Browsing Over 268 Presentations
58P - The unexpected challenges of immunotherapy (ID 467)
- A. C. Olsson-Brown (Liverpool, United Kingdom)
- A. C. Olsson-Brown (Liverpool, United Kingdom)
- T. J. Guinan (Wirral, United Kingdom)
- M. McKay (Wirral, United Kingdom)
- S. Chow (Wirral, United Kingdom)
- R. Lord (Wirral, United Kingdom)
- M. Pirmohamed (Liverpool, United Kingdom)
- J. J. Sacco (Wirral, United Kingdom)
Abstract
Background
As the indications and licencing of oncological checkpoint inhibitors (CPI) expands rapidly there are increasing challenges. The need for increased capacity and delivery, support and toxicity management for patients receiving immunotherapy (IO) has been steadily increasing. It is not the numbers alone that are causing a shift in patient management but also the novelty of immune related adverse events (irAEs), the complexity of their management and longditudinaity of treatment.
Methods
This study retrospectively reviewed the number of patients receiving IO and assessed the impact of IO on treatment delivery, acute and inpatient services at the Clatterbridge Cancer Centre (CCC), a UK tertiary cancer centre, between June 2016 and June 2018.
Results
A total of 624 patients received licenced CPIs at CCC over the 2 year period. Over the study period there was a 3.7 fold increase in new patients commencing on treatment in the initial and final 6 month period. Five tumour groups were represented. CCC administered 1408 individual treatments in 2016/2017 rising to 3140 in 2017/18. An on-treatment review service (OTR) commenced in June 2017. The OTR activity has increased from 87 individual encounters in July 2017 to 244 in June 2018. Within acute services the centralised telephone triage service saw in increase in IO related calls from 84 calls in Q3 2016/2017 to 316 Q4 2017/2018. This has translated into increased face-to-face patient review with triage attendances rising from 13 to 166. Furthermore IO related admissions have increased from 15 to 120, equating to an 8 fold increase, between the first and last 6 months of the reviewed period.
Conclusions
Immunotherapy has significantly altered the oncological treatment landscape in a very short timeframe. This has left cancer centres ill equipped for the vast impact IO has had in terms of delivery demands, support and acute services. Whilst acute management protocols are plentiful they are alone insufficient to manage the increasing impact of IO. These novel and expanding needs require specific and innovative approaches to allow effective managment. In response to this CCC has developed a comprehensive IO strategy adopting a systems approach and incorporating education development, multilevel management protocols, collaborative working and IO specific services.
Legal entity responsible for the study
Clatterbridge Cancer Center.
Funding
Has not received any funding.
Disclosure
A.C. Olsson-Brown: MRC Clinical Fellow at the University of Liverpool; Medical Research Council Fellowship in Clinical Pharmacology and Therapeutics, funded by the MRC(MR/N025989/1), Roche Pharma, Eli Lilly, UCB Pharma, Novartis, the Universities of Liverpool & Manchester. R. Lord: Recipient of travel bursary: AstraZeneca. M. Pirmohamed: Programme Director: Medical Research Council Fellowship in Clinical Pharmacology and Therapeutics, funded by the MRC(MR/N025989/1), Roche Pharma, Eli Lilly, UCB Pharma, Novartis, the Universities of Liverpool & Manchester. J.J. Sacco: Grants and personal fees: Bristol Myers Squibb; Personal fees: Immunocore; Grants: AstraZeneca; Other: MSD Merck. All other authors have declared no conflicts of interest.
93P - Anti-tumor effects of a small molecule C-C chemokine receptor 4 inhibitor in mouse tumor models (ID 266)
- C. Li (Mountain View, United States of America)
- C. Li (Mountain View, United States of America)
- J. J. Campbell (Mountain View, CA, United States of America)
- L. S. Ertl (Mountain View, CA, United States of America)
- Z. Miao (Mountain View, United States of America)
- V. Chhina (Mountain View, United States of America)
- A. Kumamoto (Mountain View, United States of America)
- S. Yau (Mountain View, CA, United States of America)
- T. Dang (Mountain View, CA, United States of America)
- P. Zhang (Mountain View, CA, United States of America)
- T. J. Schall (Mountain View, CA, United States of America)
- R. Singh (Mountain View, CA, United States of America)
Abstract
Background
Chemokines and their receptors influence many hallmark processes in cancer. C-C Chemokine receptor 4 (CCR4) and its ligands are highly expressed in many types of human tumors, and are often associated with poor prognosis. CCR4 antagonism has been demonstrated to reduce tumor growth in various mouse tumor models. Here we have assessed a small molecule inhibitior of CCR4 as a therapeutic agent to potentiate the effects of anti-CTLA-4 in the CT26 and KCM tumor models.
