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FP13 - Immunotherapy (Phase II/III Trials) (ID 247)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP13.01 - 5-Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel in Previously Treated, PD-L1–Positive Advanced NSCLC (ID 1371)
00:00 - 00:00 | Author(s): Michael Boyer
- Abstract
- Presentation
Introduction
The KEYNOTE-010 study (NCT01905657) showed significantly improved OS with pembrolizumab 2 or 10 mg/kg Q3W versus docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1%. We provide long-term follow-up for KEYNOTE-010 including updated efficacy outcomes in patients who completed 35 cycles (2 years) of pembrolizumab and those who received second-course pembrolizumab.
Methods
Patients had previously treated advanced NSCLC with PD-L1 TPS ≥1% and were randomized 1:1:1 to receive pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W. Pembrolizumab treatment continued for 35 cycles (~2 years) or until disease progression/unacceptable toxicity. Eligible patients who completed pembrolizumab treatment or stopped pembrolizumab after achieving CR and receiving ≥6 months of treatment could receive second-course of pembrolizumab for up to 17 cycles (1 year) following disease progression after stopping pembrolizumab. Response was assessed Q9W. Survival was assessed every 2 months after treatment ended. Primary endpoints were OS and PFS in patients with PD-L1 TPS ≥50% and in those with PD-L1 TPS ≥1% (total population). Pembrolizumab in the pembrolizumab dose groups were pooled for this analysis.
Results
1033 patients were included in these analyses (pembrolizumab, 690; docetaxel, 343). As of April 8, 2020, median (range) time from randomization to data cutoff was 67.4 (60.0‒77.9) months. OS and PFS favored pembrolizumab in patients with PD-L1 TPS ≥50% and ≥1% (Table). Seventy-nine patients in the pembrolizumab group completed 35 cycles or 2 years of treatment with ORR of 98.7% (15 CR, 63 PR) in this group. Among those who completed 35 cycles or 2 years of pembrolizumab, 61 patients (77.2%) were alive (38 of whom were alive without PD). The 3-year OS rate after completing 35 cycles or 2 years (ie, at approximately 5 years) was 83.0%. Twenty-one patients received second-course pembrolizumab; 15 (71.4%) were alive at data cutoff. ORR after starting second-course was 52.4% (1 CR, 10 PR) and 6 had SD. Eight patients with CR/PR/SD after starting second-course subsequently had PD.
Table.
ConclusionPatients with PD-L1 TPS ≥50%
Patients With PD-L1 TPS ≥1%
Pembrolizumab
(N = 290)
Docetaxel
(N = 152)
Pembrolizumab
(N = 690)
Docetaxel
(N = 343)
Median OS,a mo (95% CI)
16.9 (12.3‒21.4)
8.2 (6.4‒9.8)
11.8 (10.4‒13.1)
8.4 (7.6‒9.5)
HR (95% CI)
0.55 (0.44‒0.69)
0.70 (0.61‒0.80)
5-year OS rate,a %
25.0
8.2
15.6
6.5
Median PFS,a,b mo (95% CI)
5.3 (4.2‒6.5)
4.2 (3.8‒5.1)
4.0 (3.1‒4.1)
4.1 (3.8‒4.5)
HR (95% CI)
0.57 (0.46‒0.71)
0.84 (0.73‒0.96)
5-year PFS rate,a %
18.2
Not reached
9.4
0.7
aKaplan-Meier estimate.
bAssessed by independent central review per RECIST version 1.1.
With more than 5 years of follow-up, pembrolizumab continued to provide clinically meaningful improvement in OS and PFS versus docetaxel in patients with previously treated, PD-L1–positive advanced NSCLC; 5-year OS rates were more than doubled in pembrolizumab-treated patients. Patients who completed 35 cycles or 2 years of pembrolizumab had durable clinical benefit. Second-course pembrolizumab provided meaningful disease control in the majority of patients who had disease progression after 2 years of pembrolizumab treatment.
