Conference Calendar - ESMO Immuno-Oncology 2021 Onsite and Online Congress

Mini Oral session Mini Oral session

122MO - Nivolumab (NIVO) + ipilimumab (IPI) as first-line (1L) treatment (tx) for patients (pts) with advanced NSCLC (aNSCLC) and baseline (BL) brain metastases (mets): intracranial and systemic outcomes from Checkmate 227 Part 1

Presentation Number

122MO

Lecture Time

11:45 - 11:50

Speakers

Martin Reck (Grosshansdorf, Germany)

Session Name

Mini Oral session

Room

Room C

Date

Thu, 09.12.2021

Time

11:00 - 12:40

Abstract

Abstract

Background

First-line NIVO + IPI has been shown to improve survival and systemic efficacy vs chemo in pts with aNSCLC with and without BL brain mets in a post hoc analysis from CheckMate 227 Part 1 (NCT02477826). Here we report intracranial and systemic efficacy, and safety data with a 4-y minimum follow-up.

Methods

Pts with untreated stage IV/recurrent NSCLC, no EGFR/ALK alterations, and ECOG PS 0–1 (stratified by histology) were randomized to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 240 mg Q2W, or chemo (PD-L1 ≥ 1%); or NIVO + IPI, NIVO 360 mg Q3W + chemo, or chemo (PD-L1 < 1%). Pts with treated brain mets who were asymptomatic for ≥ 2 wks prior to randomization were eligible; corticosteroids were permitted as described previously (AACR 2020 #CT221). Brain MRI/CT was performed in all pts at BL, and in pts with BL brain mets every ∼12 wks thereafter until disease progression. Radiographic assessment of intracranial tumor response was per mRECIST v1.1 by blinded independent central review (BICR).

Results

BL characteristics were generally similar between pts with (n = 134) and without (n = 1032) BL brain mets, and between tx arms, except for a greater proportion of pts with squamous histology and ECOG PS 0 in the no BL brain mets subgroup (both tx arms) and fewer pts with liver mets in the BL brain mets subgroup (NIVO + IPI). Efficacy data are shown in the table. NIVO + IPI prolonged OS vs chemo in pts with BL brain mets (HR 0.63, 95% CI 0.43–0.92). Median intracranial PFS was 8.6 vs 8.7 mo (HR 0.80, 95% CI 0.5–1.27); 4-y intracranial PFS rates were 28% vs 7%. In pts with BL brain mets, any-grade neurologic treatment-related adverse events occurred in 16% (NIVO + IPI) and 17% (chemo) of pts; all were grade 1/2.Table: 122MO

Table. Efficacy by BL brain mets in CheckMate 227
	With BL brain mets				Without BL brain mets
	Systemic		Intracranial		Systemic
	NIVO+IPI n = 68	Chemo n = 66	NIVO+IPI n = 68	Chemo n = 66	NIVO+IPI n = 515	Chemo n = 517
Median OS, mo 95% CI	17.4 9.2–28.5	13.7 10.5–16.2	–	–	17.1 15.3–20.0	13.9 11.8–15.3
HR vs chemo 95% CI	0.63 0.43–0.92		–		0.75 0.65–0.86
4-y OS rate, %	28	8	–	–	27	16
Median PFS,^amo 95% CI	5.4 3.0–8.6	5.8 4.3–8.0	8.6 5.7–19.5	8.7 6.6–11.5	4.9 4.1–5.8	5.4 4.5–5.6
HR vs chemo 95% CI	0.77 0.52–1.16		0.80 0.50–1.27		0.80 0.69–0.92
4-y PFS rate, %	15	2	28	7	13	3
ORR,^a n (%)	22 (32)	17 (26)	20 (29)	19 (29)	173 (34)	145 (28)
Median DOR,^a mo	24.9	8.4	45.5	32.0	20.7	5.8
^aPer BICR.

Conclusions

At 4-y minimum follow-up, 1L NIVO + IPI showed durable survival benefit and a trend towards improved intracranial efficacy vs chemo in pts with aNSCLC and BL brain mets; no new safety signals were observed.

Clinical trial identification

NCT02477826.

Editorial acknowledgement

All authors contributed to and approved the presentation; writing and editorial assistance were provided by Ashvanti Valji, PhD, of Caudex, London, United Kingdom, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb (Princeton, NJ).

Funding

Bristol Myers Squibb.