Methods
The subcutaneous CT26 colon cancer model and the orthotopic KCM pancreatic cancer model were used to assess the effects of CCX6239, a CCR4 inhibitor, in combination with anti-CTLA-4 antibody. Mice implanted with CT26 cells were randomized into study groups on day 7 based on the pre-treatment tumor sizes. KCM cells were implanted directly into the pancreas. Dosing of CCX6239 and anti-CTLA-4 began on day 7. CCX6239 was dosed orally twice daily at 30mg/kg, and anti-CTLA-4 was dosed intraperitoneally on days 7, 11, and 15 at 100μg/mouse.
Results
Combined treatment with anti-CTLA-4 and CCR4 inhibitor significantly decreased tumor size and increased the proportion of long-term survivors in the CT26 model. Mice with tumor regression exhibited a high proportion of CD8 T cells that recognized a CT26-specific neoantigen, and these mice were resistant to re-inoculation with CT26 cells (without further dosing of either drug), while another type of tumor grew well in the same mice. In the KCM model, anti-CTLA-4 alone provided substantial tumor growth inhibition, which was further enhanced by CCX6239. Interestingly, CCX6239 alone also significantly reduced tumor burden in this model.
Conclusions
A specific CCR4 inhibitor reduces tumor growth either alone or in combiniation with anti-CTLA-4 in two preclinical models, suggesting CCR4 is a potential new target for cancer treatment.
Legal entity responsible for the study
ChemoCentryx Inc.
Funding
ChemoCentryx Inc.
Disclosure
C. Li, J.J. Campbell, L.S. Ertl, Z. Miao, V. Chhina, A. Kumamoto, S. Yau, T. Dang, P. Zhang, T.J. Schall, R. Singh: Full time employee and stock holder of ChemoCentryx Inc.
Radiotherapy to boost the immune system (ID 21)
- D. De Ruysscher (Maastricht, Netherlands)
- D. De Ruysscher (Maastricht, Netherlands)
LBA6 - Durvalumab with or without tremelimumab vs platinum-based chemotherapy as first-line treatment for metastatic non-small cell lung cancer: MYSTIC (ID 496)
- N. A. Rizvi (New York, NY, United States of America)
- N. A. Rizvi (New York, NY, United States of America)
- B. Chul Cho (Seoul, Korea, Republic of)
- N. Reinmuth (Gauting, Germany)
- K. Lee (Cheongju, Korea, Republic of)
- M. Ahn (Seoul, Korea, Republic of)
- A. Luft (Saint Petersburg, Russian Federation)
- M. Van den Heuvel (Nijmegen, Netherlands)
- M. Cobo (Málaga, Spain)
- A. Smolin (Moscow, Russian Federation)
- D. Vicente (Sevilla, Spain)
- V. Moiseyenko (Saint-Petersburg, Russian Federation)
- S. J. Antonia (Tampa, FL, United States of America)
- S. Le Moulec (Paris, CEDEX 5, France)
- G. Robinet (Brest, Cedex 2, France)
- R. Natale (Los Angeles, CA, United States of America)
- K. Nakagawa (Osaka, Japan)
- L. Zhao (Gaithersburg, United States of America)
- P. K. Stockman (Macclesfield, United Kingdom)
- V. Chand (Gaithersburg, United States of America)
- S. Peters (Lausanne, Switzerland)
Abstract
Background
Durvalumab (D), a human IgG1 mAb against PD-1 and CD80, has shown clinical activity in patients (pts) with non-small cell lung cancer (NSCLC). Tremelimumab (T) is a human IgG2 mAb against CTLA-4. D+T has previously also shown durable responses in metastatic NSCLC (mNSCLC). MYSTIC (NCT02453282) was an open-label, Phase 3 trial of first-line treatment with D vs platinum-based doublet chemotherapy (CT) and D+T vs CT in mNSCLC.
