Introduction to immunotherapy in cancer Educational session

Immune checkpoints: Do we really know how they work? (ID 234)

Lecture Time
11:55 - 12:15
Speakers
  • J. B. Haanen (Amsterdam, Netherlands)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2018
Time
11:15 - 12:45
Authors
  • J. B. Haanen (Amsterdam, Netherlands)
Poster Display session Poster Display session

62P - First-line systemic real-world treatment of patients with advanced/metastatic NSCLC in the UK (ID 308)

Presentation Number
62P
Lecture Time
12:30 - 12:30
Speakers
  • M. Wang (Uxbridge, United Kingdom)
Session Name
Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
14.12.2018
Time
12:30 - 13:00
Authors
  • M. Wang (Uxbridge, United Kingdom)
  • P. Dhokia (Uxbridge, United Kingdom)
  • S. Menon (London, United Kingdom)
  • B. Martindale (Collegeville, United States of America)

Abstract

Background

Immuno-oncology (IO) has changed treatment (Tx) landscape of non-small cell lung cancer (NSCLC). IO is efficacious and a less toxic alternative to standard chemotherapy in treating NSCLC. This study analysed 1st line (1L) Tx patterns of patients with stage IIIb/IV NSCLC in real-world setting.

Methods

IQVIA Oncology Dynamics (OD) database was used to identify stage IIIb/IV NSCLC patients who initiated and received 1L Tx between June 2017 and March 2018 in the UK. IQVIA OD is a syndicated database collecting longitudinal, anonymized, patient-level oncology data through a quarterly physician panel survey. The UK panel characteristics were: 94% public, 65% university, 12% Scotland/Northern Ireland - 6% Wales - 82% England. The response rate ranged 13-72% among circa 225 physicians per quarterly pulse. Data on patient/disease characteristics, Tx, and biomarkers were extracted and analysed.

Results

In total, data from 738 stage IIIb/IV NSCLC patients receiving 1L cancer Tx were analysed. At questionnaire completion, 57% of patients were male and 68% were aged >60 years. Most patients had cancers with non-squamous histology (79%); fewer had squamous (20%) and other (1%). ECOG performance status was assessed as 0 in 14% and 1 in 76% of patients, and metastases were mostly found in the lung (49%), bone and liver (34% each), lymph nodes local (36%) and distant (25%). COPD was the most common comorbidity (28%); 40% of patients reported none. 49% were former smokers and 22% current smokers. Chemotherapy and targeted therapies were the most frequent 1L Tx received by 301 (41%) and 219 (30%) patients, respectively. 30% of patients (n = 218) received IO Tx in 1L; pembrolizumab was the most common IO therapy (n = 216, 29%). PD-L1 testing was performed among 76% of the latest quarter patients (n = 195/255); 106 (54%) were positive (PD-L1+; ≥50%), 82 (42%) negative (PD-L1-; <50%) and 7 awaiting results. Most PD-L1+ patients received pembrolizumab in 1L (86%), whereas PD-L1- patients were mostly treated with chemotherapy (73%) and one third received targeted therapies.

Conclusions

In the current UK treatment landscape for stage IIIb/IV NSCLC, only 30% of patients were treated with IO Tx in 1L. A high proportion of 1L patients is still treated with traditional chemotherapy.

Editorial acknowledgement

Editorial assitance was provided by Eleonora Morais from IQVIA.

Legal entity responsible for the study

Outcome Sciences LLC (an IQVIA company).

Funding

Bristol-Myers Squibb Pharmaceuticals LTD.

Disclosure

M. Wang: Employee of Bristol-Myers Squibb Pharmaceuticals Ltd. S. Menon, B. Martindale: Employee of IQVIA (IQVIA Oncology Dynamics, a syndicated database collecting oncology data).

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Poster Display session Poster Display session

97P - Circulating RNAs in advanced colorectal cancer patients reveal increased expression of PD-1 with conventional CRC therapy (ID 347)

Presentation Number
97P
Lecture Time
12:30 - 12:30
Speakers
  • M. Nasrullah (Jeddah, Saudi Arabia)
Session Name
Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
14.12.2018
Time
12:30 - 13:00
Authors
  • M. Nasrullah (Jeddah, Saudi Arabia)
  • M. Bakhrebah (Riyadh, Saudi Arabia)
  • M. Hassan (Jeddah, Saudi Arabia)
  • A. Alghamdi (Jeddah, Saudi Arabia)
  • W. Abdulaal (Jeddah, Saudi Arabia)
  • M. Zamzami (Jeddah, Saudi Arabia)
  • A. Ghafari (Jeddah, Saudi Arabia)
  • M. Khan (Jeddah, Saudi Arabia)
  • H. Choudhry (Jeddah, Saudi Arabia)

Abstract

Background

Colorectal cancer (CRC) is the third most diagnosed cancer among men and second among women globally. Generally, with age, the risk of this cancer grows and is happened by various genetic alterations. The immune system plays an important role against CRC and that provides a new means to CRC therapy. Our research is focused on the relative expression level of ten different immune genes namely IFNγ, CD 273, CD274, PD-1, β2M, CD3e, CD28, HLA-A, ICAM 1, and CTLA 4 which are known to play important role in immune regulation during different cancers. We hypothesize that the expression of the above-mentioned genes will be altered during CRC and therapy will promote the expression of genes involved in the activation of immune system.