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OA11 - A Symphony of Progress (ID 229)
- Event: WCLC 2020
- Type: Oral
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/31/2021, 15:30 - 16:30, Scientific Program Auditorium
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OA11.03 - A Phase 1 Study of AMG 757, Half-Life Extended Bispecific T-Cell Engager (BiTE®)Immune Therapy Against DLL3, in SCLC (ID 3414)
15:30 - 16:30 | Author(s): Michael Boyer
- Abstract
- Presentation
Introduction
Delta-like ligand 3 (DLL3), an inhibitory Notch ligand that is highly expressed in small cell lung cancer (SCLC) compared to normal tissues, is a potential therapeutic target.1 AMG 757, a half-life extended BiTE® immune therapy, binds DLL3 on tumor cells and CD3 on T cells, leading to T cell‑dependent killing of tumors. Emerging data from the ongoing phase 1 study of AMG 757 in SCLC are reported (NCT03319940).
Methods
AMG 757 (0.003–10.0 mg) was administered intravenously every two weeks with/without step dose. Eligible patients had SCLC that progressed or recurred following ≥1 platinum-based regimen. Antitumor activity was assessed using modified RECIST 1.1. Tumor DLL3 expression was assessed by immunohistochemistry. T-cell activation and cytokine profiles pre and post AMG 757 treatment were evaluated.
Results
As of 7 August 2020, 40 patients (median age [range], 64 years [44–80]; ECOG PS: 0-1, n=39 [97.5%], median prior lines: 2.0 [1–6]; prior PD-1/PD-L1 treatment: n=17 [42.5%]) enrolled at eight dose levels (DL) received ≥1 AMG 757 dose. Median treatment duration was 6.1 weeks (0.1–59.4). Adverse events occurred in 39 (97.5%) patients, resulting in discontinuation in 4 (10.0%); 32 (80.0%) were treatment-related, including 7 (17.5%) grade ≥3 and 1 (2.5%) grade 5 (pneumonitis; DL5 [0.3 mg]). Cytokine release syndrome (CRS) was reported in 18 (45.0%) patients; grade 2 CRS in 5 (12.5%); no grade ≥3 CRS. CRS presented mainly as fever ± hypotension, was reversible, did not lead to treatment interruption or discontinuation, occurred mostly within 24 hours of the first two doses of AMG 757, and was managed with supportive care, corticosteroids, and/or anti-IL-6 treatment. AMG 757 showed dose proportional increase in exposures.
Confirmed partial response (PR) was reported for 6 (15.8%) patients (1/12 [8.3%] in DL5, 1/8 [12.5%] in DL6, 3/7 [42.9%] in DL7, and 1/7 [14.3%] in DL8 [Figure]). Stable disease was reported for 11 (28.9%). One patient has ongoing unconfirmed PR in DL8. Evaluation of DL8 is ongoing. Patients with confirmed PR had a median of 2 (1–4) prior lines of therapy and duration of response of 1.9+ to 9.4+ months. DLL3 expression at any level was observed in 31/32 (96.9%) patient tumor samples, with overall H-score 40–300. Tumor shrinkage occurred across a wide range of DLL3 expression (H-score, 55–300).
Conclusion
AMG 757 has acceptable safety at doses of up to 10 mg and shows anti-tumor activity in patients with SCLC. Dose escalation is ongoing.
References
1. Leonetti A, et al. Cell Oncol (Dordr). 2019;42(3):261-273.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.03 - Efficacy and Safety of Capmatinib Plus Nivolumab in Pretreated Patients with EGFR Wild-Type Non–Small Cell Lung Cancer (ID 817)
00:00 - 00:00 | Author(s): Michael Boyer
- Abstract
Introduction
Dysregulation of the MET gene can be an oncogenic driver event in non-small cell lung cancer (NSCLC). Capmatinib is a highly potent and selective MET inhibitor. The results of the GEOMETRY mono-1 trial demonstrated efficacy of capmatinib in patients with locally advanced/metastatic METex14-mutated NSCLC (Wolf J. et al, ASCO 2019). In addition, MET was found to directly modulate immune cell function, leading to suppression of anti-cancer immune responses. Further, capmatinib was shown to enhance efficacy of cancer immunotherapy in mice models irrespective of the tumor MET status. Nivolumab is a programmed death receptor-1 inhibitor approved for metastatic NSCLC in patients who progressed after platinum-based chemotherapy. Combining a MET inhibitor with a PD-1 inhibitor may yield sustained clinical benefits in advanced NSCLC.