Methods
Eligible pts had mNSCLC; were immunotherapy/chemotherapy-naïve; and had no EGFR sensitising mutation or ALK rearrangement. Tumour cell (TC) PD-L1 expression (≥25% vs <25%) and histology were stratification factors. Patients were randomised (1:1:1) to D (20 mg/kg i.v. q4w); D+T (D: 20 mg/kg i.v. q4w; T: 1 mg/kg i.v. q4w [up to 4 doses]); or CT (intended up to 6 cycles; pemetrexed maintenance permitted in eligible pts) until disease progression. Primary endpoints were overall survival (OS) for D vs CT and OS and progression free survival (PFS; blinded independent central review [RECIST v1.1]) for D+T vs CT in pts with PD-L1 TC expression ≥25%, defined by the VENTANA PD-L1 (SP263) assay. Data cutoffs were 4 Oct 2018 (OS and safety) and 1 Jun 2017 (PFS).
Results
1118 pts were randomised. Baseline characteristics were balanced. Efficacy findings are presented for the 488 pts with PD-L1 TC ≥25%. Median OS was 16.3 vs 12.9 months for D vs CT (HR 0.76 [97.54% CI, 0.564, 1.019]; p=0.036) and 11.9 vs 12.9 months for D+T vs CT (HR 0.85 [98.77% CI, 0.611, 1.173]; p=0.202). Median PFS was 3.9 vs 5.4 months for D+T vs CT (HR 1.05 [99.5% CI, 0.722, 1.534]; p=0.705). 39.5% pts in the CT arm received subsequent immunotherapy after treatment discontinuation vs 6.1% and 3.1% pts in the D and D+T arms. Incidence of Grade 3/4 treatment-related AEs was 14.6%, 22.1% and 33.8% with D, D+T and CT, respectively. Efficacy based on additional PD-L1 cutoffs will be presented.
Conclusions
In pts with mNSCLC, while statistical significance was not achieved for primary OS and PFS endpoints, first-line D demonstrated clinically meaningful improvement in OS vs CT (PD-L1 TC ≥25%). Safety data were consistent with the known safety profiles of D+/-T. Further analyses are ongoing.
Editorial acknowledgement
Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Rebecca Douglas, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.
Clinical trial identification
NCT02453282 (release date: May 25, 2015).
Legal entity responsible for the study
AstraZeneca plc.
Funding
AstraZeneca.
Disclosure
N.A. Rizvi: Advisory boards: Abbvie, AZ, BMS, EMD Serono, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Neogenomics, Oncomed, Gritstone, Bellicum; Equity: Oncomed, Gritstone, Bellicum, ARMO; Royalties: PGDX. B. Chul Cho: Research funding: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD Consultancy: Novartis, AZ, BI, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD; Stock: TheraCanVac, Inc. N. Reinmuth: Personal fees: AstraZeneca, Roche, Boehringer-Ingelheim, Takeda, MSD, BMS, Novartis, Pfizer, Merck. A. Smolin: Grants: AstraZeneca; Grants and personal fees: AstraZeneca, Roche, MSD, BMS; Personal fees: BIOCAD, Boehringer-Ingelheim. S.J. Antonia: Advisory board/contracted research: BMS, Novartis, Merck, CBMG, Boehringer-Ingelheim, AstraZeneca/MedImmune, Memgen, FLX Bio, Nektar, Venn. G. Robinet: Grants and personal fees: AstraZeneca; Grants and personal fees: MSD; Personal fees: Boehringer-Ingelheim. R. Natale: Spouse: Employee (Medical Science Liaison) of AZ (salary/compensation completely unrelated to the contracted research work performed at my institution that is the subject of the submitted abstract). K. Nakagawa: Research funding: GlaxoSmithKline K.K., AstraZeneca K.K., Kyowa Hakko Kirin, Pfizer Japan Inc., AbbVie Inc., Novartis Pharma K.K., Nippon Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly Japan K.K., MSD K.K., Quintiles Inc., Ono Pharmaceutical, BMS, EPS International, Chugai Pharmaceutical, ICON Japan K.K., Gritstone Oncology, Inc., Linical, Yakult Honsha, Parexel International Corp., Otsuka Pharmaceutical, Astellas Pharma Inc., AC Medical Inc., Taiho Pharmaceutical, Merck Serono, EPS Associates, Quintiles