Methods

RNA was extracted from the whole blood sample of CRC patient (n = 50) and normal (n = 34) volunteers. Then cDNA was synthesized, and RNase inhibitor was used. Specific primers for all these genes were designed. Later, RT-qPCR has been done using SYBR® green master mix. Patient demographics were also recorded. All tested genes have been normalized to a housekeeping gene, RPL11. Values of relative expression for all genes were calculated using REST 2009 software.

Results

Among screened genes, CD 273, CD274, and CTLA 4 were not expressed while, IFNγ, PD-1, β2M, CD3e, CD28, HLA-A, and ICAM 1 found expressed in CRC. After comparing the gene expression of advanced CRC patients with normal control, PD-1 found upregulated (P < 0.045). Clinicopathological correlation revealed PD-1 is highly expressed (P < 0.001) in advance stage of CRC patients upon treatment with both chemotherapy and immunotherapy (capecitabine, oxaliplatin, irinotecan hydrochloride, folinic acid, fluorouracil, and bevacizumab).

Conclusions

Our study indicates significant induction of PD-1 at the advanced stage of CRC and during therapy. It suggests that conventional therapies for CRC must be modulated and/or a combination of therapy with anti PD-1 drug should be conducted for the better clinical outcome of CRC.

Legal entity responsible for the study

Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Funding

King Abdulaziz City for Science and Technology.

Disclosure

All authors have declared no conflicts of interest.

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Biomarkers (host related) Educational session

Mining the microbiomes for biomarkers in cancer immune therapy (ID 15)

Lecture Time
16:30 - 16:50
Speakers
  • J. Wargo (Houston, United States of America)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2018
Time
16:30 - 18:00
Authors
  • J. Wargo (Houston, United States of America)
What’s new in chest tumours Educational session

Immunotherapy in locally advanced NSCLC (ID 37)

Lecture Time
14:55 - 15:15
Speakers
  • E. Felip (Barcelona, Spain)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
14.12.2018
Time
14:15 - 15:45
Authors
  • E. Felip (Barcelona, Spain)
What’s new in genitourinary (GU) tumours Educational session

Session DOI (ID 511)

Lecture Time
09:10 - 09:10
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
15.12.2018
Time
09:10 - 10:40
Immuno-oncology endpoints for approval: The case of tumor agnostic approval for MSI-H cancers Panel Discussion

Discussion led by Chairs (ID 187)

Lecture Time
08:20 - 09:00
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
16.12.2018
Time
08:00 - 09:00
Poster Display session Poster Display session

19P - Signs of immunosenescence in patients diagnosed with non-small cell lung cancer (ID 269)

Presentation Number
19P
Lecture Time
12:30 - 12:30
Speakers
  • T. Soria Comes (Valencia, Spain)
Session Name
Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
14.12.2018
Time
12:30 - 13:00
Authors
  • 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.

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What’s new in brain tumours Educational session

Session DOI (ID 501)

Lecture Time
11:00 - 11:00
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
16.12.2018
Time
11:00 - 12:30
Poster Display session Poster Display session

53P - Immune-related adverse events correlate with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access programme (ID 239)

Presentation Number
53P
Lecture Time
12:30 - 12:30
Speakers
  • E. Baldini (Lucca, Italy)
Session Name
Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
14.12.2018
Time
12:30 - 13:00
Authors
  • E. Baldini (Lucca, Italy)
  • A. Lunghi (Vallo della Lucania, Italy)
  • E. Cortesi (Rome, Italy)
  • D. Turci (Ravenna, Italy)
  • M. C. Garassino (Milan, Italy)
  • V. Stati (Roma, RM, Italy)
  • A. Ardizzoni (Bologna, Italy)
  • B. Ricciuti (Perugia, (PG), Italy)
  • A. Frassoldati (Ferrara, Italy)
  • G. Romano (Lecce, Italy)
  • A. Illiano (Napoli, Italy)
  • F. Verderame (Palermo, Italy)
  • G. Fasola (Udine, Italy)
  • P. Marchetti (Roma, Italy)
  • C. Pinto (Reggio Emilia, Italy)
  • G. Carteni (Lucca, Italy)
  • V. Scotti (Firenze, Italy)
  • C. Tibaldi (Carrara, Italy)
  • L. Fioretto (Firenze, Italy)
  • D. Giannarelli (Roma, Italy)

Abstract

Background

The incidence of any and of severe grade immune-related adverse events (irAEs) with second-line Nivolumab (N) monotherapy is 26% and 6% respectively. While potentially serious and even fatal, in the absence of appropriate therapy, such events might be an indicator of the activation of the immune system and, potentially, of efficacy.

