PD-1 receptor blocking monoclonal antibody, in patients with advanced NSCLC.Methods
NSCLC patients enrolled between 2008–2012 received nivolumab 1, 3, and 10 mg/kg IV Q2W on either dose escalation or subsequent expansion cohorts. Tumors were assessed (RECIST 1.0) after each 4-dose cycle. Protocol was amended (Jan. 23, 2012) to explore nivolumab’s potential to deliver prolonged overall survival (OS) for the initial and expansion cohorts and the overall population.Results
129 pretreated NSCLC patients (non-squamous [n=74], squamous [n=54], unknown histology [n=1]) were treated as of March 2013. Responses (CR/PR) occurred in 22 patients (17%) and were durable (estimated median response duration, 74.0 weeks [6.1+, 133.9+]), and ongoing in 55% (12/22) of patients. The highest objective response rate (ORR) was at 3 mg/kg (24%) across NSCLC histologies. Responses were rapid; 50% of patients (11/22) demonstrated response at first tumor assessment (8 weeks). Among 12 responders who discontinued therapy for reasons other than disease progression, 3 responded for ≥24 weeks post therapy discontinuation, and all 3 had not progressed at the time of this analysis. An additional 6 of the 122 patients (5%) demonstrated unconventional “immune-related” responses (based on target lesions), but were not included among responders. Survival benefit was demonstrated by 1-year and 2-year landmark OS rates (42% and 14%; Table). Median OS was 9.6 months across doses and 14.9 months at 3 mg/kg across histologies. Median OS across doses was similar for squamous/non-squamous patients. Any grade drug-related select adverse events (AEs) occurred in 41% (53/129) of patients (grade 3/4 select AEs, 5% [6/129]); most common being skin (16%), gastrointestinal (12%), and pulmonary (7%). Any grade drug-related pneumonitis occurred in 6% (8/129) of patients (grade 3/4 pneumonitis, 2% [3/129]), resulting in 2 deaths early in the trial, leading to increased emphasis on management algorithms. Characteristics and management of nivolumab-related pneumonitis will be summarized.Cohort Dose, mg/kg ORR[a] no. of patients/total no. of patients (%) [95% CI] Estimated median response duration, wk (range) Median OS,[b] mo (95% CI) OS rate, % (95% CI); patients at risk, n 1 y 2 y NSCLC (n=129)[c] All doses 22/129 (17.1) [11.0, 24.7] 74.0 (6.1+, 133.9+) 9.6 (7.8, 12.4) 42 (33, 51); 43 14 (4, 24); 5 1 1/33 (3.0) [0.1, 15.8] 63.9 (63.9, 63.9) 9.2 (5.6, 11.1) 3 9/37 (24.3) [11.8, 41.2] NR (16.1+, 133.9+) 14.9 (9.5, NE) 10 12/59 (20.3) [11.0, 32.8] 83.1 (6.1+, 117.1+) 9.2 (5.2, 12.4) Initial cohort (n=19) All doses 9.6 (4.5, 19.8) 42 (20, 64); 8 26 (7, 46); 5 Expansion cohort (n=110) All doses 9.9 (7.8, 12.5) 42 (32, 51); 35 Squamous (n=54) All doses 9/54 (16.7) [7.9, 29.3] NR (16.1, 133.9+) 9.2 (7.3, 12.5) 39 (25, 53); 16 1 0/15 0 8.0 (2.6, 13.3) 3 4/18 (22.2) [6.4, 47.6] NR (16.1, 133.9+) 9.5 (6.7, NE) 10 5/21 (23.8) [8.2, 47.2] 83.1 (16.1, 117+) 10.5 (7.8, 12.5) Non-squamous (n=74) All doses 13/74 (17.6) [9.7, 28.2] 63.9 (6.1+, 74.0+) 10.1 (7.2, 13.7) 43 (31, 54); 26 1 1/18 (5.6) [0.1, 27.3] 63.9 (63.9, 63.9) 9.9 (5.6, 22.7) 3 5/19 (26.3) [9.1, 51.2] 74.0 (24.3, 74.0+) 18.2 (10.3, 18.2) 10 7/37 (18.9) [8.0, 35.2] NR (6.1+, 65.7+) 7.4 (4.6, 12.4) [a]ORR = ([CR + PR] ÷ n) × 100.[b]OS estimates after 1 year reflect censoring and shorter follow-up for patients enrolling later in the study.[c]Non-squamous (n=74), squamous (n=54), and unknown histology (n=1) NE = not estimable; NR = not reached. Conclusion