Methods
This phase 2 trial (NCT02323126) evaluated the efficacy and safety of capmatinib plus nivolumab in patients with advanced/metastatic EGFR wild-type NSCLC who had progressed on platinum-doublet therapy and were anti-PD-1/PD-L1 therapy-naïve. Patients received capmatinib 400 mg orally twice daily plus nivolumab 3 mg/kg intravenous every 2 weeks. Patients were grouped into high MET (immunohistochemistry [IHC]=3+ in ≥50% tumor cells [TCs] or IHC=2+ in ≥50% TCs and gene copy number (GCN)≥5 or METex14+) and low MET (all others) cohorts. The primary endpoint was progression-free survival (PFS) rate at 6 months using RECISTv1.1. Secondary endpoints included overall response rate, disease control rate, other PFS endpoints, 1-year overall survival (OS)-rate and safety.
Results
As of Sep 10, 2019, 46 patients (high MET [n=16] and low MET [n=30]) were enrolled from February 2015–April 2019; median age: 65 years; male: 50%; Stage IV: 93.5%; ECOG PS 0 or 1: 97.8%. At this preliminary data analysis (June 11, 2019), the 6 month-PFS rate (95% CI) was 60.7% (29.1%–81.7%) in the high MET and 41.7% (22.7%–59.6%) in the low MET cohorts, whereas 1-year-OS data was immature. The ORR (95% CI) was 25.0% (7.3%–52.4%) in the high MET cohort compared to 16.7% (5.6%–34.7%) in the low MET cohort. The DCR (95% CI) was 81.3% (54.4%–96.0%) and 43.3% (25.5%–62.6%) in the high MET and low MET cohorts, respectively. Twenty-nine PFS events were reported; high MET: 9 (56.3%) and low MET: 20 (66.7%). The median PFS (95% CI) was 13.8 (3.5–19.2) months in the high MET cohort versus 4.2 (1.8–7.6) months in the low MET cohort. Most frequent AEs (≥30%; any grade) were nausea (54.3%), vomiting (39.1%), increased amylase, asthenia, increased blood creatinine, and peripheral edema (32.6% each). Most frequent Grade 3/4 AEs (≥10%) were dyspnea and increased amylase (15.2% each) and increased lipase (10.9%). Dyspnea (10.9%), pyrexia (8.7%) and vomiting (6.5%) were most commonly reported serious AEs. Serious treatment-related AEs were reported in 23.9% patients, of which the most common were pyrexia and vomiting (6.5% each).
Conclusion
Capmatinib plus nivolumab showed clinical activity in pretreated patients with advanced/metastatic EGFR wild-type NSCLC with a manageable safety profile. While anti-tumor activity was evident in both high MET and low MET cohorts, 6 month-PFS-rate, ORR and DCR were numerically higher in patients with high MET tumors.
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P76.08 - High Tumour PD-L1 Is Associated With Poor Outcomes in EGFR-Mutant Lung Cancer Treated With First Generation EGFR TKIs (ID 951)
00:00 - 00:00 | Author(s): Michael Boyer
- Abstract
Introduction
Approximately 10% of patients with metastatic EGFR-mutant NSCLC exhibit de novo resistance to 1st generation tyrosine kinase inhibitors (TKIs). Apart from the upfront presence of resistance mutations such as T790M, there are no established predictive biomarkers for poor response to TKIs. It has been observed that high tumour PD-L1 expression is associated with poor response to EGFR TKIs in some but not all retrospective series. This study sought to determine the relationship between patients’ outcome treated with 1st line EGFR TKI, and baseline PD-L1 tumour proportional score (TPS) in a large multicentre retrospective series of patients with EGFR-mutant lung cancer.
