Displaying One Session

Barcelona Auditorium (Hall 2) Proffered Paper session
Date
30.09.2019
Time
10:15 - 11:45
Location
Barcelona Auditorium (Hall 2)
Chairs
  • Marleen Kok (Amsterdam, Netherlands)
  • Francois Ghiringhelli (Dijon, France)
Proffered Paper – Immunotherapy of cancer Proffered Paper session

1174O - Pembrolizumab in microsatellite instability high cancers: Updated analysis of the phase II KEYNOTE-164 and KEYNOTE-158 studies (ID 569)

Presentation Number
1174O
Lecture Time
10:15 - 10:30
Speakers
  • Luis A. Diaz (New York, United States of America)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
10:15 - 11:45

Abstract

Background

Pembrolizumab (pembro) is indicated for patients (pts) with microsatellite instability-high (MSI-H) solid tumors after 1 prior therapy, and MSI-H colorectal cancer (CRC) after prior fluoropyrimidine, oxaliplatin, and irinotecan, based in part on data showing durable clinical benefit with pembro in the phase II studies KEYNOTE (KN)164 ([NCT02460198] in 61 pts (cohort A) with MSI-H CRC) and KN158 ([NCT02628067] in19 pts with MSI-H non-CRC). Here, we report results of the antitumor activity of pembro in pts with MSI-H tumors from a pooled analysis of KN164 and KN158, with ≥18 mo of additional follow-up across 28 tumor types.

Methods

KN164 enrolled pts with MSI-H CRC (cohort A [≥2 prior], cohort B [≥1 prior therapy]), while KN158 included pts with MSI-H non-CRC (≥1 prior therapy). MSI-H status was determined locally by IHC or PCR or centrally by PCR. Eligible pts in both received pembro 200 mg Q3W. Tumor response was assessed every 9 wk. Primary endpoint was ORR by central review per RECIST v1.1. Data cutoff date was Sept 4, 2018 for KN164 and Dec 6, 2018 for KN158.

Results

At data cutoff, 357 pts (124 with MSI-H CRC, 233 with MSI-H non-CRC) were enrolled. Pts had median age of 59 years (range 20-87) and 350 (98%) had ≥1 prior therapy. Common MSI-H non-CRC tumor types included endometrial (n = 49), gastric (n = 24), cholangiocarcinoma (n = 22), pancreatic (n = 22), small intestinal (n = 19), ovarian (n = 15), brain (n = 13), sarcoma (n = 9), neuroendocrine (n = 7), cervical and prostate (n = 6) cancers. Median follow-up was 18.0 mo (range 0.1-35.6). Confirmed ORR was 34% (n = 121; 95% CI 29-39); 30 (8%) pts had CR. Median DOR was not reached (range 2.9 to 31.3+); 54% of pts had response duration ≥18 mo. Median OS was 27.8 months mo (95% CI 21.3 to not reached), with 2-year OS rate of 52%. Median PFS was 4.0 mo (95% CI 2.5-4.3) with 2-year PFS rate of 31%. Serious drug-related events occurred in 11 (9%) pts with MSI-H CRC and 18 (8%) pts with MSI-H non-CRC. The safety profile was consistent with that previously seen for pembro. A pooled safety analysis will be presented.

Conclusions

Pembro provides robust antitumor activity with durable responses and a manageable safety profile in pts with MSI-H cancers independent of tumor type.

Clinical trial identification

KN164 NCT02460198 KN158 NCT02628067.

Editorial acknowledgement

Luana Atherly-Henderson, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck & Co., Inc.