Inc., Japan Clinical Research Operations, Eisai, PPD-SNBL K.K., Takeda Pharmaceutical, Covance Inc., inVentiv Health Japan, A2 Healthcare Corp., EP-CRSU; Honoraria: Astellas Pharma Inc., AstraZeneca K.K., Novartis Pharma K.K., Pfizer Japan Inc., Chugai Pharmaceutical, Ono Pharmaceutical, Nippon Boehringer-Ingelheim, BMS, Kissei Pharmaceutical, Eli Lilly Japan K.K., MSD K.K., EPS Holdings Inc., Showa Yakuhin Kako, Clinical Trial, CareNet, Inc., Nikkei Business Publications, Inc., Nichi-Iko Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Ayumi Pharmaceutical Corporation, Kyowa Hakko Kirin, Sym Bio Pharmaceuticals, Medicus Shuppan Publishers, Reno Medical K.K., Yodosha, Nanzando; Consulting or advisory role: Astellas Pharma Inc., Eli Lilly Japan K.K., Ono Pharmaceutical, Takeda Pharmaceutical. L. Zhao: Full time employment: AstraZeneca. P.K. Stockman: Full-time employee, stock ownership: AstraZeneca. V. Chand: Full-time employment: AstraZeneca; stock ownership: BMS. S. Peters: Personal fees: Abbvie, Amgen, AZ, Bayer, Biocartis, BI, BMS, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda; Non-financial support: Amgen, AZ, BI, BMS, Clovis, F. Hoffmann-La Roche, Illumina, MSD, Merck Serono, Novartis, Pfizer. All other authors have declared no conflicts of interest.
Immune checkpoint inhibitors (ID 53)
- E. De Vries (Groningen, Netherlands)
- E. De Vries (Groningen, Netherlands)
Immunotherapy for HCC (ID 85)
- B. Sangro (Pamplona, Spain)
- B. Sangro (Pamplona, Spain)
How to combine with I-O drugs (ID 235)
- J. B. Haanen (Amsterdam, Netherlands)
- J. B. Haanen (Amsterdam, Netherlands)
19P - Signs of immunosenescence in patients diagnosed with non-small cell lung cancer (ID 269)
- T. Soria Comes (Valencia, Spain)
- T. Soria Comes (Valencia, Spain)
- V. Palomar-Abril (Valencia, Spain)
- M. Martin Ureste (Valencia, Spain)
- J. Marco Buades (Valencia, Spain)
- M. Fernandez Llavador (Valencia, Spain)
- J. Garcia Sanchez (Valencia, Spain)
- M. Cancela Gomez (Valencia, Spain)
- I. Maestu Maiques (Valencia, Spain)
Abstract
Background
Lately, there has been a great evolution of immunotherapy in non-small cell lung cancer (NSCLC) due to its relationship with inflammation. There is also a growing interest in the changes produced in immune system with age (immunosenescence). However, it is unclear if these differences also exist among elderly patients with cancer compared to adult patients with the same diagnosis and this is the aim of our study.
Methods
We retrospectively studied patients diagnosed of NSCLC during January-December 2017 at the time of diagnosis, excluding patients with chronic infections or autoimmune diseases. Included cases were divided into two groups depending on age. Lymphocyte count by flow cytometry was gathered at baseline and we studied if there were statistically significant differences in lymphocyte populations between young (<70) and elderly patients (≥70). The non-parametric Mann-Whitney test was used.
Results
81 patients were analysed; 32 in the young group and 49 in the elderly group. Regarding the innate immunity, the median value of NK lymphocytes showed to be higher in the cohort of patients ≥70 years (295 vs 191 cells/mm3; p = 0.0014). Oppositely, the median value of B-lymphocytes was lower in elderly patients (99 vs 128 cells/mm3; p = 0.0282). The Spearman coefficient for the correlation between age and B-lymphocyte count supports this data: ρ = 0.36 (moderate association). However, there was no difference between the median values of T-lymphocytes (p = 0.142). Interestingly, analysing T-lymphocyte subsets we found that median CD8 value was higher in the elderly group (464 vs 309.5 cells/mm3; p = 0.0226) but there was no difference in the CD4-lymphocyte subset (p = 0.4928).