Methods

We collected the records of 1.959 NSCLC patients (pts) including those with Squamous (S) and non-Squamous (non-S) histology, treated with N in the Italian expanded access programme and we recorded the appearance of any and of severe grade irAEs. We then retrospectively searched for potential correlations between this type of toxicity and efficacy parameters by using cox regression analysis.

Results

A total of 1.585 and 374 pts had non-S and S cell carcinoma respectively and 57% received N as second-third line of therapy. Overall 342 (17.8%) developed an irAE of any grade. We observed that pts developing any grade irAE achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9-7.1] vs 3.0 [95% CI: 2.8-3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5-19.9] vs 9.4 [95% CI: 8.4-10.4], p < 0.00001) compared to pts who did not. IrAEs correlate with clinical outcomes in both non-S and S histology. At multivariate analysis the development of an irAE remained an independent indicator of N efficacy (HR 1.44[95% CI: 1.22-1.71] p < 0.0001).

Conclusions

This is the first report performed in a large series of Caucasian NSCLC pts showing that the activation of the immune system induced by N and documented by the appearance of irAEs correlates with outcome. A careful management of pts with such an event could lead to a maximum clinical benefit.

Legal entity responsible for the study

Editta Baldini.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session Poster Display session

48TiP - A phase II study of autologous tumor infiltrating lymphocytes (TIL; LN-144/LN-145) in patients with solid tumors (ID 472)

Presentation Number
48TiP
Lecture Time
12:30 - 12:30
Speakers
  • J. Chesney (Louisville, KY, United States of America)
Session Name
Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
14.12.2018
Time
12:30 - 13:00
Authors
  • J. Chesney (Louisville, KY, United States of America)
  • A. Cacovean (San Carlos, United States of America)
  • H. Li (San Carlos, CA, United States of America)
  • D. Barton (San Carlos, CA, United States of America)
  • M. Fardis (San Carlos, CA, United States of America)

Abstract

Background

Adoptive cell therapy with TIL has demonstrated durable complete responses in immunogenic tumors with high mutational burden in patients who had not received prior checkpoint therapy (>22% CR). Pembrolizumab is an approved agent for treatment of metastatic melanoma and head and neck cancers. Further, checkpoint inhibitors have been reported to possibly enhance the efficacy of TIL therapy. One aim of this study is to improve on the efficacy response for early line patients by combining TIL with anti-PD1 in metastatic melanoma and head and neck cancers (Cohorts 1 and 2). In Cohort 3, TIL alone is offered to non-small cell lung cancer patients who have received prior systemic therapy including checkpoint inhibitors.

Trial design

IOV-COM-202 is a Phase 2 multicenter, open-label, nonrandomized study in which patients are enrolled in the combination arms (Cohorts 1 and 2) or LN-145 therapy only (Cohort 3) based upon study disease (see above). Planned enrollment is N = 36 (12/cohort). Tumors resected at local institutions are processed at centralized GMP facilities using a 22-day manufacturing process to generate the final cryopreserved infusion product (LN-144/LN-145) that is shipped to the sites. All patients receive TIL therapy consisting of 1 week of a preconditioning cyclophosphamide/fludarabine lymphodepletion regimen, followed by a single infusion of LN144/LN-145 (Day 0) and up to 6 doses of intravenous IL-2 (600,000 IU/kg). Patients in Cohorts 1 and 2 also receive pembrolizumab on Day 1 and again every 3 weeks for up to 2 years. Eligibility includes: ≥ 18 years of age; 1-3 lines of prior systemic therapy (exclusions apply); ≥ 1 resectable lesion(s) yielding ≥ 1.5 cm in diameter of viable tumor and a remaining RECIST-measurable lesion; and ECOG PS of 0-1. For each cohort, the primary endpoint is ORR per RECIST v1.1 and safety. Secondary endpoints are CR rate, DOR, DCR, PFS, and OS. Exploratory objectives include tumor response per irRECIST, immune correlates of response, and HRQoL. NCT03645928

Legal entity responsible for the study

Iovance Biotherapeutics, Inc.