Disclosure

L.A. Diaz: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck & Co., Inc.; Advisory / Consultancy: Caris; Advisory / Consultancy: Lyndra; Advisory / Consultancy: Genocea Biociences; Advisory / Consultancy: Illumina; Advisory / Consultancy: Cell Design Labs; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Neophore; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: PGDx; Officer / Board of Directors: Jounce Therapeutics; Licensing / Royalties: Johns Hopkins; Licensing / Royalties: MSKCC; Spouse / Financial dependant: Amgen. D. Le: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck & Co., Inc.; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Aduro Biotech. M. Maio: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: GSK; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: MedImmune. P.A. Ascierto: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution): Array; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Pierre Fabre, Incyte; Advisory / Consultancy: Genmab; Advisory / Consultancy: Newlink Genetics; Advisory / Consultancy: MedImmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Syndax; Advisory / Consultancy: Sun Pharma; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Idera; Advisory / Consultancy: Ultimovacs; Advisory / Consultancy: Sandoz; Advisory / Consultancy: Immunocore; Advisory / Consultancy: 4SC. R. Geva: Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy, Educational grant to the research unit - Novartis: Novartis; Honoraria (institution), Travel / Accommodation / Expenses: BMS; Honoraria (institution): Lilly; Honoraria (institution): Medison; Honoraria (institution), Travel / Accommodation / Expenses: Roche; Honoraria (institution): Janssen; Honoraria (institution): Takeda; Honoraria (institution), Travel / Accommodation / Expenses: Merck & Co., Inc. D. Motola-Kuba: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Asopharma; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: MSD. T. André: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: HalioDx; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Servier. E. Van Cutsem: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Ipsen. J. Delord: Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Novartis. D. Jäger: Advisory / Consultancy: Roche; Advisory / Consultancy: BMS; Advisory / Consultancy: Bayer. T.W. Kim: Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer. R. Guimbaud: Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: MSD; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Merck & Co., Inc.; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Novartis. T. Yoshino: Research grant / Funding (institution): Novartis K.K.; Research grant / Funding (institution): MSD K.K.; Research grant / Funding (institution): Sumitomo Dainippon Pharma ; Research grant / Funding (institution): Chungai Pharmaceutical; Research grant / Funding (institution): Sanofi K.K.; Research grant / Funding (institution): Daiichi Sankyo Company; Research grant / Funding (institution): PAREXEL International Inc; Research grant / Funding (institution): Ono Pharmaceutical Co. M. Chen: Full / Part-time employment: Merck & Co., Inc. K. Norwood: Full / Part-time employment: Merck & Co., Inc. P. Marinello: Full / Part-time employment: Merck & Co., Inc. A. Marabelle: Advisory / Consultancy: Merck Serono; Advisory / Consultancy: eTheRNA; Advisory / Consultancy: Lytix pharma; Advisory / Consultancy: Kyowa Kirin Pharma; Honoraria (institution), Advisory / Consultancy: Bayer; Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: BMS; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Genmab; Advisory / Consultancy: Amgen; Advisory / Consultancy: Biothera; Advisory / Consultancy: Nektar; Advisory / Consultancy: GSK; Advisory / Consultancy: Oncovir; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Flexus Bio; Advisory / Consultancy: Roche/Genentech; Honoraria (institution), Speaker Bureau / Expert testimony: Roche; Honoraria (institution): Pierre Fabre; Honoraria (institution): Onxeo; Honoraria (institution): EISAI; Honoraria (institution): Genticel; Honoraria (institution): Rigontec; Honoraria (institution): Daiichi Sankyo; Honoraria (institution): Imaxio; Honoraria (institution): Sanofi; Honoraria (institution): BioNTech. All other authors have declared no conflicts of interest.

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Proffered Paper – Immunotherapy of cancer Proffered Paper session

1192O - Association of tumour mutational burden with outcomes in patients with select advanced solid tumours treated with pembrolizumab in KEYNOTE-158 (ID 4445)

Presentation Number
1192O
Lecture Time
10:30 - 10:45
Speakers
  • Aurélien Marabelle (Villejuif, France)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
10:15 - 11:45

Abstract

Background

Tumor mutational burden (TMB) has been correlated with response to CTLA-4 and PD-(L)1 inhibitors. We explored the association of TMB with outcomes in cohorts A through J of KEYNOTE-158, a phase II basket study of pembrolizumab monotherapy for patients (pts) with select advanced solid tumors (NCT02628067).

Methods

Key eligibility criteria were progression on or intolerance to ≥ 1 line of standard therapy, ECOG PS 0 or 1, provision of a tumor sample for biomarker analysis, and either anal, biliary, cervical, endometrial, salivary, thyroid, or vulvar carcinoma, mesothelioma, a neuroendocrine tumor, or SCLC. Pts received pembrolizumab 200 mg Q3W for 35 cycles or until PD, intolerable toxicity, or physician or pt decision. TMB was assessed in FFPE tumor samples using the FoundationOne CDx™ assay. TMB-high was defined as 10 Mut/Mb. Primary study endpoint was ORR (RECIST v1.1, central review); DOR, PFS, OS, and safety were secondary endpoints. The relationship between antitumor activity and TMB was an exploratory endpoint.