Methods
Patients with Stage IIIB/IV lung adenocarcinoma harbouring a sensitising mutation in EGFR and treated with first-line, first or second generation TKI at five large metropolitan hospitals in Sydney between 2013-2019 were included. PD-L1 TPS was determined using the Ventana anti-PD-L1 (SP263) assay in a NATA-accredited laboratory on a pre-treatment biopsy. High PD-L1 expression is defined as TPS ≥50%; low expression TPS 1 – 49%; and negative PD-L1 TPS <1%. Clinico-pathological information was collected from institutional medical records, and treatment response, progression and survival were investigator-assessed. Determinants of progression and survival hazards were modelled using Cox regression with censoring at dates of last follow-up.
Results
Of the 168 included patients, mean age was 67 years, 66% female, and 46% of Caucasian ethnicity. Twenty-eight percent received 1st line gefitinib, 70% received erlotinib and 2% received afatanib. Compared to patients with PD-L1 low/negative tumours (n=145, 86%, those with high PD-L1 (n=23; 14%) had significantly shorter PFS (6.6 vs 13.0 months, HR 2.6 95% CI 1.6-4.2, p<0.0001) and OS (11.5 vs 32.9 months, HR 3.3, 95% CI 1.9-5.7, p<0.0001) and also on multivariate analyses after adjusting for age, ECOG, ethnicity, type of TKI, EGFR mutation type and metastatic sites (p<0.0001). PFS and OS were not significantly different in patients with PD-L1 positive tumours (≥1%) versus PD-L1 negative tumours. High PD-L1 in post-TKI progression biopsies was not associated with poorer outcome compared to low PD-L1 in post-progression biopsies.
Conclusion
In this large real-world cohort of patients with EGFR mutant NSCLC, high PD-L1 expression was associated with early resistance to 1st generation EGFR TKIs, and predicts shorter survival. Next generation sequencing of exceptional and poor responders with low vs high PD-L1 is underway to explore molecular mechanisms that may drive PD-L1 expression or non-response to TKIs.
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PL02 - Innovation to Bridge Lung Cancer Care Tomorrow (Japanese, Mandarin, Spanish Translation Available) (ID 141)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 07:00 - 09:00, Scientific Program Auditorium
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PL02.07 - Translational Medicine: An Engine of Change for Bringing New Technology to the Community (ID 3906)
07:00 - 09:00 | Presenting Author(s): Michael Boyer
- Abstract
- Presentation
Abstract
Translational medicine refers to the process of turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public − from diagnostics and therapeutics to medical procedures and behavioral changes1. The field of translational medicine developed in the late 1990’s and early 2000’s as a response to perceived shortcomings in the way in which biomedical research was being applied to create advances in human health2. In particular there was concern that there was over-emphasis on basic research with much less time, money and energy devoted to clinical research. Consequently the transfer of basic research findings into therapies that could improve outcomes for patients was slow, expensive and prone to failure.
At about the same time, powerful new technologies were being developed including genomics, proteomics, metabolomics, and advanced imaging, including functional imaging. These technologies resulted in human studies being able to bring novel information to the attention of basic scientists and reversed the traditional flow of bench to bedside research to become bedside to bench.
Recognition of these issue led to the development of a model for translational research that identified T1 and T2 research. T1 research encompasses bench to bedside research and emphasizes the bidirectional nature of this with clinical observations feeding back and influencing or even initiating basic laboratory research. It assists in the identification of how new knowledge of disease mechanisms can be developed into clinically relevant understandings, and includes laboratory research, phase I and II trials and observational and case studies.
T2 research focuses on testing the effectiveness of treatments and interventions by translating new science or knowledge into routine clinical practice. Typically this involves phase III trials, and the synthesis of evidence and guidelines.
There are many examples of successful translational medicine approaches within oncology in general and lung cancer specifically. Many biomarker driven therapies have arisen as a result of, and been refined by, translational research that has identified targets, and tested the technologies required in order to introduce these therapies. Although technologies can be developed outside of the clinical setting, translational research is required to assess their utility and define their role in clinical medicine.