In advanced NSCLC patients, nivolumab produced durable responses and survival benefit (1-year OS rate, 42%), with a long-term safety profile acceptable for the outpatient setting, supporting ongoing development in phase 3 trials with survival endpoints. Additional follow-up on patient survival will be presented at the time of the meeting.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.11-038 - Efficacy of nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with previously treated advanced non-small cell lung cancer (NSCLC): subpopulation response analysis in a phase 1 trial (ID 2751)
09:30 - 16:30 | Author(s): G. Kollia
- Abstract
Background
Lung cancer is the leading cause of cancer deaths globally, and NSCLC comprises 85% of lung cancers. Patients with advanced (stage IIIB or IV) NSCLC have a poor prognosis. Current second-line chemotherapeutics demonstrate a median overall survival (OS) of 8 months and 1-year survival of 30%. Factors that may influence clinical activity include age, ECOG performance status (PS), number of prior therapies, and EGFR- and KRAS-mutation status. The immune checkpoint receptor programmed death-1 (PD-1) negatively regulates T-cell activation upon interaction with its ligands PD-L1 and PD-L2. Nivolumab, a fully human IgG4, PD-1 receptor blocking monoclonal antibody, was evaluated in a phase 1 study (CA209-003; NCT00730639) in patients with various tumors, including previously treated advanced NSCLC. In this study, treatment with nivolumab demonstrated durable objective responses and prolonged stable disease in a portion of patients from this NSCLC cohort (Topalian S, et al. N Engl J Med. 2012;366:2443-54). We present the updated findings from assessment of clinical activity to nivolumab in subpopulations of the NSCLC cohort from this study.Methods
Patients received nivolumab (1–10 mg/kg IV Q2W) for ≤12 cycles (4 doses/8W cycle) or until discontinuation criteria were met. An analysis of clinical activity by select patient characteristics was performed from the NSCLC cohort of this trial.Results
129 patients with NSCLC (non-squamous [n=74], squamous [n=54], unknown histology [n=1]) received nivolumab at 1, 3, or 10 mg/kg as of March 2013 (Table). Association of clinical activity with baseline characteristics will be assessed for the following subgroups: age ≥70 and <70 years, gender, ECOG PS 0 and ≥1, number of prior therapies 1–2 and ≥3, prior tyrosine kinase inhibitor (TKI) therapy, EGFR-mutation status, and KRAS-mutation status.Table
Baseline characteristic[a] NSCLC patient population (n=129) Median age (range), y 65 (38–85) Gender, n (%) Male 79 (61) Female 50 (39) ECOG PS, n (%) 0 27 (21) 1 100 (78) 2 2 (2) Number of prior therapies, n (%) 1 25 (19) 2 34 (26) 3 27 (21) ≥4 43 (33) Prior therapy, n (%) Platinum-based chemotherapy 128 (99) TKI 36 (28) [a]Data on EGFR- and KRAS-mutation status are pending. Conclusion
Nivolumab demonstrated encouraging clinical activity in patients with previously treated advanced NSCLC. Clinical activity by patient subgroups may provide insights into the influence of patient and tumor characteristics on response to nivolumab. An update of the data regarding clinical activity of nivolumab therapy in these subgroups of the NSCLC cohort will be presented.