Results

Of the 1032 pts with ≥26 weeks of follow-up as of 06 Dec 2018, 755 (73.2%) had evaluable TMB; of these, 120 (15.9%) were TMB-high, with 15/120 (12.5%) known to be MSI-H. Baseline characteristics were generally similar for TMB-high and low. There was low correlation between TMB and PD-L1 expression (ρ = 0.19). ORR (95% CI) was 28.3% (20.5-37.3) for TMB-high (24.8% [16.9-34.1] non–MSI-H) and 6.5% (4.7-8.7) for TMB-low. Median DOR was not reached for TMB-high or low (range 2.2+ to 28.8+ and 4.1 to 30.6+, respectively). Median (95% CI) PFS for TMB-high and low was 2.1 mo (2.1-3.7) and 2.1 mo (2.1-2.3), respectively; 12-mo rates were 24.3% and 14.0%. Median (95% CI) OS for TMB-high and low was 11.1 mo (8.1-16.1) and 13.3 mo (11.5-14.8), respectively; 12-mo rates were 48.0% and 52.9%. The safety profile was consistent with that previously observed for pembrolizumab.

Conclusions

TMB-high was associated with higher ORR in pts with select advanced solid tumors treated with pembrolizumab monotherapy. The tail of the PFS curve favored TMB-high. These data suggest that TMB may be predictive of the efficacy of pembrolizumab monotherapy in pts with the tumor types included in KEYNOTE-158.

Clinical trial identification

NCT02628067, December 11, 2015.