The slow pace of introduction of proven beneficial treatments into routine clinical practice has been identified as a further obstacle to improvements in health outcomes3. This has led to the development of an additional type of translational research known as T3 research. The focus of T3 research is the identification of methods to facilitate the dissemination and implementation of standard therapies into practice. This address issues such as how evidence from clinical trials, which typically involve carefully selected patients, is translated into guidelines for the complex patients who are seen in routine clinical practice. It also focuses on unwarranted variation in practice.
Translational medicine has driven advances in clinical care for patients with lung cancer and is likely to continue as an important component underpinning the introduction of new technologies and their incorporation into routine clinical care of patients.
References
https://ncats.nih.gov/files/NCATS_Factsheet_508.pdf From National Centre for Advancing Translational Sciences. Accessed Dec 10, 2020
Crowley WF, Gusella JF. Changing models of biomedical research. Science Translational Medicine 2009; 1: 1 – 6
Westfall JM, Mold J, Fagnan L. Practice-based research: “Blue Highways” on the NIH Roadmap. JAMA 2007; 297: 403 - 406
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PS01 - Presidential Symposium (Japanese, Mandarin, Spanish Translation Available) (ID 143)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 07:00 - 09:00, Scientific Program Auditorium
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PS01.09 - Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo as 1L Therapy for Metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598 (ID 4248)
07:00 - 09:00 | Presenting Author(s): Michael Boyer
- Abstract
- Presentation
Introduction
In KEYNOTE-024, pembrolizumab monotherapy significantly improved survival versus platinum-doublet chemotherapy in patients with metastatic NSCLC with PD-L1 TPS ≥50% and no targetable EGFR or ALK aberrations. We conducted the randomized, double-blind, phase 3 KEYNOTE-598 study (NCT03302234) to determine whether adding ipilimumab to pembrolizumab improved efficacy over pembrolizumab alone in this population.
Methods
Eligible patients were randomized 1:1 to ipilimumab 1 mg/kg Q6W or saline placebo for up to 18 cycles; patients in both arms received pembrolizumab 200 mg Q3W for up to 35 cycles. Randomization was stratified by ECOG PS (0 vs 1), region (East Asia vs not East Asia), and histology (squamous vs nonsquamous). Treatment differences in the primary endpoints of OS and PFS (RECIST v1.1; blinded, independent central review) were assessed by the stratified log-rank test in the ITT population. The protocol-specified first interim analysis (IA1) was planned to occur when ~255 deaths occurred and ~12 months after the last participant was randomized. Nonbinding futility criteria at IA1 were differences in the restricted mean survival time (RMST) between pembro–ipi and pembro–placebo of ≤0.2 at the maximum observation time and ≤0.1 at 24 months of follow-up.
Results
Between 12‑January‑2018 and 22‑August‑2019, 568 participants were randomized to pembro–ipi (n=284; 282 treated) and pembro–placebo (n=284; 281 treated). As of 01‑September‑2020, median (range) study follow-up was 20.6 months (12.4-31.7), treatment was ongoing in 21.3% in the pembro–ipi arm vs 23.8% in the pembro–placebo arm, and median number of treatment cycles was 10 vs 15. Baseline characteristics were balanced between arms. With 272 deaths, median OS was 21.4 months for pembro–ipi vs 21.9 months for pembro–placebo (HR, 1.08 [95% CI, 0.85-1.37]; P = 0.74). RMST differences were –0.56 at the maximum observation time and –0.52 at 24 months, which met the futility criteria. With 372 events, median PFS was 8.2 months for pembro–ipi vs 8.4 months for pembro–placebo (HR, 1.06 [95% CI, 0.86-1.30]; P = 0.72). ORR was 45.4% in both arms; median DOR was 16.1 months for pembro–ipi vs 17.3 months for pembro–placebo. Treatment-related AEs occurred in 76.2% of pembro–ipi recipients vs 68.3% of pembro–placebo recipients, were of grade 3-5 in 35.1% vs 19.6%, led to death in 2.5% vs 0%, and led to discontinuation of any treatment in 25.2% vs 10.7%. Immune-mediated AEs and infusion reactions occurred in 44.7% of pembro–ipi recipients vs 32.4% of pembro–placebo recipients, were grade 3-5 in 20.2% vs 7.8%, led to death in 2.1% vs 0%, and led to discontinuation of any treatment in 14.9% vs 5.3%. Based on the observed efficacy and safety, the external data monitoring committee recommended that the study be stopped due to futility and that participants discontinue ipi/placebo.