Conclusions
Our results are similar to the ones reported in non-oncologic population, such as an increased number of NK-lymphocytes in elderly patients and a lower count of B-lymphocytes. Therefore, signs of immunosenescence can be seen in patients with NSCLC. However, subpopulations of lymphocytes show more accurately cell functionality. This is why we are performing deeper research regarding the changes in immune system produced with age in oncologic patients.
Legal entity responsible for the study
Doctor Peset University Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
46P - Inflamed human oropharyngeal cancers with ongoing tumor-specific T cell responses comprise a different type of immune suppressive T cells (ID 259)
- S. J. Santegoets (Leiden, Netherlands)
- S. J. Santegoets (Leiden, Netherlands)
- C. L. Duurland (Leiden, Netherlands)
- E. S. Jordanova (Leiden, Netherlands)
- V. J. Van Ham (Leiden, Netherlands)
- I. Ehsan (Leiden, Netherlands)
- M. J. Welters (Leiden, Netherlands)
- S. H. Van der Burg (Leiden, Netherlands)
Abstract
Background
Recent studies have shown that for optimal immune suppression regulatory T cells (Tregs) are required to adopt a transcriptional profile similar to that of the type of T cells they aim to suppress. For instance, Foxp3+ Tregs upregulate the Th1-associated transcription factor Tbet to control a type 1 cytokine-mediated inflammatory response in order to prevent unwanted tissue destruction and immunopathology. However, little is known about the existence and function of such Treg cells in cancer patients.
Methods
To study the presence and potential impact of Tbet-expressing Foxp3+ (Foxp3+Tbet+) Tregs in human cancer, we applied three-color immunofluorescence staining and 12-parameter flow cytometry on the tumor microenvironment (TME) of human papilloma virus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) patients.
Results
Our data revealed that Foxp3+Tbet+ Tregs accumulate and dominate in the tumor cell nests of patients with a concomitant HPV-specific and type 1-oriented intratumoral T cell infiltrate. Moreover, these CD4+CD25+CD127–Foxp3+Tbet+ Tregs exhibited an activated phenotype and co-expressed high levels of CTLA4 and Helios. Assessment of the methylation status of the FoxP3 gene locus TSDR of flow cytometry-sorted Foxp3+Tbet+ and Foxp3+Tbet - Tregs revealed that it was maximally demethylated, indicating that these Tregs have the full capacity to suppress immune cells. Interestingly, OPSCC patients with high intratumoral frequencies of Foxp3+Tbet+ Tregs, but not Foxp3+Tbet– Tregs, displayed prolonged disease-specific survival, suggesting that the presence of Foxp3+Tbet+ Tregs is a reflection of a strong and clinically favorable local tumor-specific type 1 immune response.
Conclusions
In conclusion, bona fide Foxp3+Tbet+ regulatory T cells accumulate in HPV16-driven tumors that are highly infiltrated with type 1 tumor-specific T cells, at levels enough to impede full spontaneous immune-mediated tumor control.
Legal entity responsible for the study
Sjoerd H. van der Burg.
Funding
The Dutch Cancer Society.
Disclosure
All authors have declared no conflicts of interest.
84P - Safety and clinical outcome in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer treated with the CXCL12 inhibitor NOX-A12 in combination with PD-1 checkpoint inhibitor pembrolizumab (ID 463)
- N. Halama (Heidelberg, Germany)
- N. Halama (Heidelberg, Germany)
- U. Prüfer (Heidelberg, Germany)
- A. Frömming (Berlin, Germany)
- D. Beyer (Berlin, Germany)
- D. Eulberg (Berlin, Germany)
- J. Jungnelius (Berlin, Germany)
- A. Mangasarian (Berlin, Germany)
Abstract
Background
NOX-A12 is an inhibitor of the chemokine CXCL12 for treatment of solid tumors. Binding of CXCL12 by NOX-A12 prevents receptor engagement and blocks the ability of CXCL12 to form a chemotactic concentration gradient. The Opera study (NCT03168139) is a Phase 1/2 study to evaluate pharmacodynamic effects and safety of monotherapy with NOX-A12 as well as safety and efficacy of a combination of NOX-A12 with pembrolizumab in metastatic microsatellite-stable colorectal (CRC) and pancreatic (PaC) cancer.
