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S.N. Waqar
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Immunotherapies and targeted therapies in advanced NSCLC (ID 39)
- Event: ELCC 2017
- Type: Proffered Paper session
- Track:
- Presentations: 1
- Moderators:L. Paz-Ares, N. Reguart
- Coordinates: 5/06/2017, 14:45 - 16:15, Room B
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83O - A phase II study of durvalumab (MEDI4736) for previously treated patients with stage IV squamous NSCLC (SqNSCLC): Lung-MAP Sub-study SWOG S1400A (ID 279)
14:45 - 16:15 | Author(s): S.N. Waqar
- Abstract
- Presentation
Background:
Durvalumab (MEDI4736) is an engineered human IgG1 mAb targeting programmed cell death ligand-1 (PD-L1). Treatment with other anti-PD-1/PD-L1 antibodies has demonstrated meaningful clinical benefit in patients with advanced NSCLC.
Methods:
As part of the Lung Master Protocol S1400, a National Clinical Trials Network group "umbrella" trial for second-line SqNSCLC we conducted a phase II study of durvalumab in patients with Stage IV squamous NSCLC (ECOG PS 0-2; ≥1 prior systemic treatment regimens, including one platinum-based), EGFR/ALK wild-type. The primary endpoint was overall response rate (ORR) (RECIST v1.1); secondary endpoints included duration of response (DoR), ORR among PD-L1 positive patients, disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS) and safety (CTCAE v4.03). The initial protocol was a randomized phase II/III comparison of durvalumab to docetaxel, and was amended to be a single arm phase II trial of single agent durvalumab. PD-L1 positive tumors were defined by ≥ 25% of tumor cells with membrane staining.
Results:
Of the 68 eligible patients (median [range] age 66 [35-92] years, PS 0/1/2 26%/62%/12%), 11 were responders (16% ORR, 95% Confidence Interval [CI] 7%, 25%). DCR was 54% (CI 43%, 66%), median OS was 11.5 months (CI 10.1-12.4 mos), and median PFS was 2.9 mos (CI 2.0-4.1 mos). Of the 11 responders, median time to response and DoR were 3.6 mos (CI 2.8-4.2 mos) and 18.6 months (95% CI 4.4-NR mos), respectively. Of the 14 PDL1-positive patients, 2 were responders (14% ORR, 95% CI 0%, 33%), DCR was 57% (CI 31%, 83%), median OS and PFS were 10.7 mos (CI 9.2-10.7 mos) and 2.3 mos (CI 1.4-4.9 mos), respectively. Durvalumab showed a manageable safety and tolerability profile; most adverse events (AEs) were low grade and resolved with treatment delay and/or immunosuppressive interventions. Grade ≥3 treatment-related AEs occurred in 23(34%) of patients. Drug-related AEs led to discontinuation in 6 patients (9%, 95% CI 2%, 16%).
Conclusions:
Durvalumab demonstrated clinical benefit and durable responses in a previously treated metastatic NSCLC population with manageable toxicity profile. Results are comparable with other anti-PD-1/PD-L1 therapies in metastatic, relapsed NSCLC.
Clinical trial identification:
NCT02766335
Legal entity responsible for the study:
Southwest Oncology Group/NCTN
Funding:
Lung-MAP supported in part by NIH/NCI grants CA180888, CA180819, CA180820, CA180821, CA180868, and by Amgen, AstraZeneca, Bristol-Myers Squibb Company Genentech and Pfizer through the Foundation for the National Institutes of Health, in partnership with Friends of Cancer Research.
Disclosure:
V. Papadimitrakopoulou: Advisory Role for: Eli Lilly&Co, Genentech, Janssen Global Sevices, Bristol-Myers Squibb, ARIAD, Astra Zeneca Pharmaceuticals, Novartis, Merck Corporate-sponsored research: Novartis, Astra Zeneca, Genentech, Merck, Janssen, ACEA, Bristol-Myers Squibb. H. Borghaei: Advisory: Bristol-Myers Squibb, Lilly, Genentech, Celgene, Pfizer, EMD-Serono, Boerhinger-Ingelheim, Trovagene, AstraZeneca, Research Support: Millenium, Merck, Celgene. K. Kelly: Advisory: Synta, AstraZeneca, Lilly, Clovis Oncology, ARIAD, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, G1 Therapeutics. Research: Millenium, Novartis, EMD Serono, Lilly, Genentech, Abbvie, Gilead, Celgene, Five Prime Therapeutics, Transgene. All other authors have declared no conflicts of interest.