Conclusion
Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab alone as first-line therapy for metastatic NSCLC with PD-L1 TPS ≥50% and no targetable EGFR or ALK aberrations. These data confirm pembrolizumab monotherapy as a standard-of-care for this population.
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PS02 - Presidential Symposium (Re-Broadcast) (Japanese, Mandarin, Spanish Translation Available) (ID 275)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 18:00 - 20:00, Scientific Program Auditorium
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PS02.09 - Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo as 1L Therapy for Metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598 (ID 4292)
18:00 - 20:00 | Presenting Author(s): Michael Boyer
- Abstract
Introduction
In KEYNOTE-024, pembrolizumab monotherapy significantly improved survival versus platinum-doublet chemotherapy in patients with metastatic NSCLC with PD-L1 TPS ≥50% and no targetable EGFR or ALK aberrations. We conducted the randomized, double-blind, phase 3 KEYNOTE-598 study (NCT03302234) to determine whether adding ipilimumab to pembrolizumab improved efficacy over pembrolizumab alone in this population. Methods
Eligible patients were randomized 1:1 to ipilimumab 1 mg/kg Q6W or saline placebo for up to 18 cycles; patients in both arms received pembrolizumab 200 mg Q3W for up to 35 cycles. Randomization was stratified by ECOG PS (0 vs 1), region (East Asia vs not East Asia), and histology (squamous vs nonsquamous). Treatment differences in the primary endpoints of OS and PFS (RECIST v1.1; blinded, independent central review) were assessed by the stratified log-rank test in the ITT population. The protocol-specified first interim analysis (IA1) was planned to occur when ~255 deaths occurred and ~12 months after the last participant was randomized. Nonbinding futility criteria at IA1 were differences in the restricted mean survival time (RMST) between pembro–ipi and pembro–placebo of ≤0.2 at the maximum observation time and ≤0.1 at 24 months of follow-up. Results
Between 12‑January‑2018 and 22‑August‑2019, 568 participants were randomized to pembro–ipi (n=284; 282 treated) and pembro–placebo (n=284; 281 treated). As of 01‑September‑2020, median (range) study follow-up was 20.6 months (12.4-31.7), treatment was ongoing in 21.3% in the pembro–ipi arm vs 23.8% in the pembro–placebo arm, and median number of treatment cycles was 10 vs 15. Baseline characteristics were balanced between arms. With 272 deaths, median OS was 21.4 months for pembro–ipi vs 21.9 months for pembro–placebo (HR, 1.08 [95% CI, 0.85-1.37]; P = 0.74). RMST differences were –0.56 at the maximum observation time and –0.52 at 24 months, which met the futility criteria. With 372 events, median PFS was 8.2 months for pembro–ipi vs 8.4 months for pembro–placebo (HR, 1.06 [95% CI, 0.86-1.30]; P = 0.72). ORR was 45.4% in both arms; median DOR was 16.1 months for pembro–ipi vs 17.3 months for pembro–placebo. Treatment-related AEs occurred in 76.2% of pembro–ipi recipients vs 68.3% of pembro–placebo recipients, were of grade 3-5 in 35.1% vs 19.6%, led to death in 2.5% vs 0%, and led to discontinuation of any treatment in 25.2% vs 10.7%. Immune-mediated AEs and infusion reactions occurred in 44.7% of pembro–ipi recipients vs 32.4% of pembro–placebo recipients, were grade 3-5 in 20.2% vs 7.8%, led to death in 2.1% vs 0%, and led to discontinuation of any treatment in 14.9% vs 5.3%. Based on the observed efficacy and safety, the external data monitoring committee recommended that the study be stopped due to futility and that participants discontinue ipi/placebo. Conclusion
Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab alone as first-line therapy for metastatic NSCLC with PD-L1 TPS ≥50% and no targetable EGFR or ALK aberrations. These data confirm pembrolizumab monotherapy as a standard-of-care for this population.