Methods
Patients received 300 mg NOX-A12 twice weekly during the two-week monotherapy phase. Biopsies were taken from liver metastases before treatment and after NOX-A12 monotherapy for analysis of immune cell infiltration and cytokine signature. In the combination phase, patients received repeated 21-day cycles of 300 mg NOX-A12 and 200 mg pembrolizumab.
Results
20 patients were recruited, thereof 11 with CRC and 9 with PaC. 15 of the patients (75%) are male, with a median age of 62 (CRC) and 68 years (PaC). Patients were heavily pretreated with a median of 5 (CRC) and 3 lines (PaC) of prior treatment. Known best responses to last prior treatment was PD for 16 out of 20 patients. The AE profile was comparable with the pembrolizumab profile or typical for the underlying diseases. Thus far, 5 of the patients (25%) achieved a stable disease (3 CRC and 2 PaC). Interestingly, some of the patients with SD or clinical benefit also showed a favorable tissue cytokine response upon NOX-A12 monotherapy. Higher changes of CXCL12 levels in tissue observed upon monotherapy – indicating more complete CXCL12 neutralization – correlated with a favorable cytokine profile.
Conclusions
NOX-A12 alone and combined with pembrolizumab was safe and well tolerated. Changes in the cytokine signature in tumor tissue suggest that NOX-A12 modulates the tumor microenvironment and induces an immune-stimulatory Th1-like signature in multiple patients of which some show signs of disease stabilization or clinical benefit. The observed time of treatment compares favorably with the expected clinical course of such end-stage and heavily pre-treated patient population.
Clinical trial identification
EudraCT: 2016-003657-15.
Legal entity responsible for the study
Noxxon Pharma.
Funding
Noxxon Pharma AG.
Disclosure
N. Halama, U. Prüfer: Research funded by Noxxon Pharma AG. A. Frömming, D. Beyer, D. Eulberg, J. Jungnelius, A. Mangasarian: Employee of Noxxon Pharma AG.
New directions in CAR therapy (ID 12)
- F. Thistlethwaite (Manchester, United Kingdom)
- F. Thistlethwaite (Manchester, United Kingdom)
LBA4 - Long-term follow-up in the KEYNOTE-010 study of pembrolizumab (pembro) for advanced NSCLC, including in patients (pts) who completed 2 years of pembro and pts who received a second course of pembro (ID 479)
- R. Herbst (New Haven, CT, United States of America)
- R. Herbst (New Haven, CT, United States of America)
- E. B. Garon (Santa Monica, CA, United States of America)
- D. Kim (Seoul, Korea, Republic of)
- B. Chul Cho (Seoul, Korea, Republic of)
- J. Pérez Gracia (Pamplona, Spain)
- J. Han (Goyang-si, Korea, Republic of)
- C. Dubos Arvis (Caen, France)
- M. Majem (Barcelona, Spain)
- M. Forster (London, United Kingdom)
- I. Monnet (Créteil, France)
- S. Novello (Orbassano, Italy)
- Z. Szalai (Gyor, Hungary)
- M. A. Gubens (San Francisco, CA, United States of America)
- W. Su (Tainan, Taiwan)
- G. L. Ceresoli (Bergamo, Italy)
- A. Samkari (Kenilworth, NJ, United States of America)
- E. Jensen (Kenilworth, NJ, United States of America)
- G. M. Lubiniecki (Kenilworth, NJ, United States of America)
- P. Baas (Amsterdam, Netherlands)
Abstract
Background
In the global, open-label, phase 2/3 study KEYNOTE-010, pembro 10 mg/kg or 2 mg/kg Q3W improved OS vs docetaxel in pts with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1% (coprimary analyses) at median follow-up of 13.1 mo. We present long-term results overall, in pts who completed 35 cycles (∼2 y) of pembro, and in pts who received a second course of pembro.
