Displaying One Session

Room C Mini Oral session
Date
13.12.2019
Time
08:00 - 09:00
Location
Room C
Chairs
  • M. Donia (Herlev, Denmark)
  • P. Romero (Epalinges, Switzerland)
Mini Oral session 2 Mini Oral session

DOI session

Lecture Time
08:00 - 08:00
Session Name
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2019
Time
08:00 - 09:00
Mini Oral session 2 Mini Oral session

2O - Biomarkers of immune switch induced by a novel anti-macrophage antibody (anti-Clever-1 mAb; FP-1305) in MATINS trial patients with advanced solid tumours

Presentation Number
2O
Lecture Time
08:00 - 08:05
Speakers
  • M. Hollmén (Turku, Finland)
Session Name
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2019
Time
08:00 - 09:00
Authors
  • M. Hollmén (Turku, Finland)
  • R. Virtakoivu (Turku, Finland)
  • P. Jaakkola (Helsinki, Finland)
  • A. Minchom (London, United Kingdom)
  • S. Jalkanen (Turku, Finland)
  • M. Karvonen (Turku, Finland)
  • J. Mandelin (Turku, Finland)
  • J. Koivunen (Oulu, Switzerland)
  • P. Bono (Helsinki, Finland)

Abstract

Background

A scavenger receptor CLEVER-1 is highly expressed on tumor associated macrophages (TAMs) and mediates the clearance of “unwanted” self-components. Pre-clinical studies demonstrate that CLEVER-1 inhibition increases TAM pro-inflammatory cytokine secretion and antigen presentation reactivating CD8+ T cell responses with robust anti-tumor activity (Viitala et al., 2019). Targeting CLEVER-1 could overcome the immunosuppressive tumor microenvironment and has led to the development of FP-1305, a humanized anti-CLEVER-1 IgG4-antibody.

Methods

MATINS (Macrophage Antibody To INhibit immune Suppression) trial is a multicenter first-in-human phase I/II study (NCT03733990) to assess the tolerability, safety and preliminary efficacy of FP-1305 in patients with advanced, IO-refractory melanoma, cholangiocarcinoma, hepatocellular, colorectal, and pancreatic ductal adenocarcinoma. Biomarker analysis included CLEVER-1 determination, immune cell profiling by mass cytometry and analysis of cytokine production.

Results

11 patients (median age 57) were enrolled in four cohorts (0.3, 1.0, 3.0 or 10 mg/kg) and received 1-8 cycles (median 3) of FP-1305 every three weeks. FP-1305 has been well tolerated without dose-limiting toxicities and maximum tolerated dose (MTD) has not been reached. Promising early efficacy results have recently been reported (ESMO 2019, LBA19). FP-1305 dosing led to increased Th1 skewing (CXCR3+CCR6-) of CD4 and CD8 T cell populations with downregulation of several inhibitory immune checkpoint molecules. Increase in circulating IFN gamma was detected but it was most prominent in the patient showing durable partial response.

Conclusion

FP-1305 is the first macrophage checkpoint inhibitor candidate promoting immune switch with promising tolerability and clinical anti-tumor activity. FP-1305 represents a novel treatment option to provoke immune response against cold tumors.

Clinical trial identification

NCT03733990.

Legal entity responsible for the study

Faron Pharmaceuticals.

Funding

Finnish Academy, Finnish Cancer Foundations, Sigrid Juselius Foundation, Faron Pharmaceuticals.

Disclosure

M. Hollmén: Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Faron Pharmaceuticals. P. Jaakkola: Advisory / Consultancy: Faron Pharmaceuticals. A. Minchom: Advisory / Consultancy: Faron Pharmaceuticals. S. Jalkanen: Shareholder / Stockholder / Stock options: Faron Pharmaceuticals. M. Karvonen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Faron Pharmaceuticals. J. Mandelin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Faron Pharmaceuticals. J. Koivunen: Advisory / Consultancy: Faron Pharmaceuticals; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Boehringer-Ingelheim; Advisory / Consultancy: KaikuHealth. P. Bono: Advisory / Consultancy, Travel / Accommodation / Expenses, Spouse / Financial dependant: Faron Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: OrionPharma. All other authors have declared no conflicts of interest.

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Mini Oral session 2 Mini Oral session

3O - A pre-existing inflammatory immune microenvironment predicts the clinical and immunological response of vulvar high-grade squamous intraepithelial lesions to therapeutic HPV16 peptide vaccination

Presentation Number
3O
Lecture Time
08:05 - 08:10
Speakers
  • Z. Abdulrahman (Leiden, Netherlands)
Session Name
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2019
Time
08:00 - 09:00
Authors
  • Z. Abdulrahman (Leiden, Netherlands)
  • N. De Miranda (Leiden, Netherlands)
  • M. Van Poelgeest (Leiden, Netherlands)
  • S. Van der Burg (Leiden, Netherlands)

Abstract

Background

Vulvar High-grade Squamous Intraepithelial Lesion (vHSIL) is predominantly induced by high-risk Human Papilloma Virus type 16 (HPV16). In two independent trials, therapeutic vaccination against the oncoproteins of HPV16 with synthetic long peptides (SLP) resulted in vHSIL regression in about half of the patients after 12 months. Several studies have shown that the immune microenvironment influences therapy outcome. Therefore, a thorough investigation of the vHSIL immune microenvironment before and after SLP vaccination was performed, and its impact on clinical response was studied.