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Targeted therapies and management of brain metastasis (ID 40)
- Event: ELCC 2017
- Type: Proffered Paper session
- Track:
- Presentations: 1
- Moderators:D.P. Carbone, S. Ekman
- Coordinates: 5/06/2017, 16:45 - 18:15, Room A
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88O - CNS activity of ensartinib in ALK+ non-small cell lung cancer (NSCLC) patients (pts) (ID 461)
16:45 - 18:15 | Author(s): S.N. Waqar
- Abstract
- Presentation
Background:
Ensartinib (X-396) is a potent ALK small molecule TKI with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. In animal studies, CNS concentration of ensartinib in mice given at the therapeutic dose was 4 times higher than the IC50 for growth inhibition of ALK+ cells in vitro. Ensartinib was significantly more effective than crizotinib (C) at inhibiting the intracranial (IC) growth of the SH-SY5Y neuroblastoma model harboring the F1174L mutation. We subsequently evaluated the CNS activity of ensartinib in pts with ALK+ NSCLC.
Methods:
In this multicenter phase I/II study, pts with ALK+ NSCLC were enrolled and given ensartinib orally on a continuous 28-day schedule. 225 mg QD was selected for further evaluation. Pts enrolled with asymptomatic CNS metastases (with or without systemic disease) who were ALK TKI naïve or had received prior C or a 2nd generation ALK TKI were allowed to enroll. Overall and systemic response was assessed using RECIST 1.1. CNS response was assessed using modified RANO criteria. Pts with only CNS disease had to have at least 1 measurable target lesion ≥ 3 mm in diameter.
Results:
26 pts with ALK+ NSCLC and baseline CNS metastases were treated at ≥ 200 mg. Of the 26 pts, 13 pts had baseline target lesions, and 13 pts had only non-target lesions. CNS responses were observed in ALK TKI naïve pts and pts that received prior C or a 2[nd] generation ALK TKI. In the 13 pts with baseline target CNS lesions, IC response rate (RR) was 69%, including 1 CR, and 31% had SD, a 100% disease control rate. In the 13 pts with only non-target baseline lesions, 1 CR was achieved and 8 pts had SD. The IC RR in the 3 ALK TKI naïve pts with baseline target lesions was 100%, and 62% in 8 pts that received prior C only. Of 2 pts with baseline target lesions who received a prior 2[nd] generation ALK TKI, 1 had a PR and 1 SD. Median duration of IC response in the 10 pts who responded (9 with target lesions, 1 with non-target lesions only) is 5.8+ months, with the longest duration being 24 months.
Conclusions:
Our clinical findings support the preclinical results that the use of ensartinib may result in favorable therapeutic outcomes in pts with ALK+ NSCLC with CNS metastases. The ongoing phase III eXalt3 study will assess CNS RR and time to CNS progression in pts receiving 1st-line ensartinib vs C.
Clinical trial identification:
NCT02767804 and NCT01625234
Legal entity responsible for the study:
Xcovery Holding Company
Funding:
Xcovery Holding Company
Disclosure:
K. L. Reckamp: Xcovery Holding Company research funds to institution Ariad consultant and research funds to institution. H. A. Wakelee: Peregrin: Consultant/Independent contractor and honorarium recipient. Novartis: Grants/research support, consultant, honorarium recipient. ACEA: Consultant and honorarium recipient. Pfizer: Grants/research support, consultant, honorarium recipient. BMS: Grants/research support. Xcovery: Grants/research support. Celgene: Grants/research support. Roche/Genentech: Grants/research support. Medimmune: Grants/research support. Lilly: Grants/research support. S. Patel: Research funding from: Bristol-Myers Squibb, Eli Lilly, MedImmune, Pfizer, Roche/Genentech, Xcovery. Speaking fees from: Boehringer Ingelheim, Merck. G. Blumenschein: Grants/Research Support Recipient, Consultant- BMS, Bayer, Merck, Celgene Consultant- Clovis, AbbVie Grants/Research Support Recipient- Novartis, Xcovery, Astrazeneca. J. W. Neal: Consulting or Advisory role: Clovis Oncology, CARET/Physicians Resource Management, Nektar, Boehringer Ingelheim Research Funding- Genentech/Roche, Merck, ArQule, Novartis, Exelixis, Boehringer Ingelheim, Nektar. B. Gitlitz: Speakers Bureau for Lilly Speakers Bureau for Genentech. F. Tan: Manager- Xcovery Holding Company Chief Medical Officer- Betta Pharmaceuticals. K. Harrow: Xcovery Holding Company- Full-time Employee. L. Horn: Consulting for Xcovery Holding Company, BMS, BI, abbvie, Genentech, Merck. All other authors have declared no conflicts of interest.
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