Methods
Pts aged >18 y with previously treated advanced NSCLC with PD-L1 TPS ≥1% were randomized 1:1:1 to pembro 10 mg/kg or 2 mg/kg Q3W, or docetaxel 75 mg/m2 Q3W. Pts received pembro for 35 cycles, until disease progression/intolerable toxicity. Response was assessed every 9 wk (RECIST 1.1 by independent central review), and survival every 2 mo posttreatment. There was no difference between pembro doses in the primary analysis, thus doses were pooled in this analysis.
Results
As of March 16, 2018, median (range) follow-up was 42.6 (35.2–53.2) mo overall (N = 1033). Pembro improved OS vs docetaxel in pts with PD-L1 TPS ≥50% (HR, 0.53; 95% CI, 0.42–0.66; P < 0.00001) and TPS ≥1% (HR, 0.69; 95% CI, 0.60–0.80; P < 0.00001). In pts with PD-L1 TPS ≥50%, median (95% CI) OS was 16.9 (12.3–21.4) mo with pembro vs 8.2 (6.4–9.8) mo with docetaxel; 36-mo OS rates were 35% vs 13%, respectively. Similar to the primary analysis, 16% of pembro pts and 36% of docetaxel pts had grade 3–5 treatment-related AEs. 79 of 690 pembro pts received 35 treatment cycles (∼2 y). 36-mo OS rate among these 79 pts was 99% and 75 (95%) had PR/CR as best response; 72 pts (91%) remained alive. 48 pts (64%) had an ongoing response; median duration of response was not reached (range, 4–46+ mo). 25 of 79 pts (32%) had PD (investigator review) after stopping 35 cycles of pembro. 14 pts received second course pembro, 5 of whom completed 17 cycles; 6 (43%) had PR, 5 (36%) had SD, and 11 (79%) remained alive.
Conclusions
At 43-mo follow-up, pembro continued to prolong OS vs docetaxel in pts with previously treated, PD-L1–expressing advanced NSCLC, with manageable long-term safety. Most pts who completed 35 cycles (∼2 y) of pembro had durable response. The majority of pts with PD by investigator review who received second course pembro had either PR or SD and remained alive.
Editorial acknowledgement
Medical writing and editorial assistance was provided by C4 MedSolutions, LLC (Yardley, PA), a CHC Group company. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Clinical trial identification
NCT01905657.
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
R.S. Herbst: Consulting role: Eli Lilly, Genentech/Roche, Merck, NextCure, Novartis, Pfizer; Research support: AstraZeneca, Eli Lilly, Merck. E.B. Garon: Funding to institution: Merck & Co., Inc., AstraZeneca, Eli Lilly, Genentech, Bristol-Myers Squibb, Pfizer, Novartis, Mirati. B. Chul Cho: Honoraria: AstraZeneca, Roche, Boehringer Ingelheim; Research funding: Bayer, AstraZeneca, Yuhan, Novartis; Consultant or advisor: AstraZeneca, Roche, Boehringer Ingelheim; Speakers’ bureau: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis. J.L. Pérez Gracia: Grants: Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, Lilly; Advisor, speakers’ bureau: Bristol-Myers Squibb, Roche. J-Y. Han: Honoraria: AstraZeneca, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme; Research funding: Roche; Consultant or advisor: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Eli Lilly. M. Majem: Consultant or advisor: AstraZeneca, Roche, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis. M. Forster: Research grants: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck; Honoraria for advisory and consultancy roles: Achilles, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, PharmaMar, Roche. I. Monnet: Congress invitations: Roche, AstraZeneca. S. Novello: Funding to institution: Merck Sharp & Dohme; Speakers bureau: Eli Lilly, Takeda, Roche, AstraZeneca, Merck Sharp & Dohme, Boehringer Ingelheim. M.A. Gubens: Research grant to institution: Merck & Co., Inc.; Personal fees for consulting: AbbVie, Ariad, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera, Clovis, Genentech-Roche, Mersana, Nektar, Novartis, Pfizer. A. Samkari, E. Jensen, G.M. Lubiniecki: Employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. P. Baas: Consulting role: Genentech/Roche, Merck, Bristol-Myers Squibb, Pfizer; Research support: Bristol-Myers Squibb, Roche, Merck. All other authors have declared no conflicts of interest.