Editorial acknowledgement

Melanie Leiby of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

A. Marabelle: Research grant / Funding (institution), principal investigator: Roche/Genentech, BMS, Merck (MSD), Pfizer, Lytix pharma, Eisai, AstraZeneca/MedImmune, Tesaro, Chugai ; Research grant / Funding (institution): MSD; Travel / Accommodation / Expenses: MSD, AstraZeneca, Roche/Genentech, BMS ; Research grant / Funding (institution), rincipal investigator, sponsor Unicancer; ACSE NIVOLUMAB/NCT03012581 : INCa, Ligue contre le Cancer & BMS; Research grant / Funding (institution), principal investigator, sponsor Leon Berard Cancer Center; ISIJX/NCT02977156: Transgene; Research grant / Funding (institution), principal investigator, sponsor Gustave Roussy; NIVIPIT/NCT02857569 : BMS; Research grant / Funding (institution), principal investigator, sponsor Gustave Roussy; PEMBIB/NCT02856425 : Boehringer Ingelheim; Research grant / Funding (institution): Astrazeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi ; Non-remunerated activity/ies, drug supply: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche ; Advisory / Consultancy: GSK, AstraZeneca; Advisory / Consultancy: Oncovir, Inc.; Advisory / Consultancy: Innate Pharma, Merck Serono, eTheRNA, Lytix pharma, Kyowa Kirin Pharma, Bayer, Novartis, BMS, Symphogen, Genmab, Amgen, Biothera, Nektar, GSK, Oncovir, Pfizer, Seattle Genetics, Flexus Bio, Roche/Genentech, OSE immunotherapeutics, Transgene, Gritstone, ; Speaker Bureau / Expert testimony: Roche/Genentech, BMS, Merck (MSD), Merck Serono, AstraZeneca/MedImmune, Amgen, Sanofi ; Advisory / Consultancy: Roche, Pierre Fabre, Onxeo, EISAI, Bayer, Genticel, Rigontec, Daiichi Sankyo, Imaxio, Sanofi, BioNTech, Corvus, GLG, Deerfield, Guidepoint Global, Edimark, System Analytics, imCheck, Sotio, Bioncotech, Molecular Partners, Pillar Partners, Boehringer Inge; Shareholder / Stockholder / Stock options: Pegascy SAS (Gustave Roussy Spin Off for Drug Repositioning) ; Research grant / Funding (institution): Merus, BMS, Boehringer Ingelheim, Transgene, Fondation MSD Avenir; Officer / Board of Directors, supervisory board member: Gustave Roussy Foundation; Advisory / Consultancy, steering committee of the immuno-oncology task force: Unicancer; Research grant / Funding (institution), sub-investigator of clinical trials: Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boehringer Ingelheim, Bristol; Licensing / Royalties, Patent Issued (not licensed yet) : “Humanized and Chimeric Monoclonal Antibodies to CD81”, Stanford Office of Technology Licensing, 3000 El Camino Real, Bldg. 5, Suite 300, Palo Alto, CA 94306-2100. U.S. Application Serial No. 62/351,054. M.G. Fakih: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Amgen; Advisory / Consultancy: Array; Advisory / Consultancy: Bayer; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Novartis; Research grant / Funding (institution): MSD. J. Lopez: Advisory / Consultancy: Genmab; Advisory / Consultancy: Novartis; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Basilea. M. Shah: Research grant / Funding (institution): MSD. R. Shapira-Frommer: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self): BMS; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Medison; Advisory / Consultancy: Clovis Oncology. K. Nakagawa: Research grant / Funding (institution): MSD. H.C. Chung: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self): Foundation Medicine; Advisory / Consultancy, Research grant / Funding (institution): Taiho; Advisory / Consultancy: Celltrion; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Quintiles; Advisory / Consultancy: BMS; Research grant / Funding (institution): GSK; Research grant / Funding (institution): BMS-ONO. H.L. Kindler: Research grant / Funding (institution): MSD. J.A. Lopez-Martin: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Celgene; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: PharmaMar; Advisory / Consultancy: Chobani. W. Miller: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): GSK; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Methylene; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Astellas. A. Italiano: Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Epizyme; Advisory / Consultancy: ImmuneDesign; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): PharmaMar. S. Kao: Research grant / Funding (institution): MSD. S.A. Piha-Paul: Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Aminex Therapeutics; Research grant / Funding (institution): BioMarin Pharmaceutical, Inc; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Cerulean Pharma Inc.; Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd; Research grant / Funding (institution): Curis; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Flex Bio, Inc; Research grant / Funding (institution): Genmab A/S; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Helix BioPharma Corp; Research grant / Funding (institution): Incyte Corp; Research grant / Funding (institution): Jacobio Pharmaceuticals Co., Ltd; Research grant / Funding (institution): MedImmune, LLC; Research grant / Funding (institution): Medivation, Inc.; Research grant / Funding (institution): Merck Sharp and Dohme Corp; Research grant / Funding (institution): NewLink Genetics Corporation/Blue Link Pharmaceuticals; Research grant / Funding (institution): Novartis Pharmaceuticals; Pieris Pharmaceuticals, Inc.; Pfizer; Principia Biopharma, Inc.; Puma Biotechnology, Inc.; Seattle Genetics; Taiho Oncology; Tesaro, Inc.; TransThera Bio; XuanZhu Biopharma. J. Delord: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Research grant / Funding (institution): MSD; Advisory / Consultancy: EMD Serono; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): AstraZeneca. R.R. McWilliams: Advisory / Consultancy: Ipsen; Advisory / Consultancy: NewLink Genetics; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): MSD. D. Aurora-Garg: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck Sharp & Dohme Corp. M. Chen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck Sharp & Dohme Corp. F. Jin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck Sharp & Dohme Corp. K. Norwood: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck Sharp & Dohme Corp. Y. Bang: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck Serano; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Taiho; Advisory / Consultancy, Research grant / Funding (institution): Daiichi-Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy, Research grant / Funding (institution): GreenCross; Advisory / Consultancy: Biopharm; Advisory / Consultancy: Hanmi; Advisory / Consultancy, Research grant / Funding (institution): Genexine; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): MacroGenics, Boston Biomedical, FivePrime, Curis, Takeda, Ono, CKD Pharma.

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Proffered Paper – Immunotherapy of cancer Proffered Paper session

Invited Discussant 1174O and 1192O (ID 7293)

Lecture Time
10:45 - 11:00
Speakers
  • Francois Ghiringhelli (Dijon, France)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
10:15 - 11:45
Proffered Paper – Immunotherapy of cancer Proffered Paper session

1175O - Durvalumab activity in previously treated patients who stopped durvalumab without disease progression (ID 2365)

Presentation Number
1175O
Lecture Time
11:00 - 11:15
Speakers
  • Siddharth Sheth (Chapel Hill, United States of America)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
10:15 - 11:45

Abstract

Background

A proportion of cancer patients treated with anti-programmed cell death-1 (PD-1) and its ligand (PD-L1) achieve long-lasting responses. Some of these patients stop treatment without disease progression (DP). Limited data exist on re-initiation of the same PD-1/PD-L1 inhibitor upon progression.

