158P Durvalumab (D) ± tremelimumab (T) + chemotherapy (CT) in first-line metastatic NSCLC (mNSCLC): Pharmacokinetics (PK) and anti-drug antibody (ADA) data from the phase III POSEIDON trial

PURPOSE Pembrolizumab monotherapy is standard first-line therapy for metastatic non–small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. METHODS In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234 ), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. RESULTS Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P = .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; P = .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo. CONCLUSION Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population.

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Phase III, randomized, open-label study of durvalumab (MEDI4736) in combination with tremelimumab or durvalumab alone versus platinum-based chemotherapy in first-line treatment of patients with advanced/metastatic NSCLC: MYSTIC

Journal for ImmunoTherapy of Cancer ◽

10.1186/2051-1426-3-s2-p171 ◽

2015 ◽

Vol 3 (S2) ◽

Cited By ~ 5

Author(s):

Naiyer Rizvi ◽

Fabrice Barlesi ◽

Julie Brahmer ◽

Enriqueta Felip ◽

Patrick Forde ◽

...

Keyword(s):

Phase Iii ◽

Line Treatment ◽

First Line ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Metastatic Nsclc ◽

Platinum Based Chemotherapy ◽

First Line Treatment

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120O Pembrolizumab (Pembro) with or without lenvatinib (Lenva) in first-line metastatic NSCLC with PD-L1 TPS ≥1% (LEAP-007): A phase III, randomized, double-blind study

Annals of Oncology ◽

10.1016/j.annonc.2021.10.139 ◽

2021 ◽

Vol 32 ◽

pp. S1429-S1430

Author(s):

J.C-H. Yang ◽

A. Luft ◽

E. De La Mora Jiménez ◽

J.S. Lee ◽

P. Koralewski ◽

...

Keyword(s):

Blind Study ◽

Phase Iii ◽

Double Blind Study ◽

First Line ◽

Double Blind ◽

Metastatic Nsclc

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B-F1RST: Assessment of novel blood-based biomarkers in patients with first-line advanced or metastatic NSCLC receiving atezolizumab monotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.tps9103 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. TPS9103-TPS9103

Author(s):

Edward S. Kim ◽

Mark A. Socinski ◽

Shaker R. Dakhil ◽

Niklas J. Mackler ◽

Nadeem Ikhlaque ◽

...

Keyword(s):

Clinical Trial ◽

Locally Advanced ◽

Predictive Biomarkers ◽

The United States ◽

Phase Iii ◽

First Line ◽

Open Label ◽

Eligibility Criteria ◽

Metastatic Nsclc ◽

Cell Immunity

TPS9103 Background: The anti–PD-L1 monoclonal antibody atezolizumab inhibits the interaction of PD-L1 with its receptors PD-1 and B7.1, thereby restoring T-cell immunity. In the Phase III OAK study, patients with previously treated advanced NSCLC had improved mOS in the atezolizumab arm (13.8 mo) vs the docetaxel arm (9.6 mo) (HR 0.73 [95%CI: 0.62, 0.87]; P= 0.0003), irrespective of PD-L1 expression or histology. A Phase III clinical trial of atezolizumab monotherapy for first-line, PD-L1–selected patients with NSCLC is underway; however, first-line atezolizumab monotherapy for NSCLC treatment in a biomarker-unselected population has not yet been investigated. Current assays to measure PD-L1 expression by IHC require tumor biopsies, which can be difficult to obtain in some patients. Novel blood-based biomarkers will be evaluated retrospectively in B-F1RST (Blood-First-Line Ready Screening Trial) in patients receiving atezolizumab monotherapy in first-line NSCLC. Methods: A Phase II, open-label, single-arm study, B-F1RST (NCT02848651), will evaluate the efficacy and safety of atezolizumab in PD-L1–unselected patients with first-line locally advanced or metastatic NSCLC. Eligibility criteria include stage IIIB-IVB NSCLC, ECOG PS 0-1, measurable disease per RECIST v1.1 and adequate hematologic and end-organ function. Exclusion criteria include the presence of EGFRmutations or ALKfusions, active CNS metastases and prior immunotherapy for NSCLC. Patients will receive atezolizumab 1200 mg IV q3w until disease progression or loss of clinical benefit. Prospective collection of blood samples is mandatory; collection of tissue biopsies is optional. The co-primary endpoints of the study are investigator-assessed ORR per RECIST v1.1 for the efficacy objective and PFS per RECIST v1.1 for evaluating blood-based predictive biomarkers for atezolizumab efficacy, including mutation status. Approximately 150 patients will be enrolled at 25 or more centers in the United States. Clinical trial information: NCT02848651.

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