Funding

Iovance Biotherapeutics, Inc.

Disclosure

A. Cacovean, D. Barton: Employee of Iovance Biotherapeutics, Inc. M. Fardis: Chief Executive Officer of Iovance Biotherapeutics, Inc. All other authors have declared no conflicts of interest.

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Poster Display session Poster Display session

88P - Run-in-phase results from a multicenter phase II trial to evaluate pembrolizumab (P) and gemcitabine (Gem) in patients (pts) with HER2-negative advanced breast cancer (ABC): GEICAM/2015-04 PANGEA-Breast (ID 342)

Presentation Number
88P
Lecture Time
12:30 - 12:30
Speakers
  • V. Quiroga (Madrid, Spain)
Session Name
Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
14.12.2018
Time
12:30 - 13:00
Authors
  • V. Quiroga (Madrid, Spain)
  • E. Holgado (Madrid, Spain)
  • J. Alonso (Murcia, Spain)
  • R. Andres (Zaragoza, Spain)
  • F. Moreno Anton (Madrid, Spain)
  • M. Alamo De La Gala (Sevilla, Spain)
  • F. Henao (Sevilla, Spain)
  • B. Cirauqui Cirauqui (Badalona, Barcelona, Spain)
  • M. Margeli (Badalona, Spain)
  • J. Cortes Castan (Barcelona, Spain)
  • M. Gion Cortes (Madrid, Spain)
  • A. Soto (Murcia, Spain)
  • S. Benito (Madrid, Spain)
  • M. Escudero (San Sebastian de los Reyes, Spain)
  • M. Chiesa (San Sebastian de los Reyes, Spain)
  • R. Caballero (San Sebastian de los Reyes, Madrid, Spain)
  • S. Bezares Montes (San Sebastian de los Reyes, Madrid, Spain)
  • E. M. Carrasco (San Sebastian de los Reyes, Spain)
  • L. De La Cruz Merino (Sevilla, Spain)

Abstract

Background

This trial is based on a combination strategy with two immunostimulatory agents in the search of synergism that may induce responses with long term clinical benefit in ABC pts. Here, we report the results from the run-in-phase of the study (ClinicalTrials.gov Identifier: NCT03025880).

Methods

HER2-negative ABC pts previously treated with anthracyclines and taxanes (unless contraindicated) and ≥ 2 lines of hormone therapy, if hormone receptor (HR)-positive disease, were eligible. Treatment consisted of 21-day cycles (cy) of P 200mg on day 1 and Gem on days 1 and 8. A 6 + 6 design was used with 2 dose levels (DL) of Gem: 1250mg/m2 (DL0) and 1000mg/m2 (DL1). The primary objective was to define the Recommended Phase II Dose (RP2D) based on dose limiting toxicities (DLT) during the first cy (<33% of pts with a DLT); secondary objectives included evaluation of safety and efficacy. Pts were treated until progression, or unacceptable toxicity whatever occurs first.

Results

Fourteen pts were included in DL0; 3 pts were replaced due to early progressive disease (PD). DL1 was not explored as DL0 was considered the RP2D . Median age was 48 years (range 32-61), and 9 pts had triple negative disease. The majority of pts had an ECOG performance status ≤ 1 (n = 13) and visceral involvement (n = 12); 8 pts had ≤2 involved sites. Median number of prior lines (any therapy) for metastatic disease was 3 (range 1-7). Pts received a median of 4.5 cy of Gem (range 1-11) and 3 cy of P (range 1-11). One DLT was observed, Gem dose omission on day 8 due to grade (G) 2 thrombocytopenia. G ≥ 3 adverse events (AEs) related to the treatment were reported on 5 pts; G4 AEs included thrombocytopenia and lymphopenia (7.1% each); G3 AEs included neutropenia (14.3%), anemia, leukopenia, thrombocytopenia, diarrhea and transaminases increase (7.1% each). The best overall tumor response was stable disease on 3 pts at the time of this analysis; 9 pts discontinued treatment due to PD, 1 pt due to respiratory failure, and 2 pts died of breast cancer. Twenty-two pts have been included on the ongoing phase II part.

Conclusions

P can be safely combined with Gem. P 200mg and Gem 1250mg/m2 was declared as the RP2D.

Clinical trial identification

NCT03025880.

Legal entity responsible for the study

GEICAM, Spanish Breast Cancer Group.

Funding

Merck Sharp & Dohme Corp (MSD).

Disclosure

J. Cortes Castan: Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer. Consulting/advisor: Roche, Celgene, AstraZeneca, Cellestia Biotech, Biothera, Merus, Seattle Genetics.  E.M. Carrasco: Husband: Honoraria: Pfizer. All other authors have declared no conflicts of interest.

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