Methods

In NCT01693562, a phase I/II study evaluating durvalumab in advanced solid tumors, patients were treated until DP or up to 1 year. Per protocol, patients who benefited from durvalumab and stopped treatment after 1 year of therapy were eligible to be rechallenged at time of DP. Clinical outcomes analyzed were best overall response, duration of response, disease control rate (DCR), and progression-free survival (PFS), defined as time from first day of retreatment with durvalumab to DP or death.

Results

Of 1,022 patients, 160 stopped durvalumab without developing DP after 1 year of treatment. Of those, 70 (43.8%) patients across 14 different primary tumor types were rechallenged with durvalumab after DP (Table). During their first treatment with durvalumab, 5.7% and 50% had achieved complete responses (CR) and partial responses (PR), respectively. While off therapy, median time without DP was 266 days. After rechallenge with durvalumab, 66 of 70 (94.3%) were evaluable. Confirmed best overall response was 0% CR, and 11.4% had PR, 60% had stable disease (SD), and 22.9% had DP. Median duration of response was 16.5 months. DCR at ≥ 24 weeks was 47.1%. PFS at 12 months was 34.2%, with similar rates observed regardless of tumor type.

1175O Best overall response and 12-month PFS with durvalumab rechallenge

Tumour TypeAll Patients (N = 70)NSCLC (n = 21)MSI-High (n = 12)Bladder (n = 8)HNSCC (n = 6)HCC (n = 5)Other (n = 18)
Best overall response, n (%)
CR0000000
PR8 (11.4)3 (14.3)03 (37.5)01 (20.0)1 (5.6)
SD42 (60)8 (38.1)11 (91.7)3 (37.5)4 (66.7)4 (80.0)1212 (66.7)
DP16 (22.9)8 (38.1)1 (8.3)2 (25.0)2 (33.3)03 (16.7)
Nonevaluable4 (5.7)2 (9.5)00002 (11.1)
Duration of response, months16.513.4N/A16.5N/A18.7+12+
CR/PR + SD (DCR ≥24 weeks), %47.133.358.350.033.340.040.0
PFS at 12 months, %34.23159.462.5202572.2

Conclusions

This is the largest cohort supporting the role of rechallenge with a PD-1/PD-L1 inhibitor in patients who have previously progressed after planned interruption. Rechallenge with durvalumab resulted in restored antitumor efficacy, high rates of disease control, and prolonged durability in patients who responded. These findings support the role of durvalumab in patients who progressed after planned treatment interruption.

Clinical trial identification

NCT01693562.

Legal entity responsible for the study

AstraZeneca, PLC.

Funding

AstraZeneca.

Disclosure

S. Sheth: Research grant / Funding (institution): AstraZeneca. C. Gao: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. N. Mueller: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Martinez: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Soria: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca.

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Proffered Paper – Immunotherapy of cancer Proffered Paper session

1191O - Phase II study of olaparib (O) and durvalumab (D) (MEDIOLA): Updated results in patients (pts) with germline BRCA-mutated (gBRCAm) metastatic breast cancer (MBC) (ID 4019)

Presentation Number
1191O
Lecture Time
11:15 - 11:30
Speakers
  • Susan Domchek (Philadelphia, United States of America)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
10:15 - 11:45

Abstract

Background

O (olaparib, Lynparza®) is approved for gBRCAm HER2(-) MBC based on the OlympiAD study. O-induced DNA damage may increase tumor antigen release, activate cGAS/STING, attract tumor-infiltrating lymphocytes and upregulate programmed cell death ligand-1 (PD-L1). In OlympiAD (single-agent olaparib), median duration of response (DoR) and median progression-free survival (PFS) were 6.4 months (m) and 7.0 m, respectively. MEDIOLA assessed the efficacy and safety of the combination of O and D (durvalumab, Imfinzi®), an anti-PD-L1 antibody, in gBRCAm HER2(-) MBC (NCT02734004). Early results were reported (SABCS 2017 PD6-11, 2018 PD5-04).