Disclosure

M. Reck: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche, Samsung; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Boehringer Ingelheim; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche. T. Ciuleanu: Financial Interests, Personal, Advisory Role: AstraZeneca, Amgen, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Janssen, MSD, Novartis/GSK, Roche, Sanofi, Servier, Pfizer; Non-Financial Interests, Personal, Other, Travel / Accommodations / Expenses: AstraZeneca, Amgen, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Janssen, MSD, Novartis/GSK, Roche, Sanofi, Servier, Pfizer. A. Pluzanski: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel / Accommodations / Expenses: Bristol Myers Squibb. R. Bernabe Caro: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, MSD, Takeda, Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Research Grant: Roche. H. Linardou: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. J. Burgers: Financial Interests, Personal and Institutional, Research Grant: MSD; Non-Financial Interests, Personal and Institutional, Advisory Board: Roche; Non-Financial Interests, Personal and Institutional, Funding: Roche. C. Gallardo: Financial Interests, Personal, Other, Consulting: MSD, AstraZeneca; Financial Interests, Personal, Other, Honoraria: MSD, AstraZeneca, Novartis, Roche; Financial Interests, Personal, Expert Testimony: AstraZeneca, Novartis; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Roche, MSD. M. Nishio: Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Research Grant: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Advisory Board: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Advisory Board: Merck Biopharma; Financial Interests, Personal, Speaker’s Bureau: Merck Biopharma; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Research Grant: Takeda; Financial Interests, Personal, Advisory Board: Teijin Pharma; Financial Interests, Personal, Speaker’s Bureau: Teijin Pharma; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Speaker’s Bureau: AbbVie. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody; Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda; Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. L. Paz-Ares: Financial Interests, Personal, Leadership Role: Genomica, ALTUM sequencing; Non-Financial Interests, Personal, Speaker’s Bureau: MSD Oncology, Bristol Myers Squibb, Roche / Genentech, Pfizer, Lilly, Merck Serono; Financial Interests, Personal, Other, Travel / Accommodations / Expenses: Roche, AstraZeneca, MSD, Bristol Myers Squibb, Pfizer, Takeda; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Bristol Myers Squibb, Roche / Genentech, Pfizer, Lilly, Merck Serono, AstraZeneca, Pharma Mar, Novartis, Celgene, Amgen, Sanofi, Ipsen, Servier, Bayer, Blueprint Medicines, Mirati Therapeutics, Takeda; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, AstraZeneca, Pharma Mar, Kura Oncology, MSD. M. Hellmann: Financial Interests, Personal, Advisory Role: Merck, Bristol Myers Squibb, AstraZeneca, Genentech, Roche, Natera, Mirati, Shattuck Labs, Immunai, Blueprint Medicines, Achilles, Arcus, Adagene, Adicet, DaVolaterra, Eli Lilly, Genzyme/Sanofi, Janssen, Regeneron, Instil Bio, Mana Therapeutics, Pact Phar; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Shattuck Labs, Immunai, Arcus, Factorial; Financial Interests, Institutional, Licensing Fees, patent filed by MSKCC (PCT/US2015/062208) which has received licensing fees from PGDx: MSKCC. H. Borghaei: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Lilly, Celgene, Genentech, Pfizer, Boehringer Ingelheim, EMD Serono, Trovagene, Novartis, Merck, AstraZeneca, Genmab, Regeneron, Cantargia AB, BioNTech AG, AbbVie, Pharma Mar, Takeda, Amgen, HUYA Bioscience International, Sonnet, Rge; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Lilly, Celgene, Pfizer, Merck, Axiom Biotechnologies; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Lilly, Celgene, Merck, Millenium; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Bristol Myers Squibb, Lilly, Celgene, Genentech, Novartis, Merck, Clovis Oncology; Financial Interests, Personal, Stocks/Shares: Sonnet, Rgenix, Nuclaei; Financial Interests, Personal, Other, Data Safety Monitoring Board: Takeda, University of Pennsylvania, Incyte. S.S. Ramalingam: Financial Interests, Personal, Advisory Role: Amgen, Genentech/Roche, Lilly, Bristol Myers Squibb, AstraZeneca, Merck, Takeda, GlaxoSmithKline, Eisai, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Research Grant: EMD Serono, Genmab, Advaxis, Tesaro, Bristol Myers Squibb, AstraZeneca, Merck, Takeda, GlaxoSmithKline. K. O’Byrne: Financial Interests, Personal, Advisory Role: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Lilly Oncology, Novartis, Janssen, Teva, Takeda, Yuhan, Natera, Tristar; Financial Interests, Personal, Other, Honoraria: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Lilly Oncology, Novartis, Janssen, Teva, Takeda, Yuhan, Natera, Tristar; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Lilly Oncology, Novartis, Janssen, Teva; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Lilly Oncology, Janssen; Non-Financial Interests, Personal, Speaker’s Bureau: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: RepLuca Pharmaceuticals, Carpe Vitae Pharmaceuticals, DGC Diagnostics; Non-Financial Interests, Personal, Member of the Board of Directors: Carpe Vitae Pharmaceuticals. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. L. Eccles: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Grootendorst: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J.R. Brahmer: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bristol Myers Squibb, Genentech, Merck, GlaxoSmithKline, Sanofi; Financial Interests, Personal, Other, Consulting: Amgen, AstraZeneca, Bristol Myers Squibb, Genentech, Merck, GlaxoSmithKline, Sanofi, Regeneron; Financial Interests, Personal, Other, Honoraria: Genentech; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Genentech; Financial Interests, Personal, Other, Data & Safety Monitoring Board Committee: GlaxoSmithKline, Sanofi. All other authors have declared no conflicts of interest.

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