Methods

Pts with gBRCAm HER2(-) MBC were eligible; prior platinum was allowed; prior PARPi or anti-PD(L)1 was not. Pts received O 300 mg BID for a 4-wk run-in, then O 300 mg BID and D 1.5g IV q 4 wks until disease progression. Tumors were assessed at baseline, 4 wks, then every 8 wks. Dual primary endpoints were disease control rate (DCR) at 12 wks and safety. Secondary endpoints were 28-wk DCR, objective response rate (ORR), DoR, PFS, overall survival (OS), and biomarker analysis.

Results

34 pts were in the safety, and 30 pts in the efficacy analyses. The 12-wk DCR was 24/30 (80%), greater than the target of 75%. The 28-wk DCR was 15/30 (50%). Other efficacy endpoints are presented below. The most common adverse events ≥Grade 3: anemia (Gr 3, 4 pts), neutropenia (Gr 3, 3 pts), and pancreatitis (Gr 3, 1pt, Gr 4, 1 pt). Efficacy and safety results with longer follow-up will be presented. Efficacy results correlated to genomic data and intrinsic subtypes will also be presented.

1191O

EndpointOverall Cohort (n = 30)0 prior lines n = 9 (7/9 TNBC)1 prior line n = 11 (5/11 TNBC)2 prior lines n = 10 (5/10 TNBC)
mPFS (mo) (95% CI)8.2 (4.6, 11.8)9.9 (2.2, 13.8)11.7 (1.9, NC)6.5 (1.0, 8.2)
mOS (mo) (95% CI)20.5 (16.2, 23.9)21.3 (9.0, NC)22.7 (10.1, NC)16.9 (4.6, NC)
Responses19775
ORR (95% CI)63.3% (43.9-80.1)78% (40.0, 97.2)64% (30.8, 89.1)50% (18.7, 81.3)
mDoR (mo) (IQR)9.2 (5.5, 20.3)9.2 (4.0, 12.9)NC (10.9, NC)5.5 (5.4, 5.5)

IQR, interquartile range; NC, not calculable; TNBC, triple-negative breast cancer

Conclusions

The data suggest that pts with fewer prior lines of chemotherapy (0/1) had higher ORR, longer mDoR, mPFS and mOS than those with 2 prior lines. The chemo-free combination was well-tolerated, with safety consistent with the individual agent profiles. Confirmation of these results in early-line patients is warranted.

Clinical trial identification

NCT02734004.

Editorial acknowledgement

Writing assistance was provided by Martin Goulding, PhD, of Mudskipper Ltd and funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca and the authors.

Funding

AstraZeneca.

Disclosure

S. Domchek: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Clovis Oncology; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (self): PharmaMar. S. Postel-Vinay: Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: AstraZeneca; Research grant / Funding (self), Non-remunerated activity/ies: Boehringer Ingelheim; Research grant / Funding (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Research grant / Funding (institution): Janssen-Cilag; Advisory / Consultancy, Research grant / Funding (self), Non-remunerated activity/ies: Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self), Non-remunerated activity/ies: Pfizer; Research grant / Funding (self), Non-remunerated activity/ies: Roche; Research grant / Funding (self): Sanofi; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: Johnson & Johnson; Non-remunerated activity/ies: Lilly; Non-remunerated activity/ies: MedImmune; Non-remunerated activity/ies: NH TherAGuiX. S. Im: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche. J. Alexandre: Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): PharmaMar; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self): Ipsen; Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen. M.G. Krebs: Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy: Octimet; Advisory / Consultancy: Achilles; Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (self), Travel / Accommodation / Expenses: BerGenBio; Research grant / Funding (self): MSD. M. Lanasa: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H.K. Angell: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Z. Lai: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. C. Gresty: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. L.M. Opincar: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Herbolsheimer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. B. Kaufman: Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.

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Proffered Paper – Immunotherapy of cancer Proffered Paper session

Invited Discussant 1175O and 1191O (ID 6791)

Lecture Time
11:30 - 11:45
Speakers
  • Marleen Kok (Amsterdam, Netherlands)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
10:15 - 11:45