Methods

Two novel multiplex immunofluorescence panels were designed for formalin-fixed paraffin-embedded tissue, one for T cells (CD3, CD8, FoxP3, Tim3, Tbet, PD-1, DAPI) and one for myeloid cells (CD14, CD33, CD68, CD163, CD11c, PD-L1, DAPI). Pre- and 3 months post-vaccination biopsies of 29 patients and 27 healthy vulva excisions were stained, scanned with the Vectra multispectral imaging system, and automatically phenotyped and counted with inForm advanced image analysis software.

Results

A pre-existing pro-inflammatory TME, marked by high numbers of CD4 and CD8 T cells expressing Tbet and/or PD-1 as well as CD14+ inflammatory macrophages, is a strong predictor for good clinical response. A clear stepwise increase in pre-vaccination infiltrating Tbet+, CD4+, CD8+ T cells and CD14+ macrophages, and decrease in Foxp3+ Tregs was observed as response increased from non to partial to complete response. Moreover, the pre-vaccination immune microenvironment of complete responders resembled healthy vulva. Vaccination further increased infiltrating CD4+ and Tbet+ T cells and CD14+ macrophages and decreased FoxP3+ Tregs in the complete and partial responders, but not in the non responders.

Conclusion

Clinical responsiveness to therapeutic HPV16 SLP vaccination requires a pre-existing inflamed type 1 immune contexture in vHSIL. Hence, only patients with an inflamed TME should be selected for monotherapy by therapeutic vaccination, since this strategy is incapable of creating an inflamed TME in patients where this is absent.

Legal entity responsible for the study

The authors.

Funding

Leiden University Medical Center.

Disclosure

S.H. van der Burg: Advisory / Consultancy: ISA Pharmaceuticals. All other authors have declared no conflicts of interest.

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Mini Oral session 2 Mini Oral session

130O - Association of long non-coding RNA biomarkers with clinically immune subtype and prediction of immunotherapy in patients with cancer

Presentation Number
130O
Lecture Time
08:10 - 08:15
Speakers
  • Y. Yu (Guangzhou, China)
Session Name
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2019
Time
08:00 - 09:00
Authors
  • Y. Yu (Guangzhou, China)
  • W. Zhang (Zhanjiang, China)
  • A. Li (Zhanjiang, China)
  • Y. Chen (Guangzhou, China)
  • Y. Wang (Guangzhou, China)
  • Y. Zhang (Guangzhou, China)
  • Z. He (Guangzhou, China)
  • Q. Ou (Guangzhou, China)
  • R. Liu (Zhanjiang, China)
  • E. Song (Guangzhou, China)
  • H. Yao (Guangzhou, China)

Abstract

Background

Long non-coding RNAs (lncRNAs) are involved in innate and adaptive immunities in cancers by mediating the functional states of immunologic cells, pathways, and genes. However, whether lncRNAs could serve as effective biomarkers for molecular classification and prediction of cancer immunotherapy efficacy are largely unknown.

Methods

This study analyzed lncRNA and genomic data of 348 atezolizumab-treated bladder cancer patients from phase II IMvigor 210 trial and 3,021 patients in lung cancer, breast cancer, bladder cancer, and melanoma cohorts from The Cancer Genome Atlas. We investigated lncRNA-based immune subtypes associated with cancer immunotherapy efficacy. We built a novel lncRNA score using computational algorithms and integrated it with programmed-death ligand 1 (PD-L1) expression and tumor mutation burden (TMB) to achieve accurate immunotherapeutic prediction.

Results

The results from IMvigor 210 trial showed that four distinct microenvironment-based subtypes characterized by lncRNA expression and tumor specific cytotoxic T lymphocytes (CTLs) infiltration had significant difference in overall survival (OS) (hazard ratio [HR] 0.77, 95%CI 0.67–0.88; P = 0.0002), with the greatest benefits in Immune-Active Class, followed by Immune-Exclusion Class, Immune-Dysfunctional Class, and Immune-Desert Class. High NKILA lncRNA expression was identified as a negative predictor of immunotherapeutic OS benefits and a critical regulator of dysfunctional immune response. Patients with low- versus high- lncRNA scores were associated with significantly longer OS in IMvigor 210 trial (HR 0.32, 95% CI 0.24–0.42; P < 0.0001) and across various cancer types. Multiomics comprising lncRNA score, PD-L1 expression and TMB led to more precise OS prediction in IMvigor 210 trial (20-month AUC=0.80) and in melanoma immunotherapy cohort (24-month AUC=0.89) compared with variable alone.

Conclusion

We suggested immunotherapy for patients in Immune-Functional Class, especially for those in high CTL Immune-Active Class. Multiomics comprising lncRNA score, PD-L1 expression and TMB could accurately predict immunotherapy efficacy.

Legal entity responsible for the study

Herui Yao.

Funding

Grants from the National Natural Science Foundation of China (81372819, 81572596, U1601223), the Natural Science Foundation of Guangdong Province (2017A030313828), the Guangzhou Science and Technology Program (201704020131), the Sun Yat-Sen University Clinical Research 5010 Program (2018007).

Disclosure

All authors have declared no conflicts of interest.

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Mini Oral session 2 Mini Oral session

94O - Safety and antitumor activity of sitravatinib in combination with tislelizumab in patients with advanced solid tumors: Ovarian cancer cohort data

Presentation Number
94O
Lecture Time
08:15 - 08:20
Speakers
  • B. Gao (Blacktown, Australia)
Session Name
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2019
Time
08:00 - 09:00
Authors
  • B. Gao (Blacktown, Australia)
  • J. Goh (South Brisbane QLD, ACT, Australia)
  • B. Markman (Victoria, ACT, Australia)
  • M. Voskoboynik (Melbourne, Australia)
  • H. Gan (Melbourne, ACT, Australia)
  • J. Coward (Brisbane, Australia)
  • D. Palmieri (Blacktown, Australia)
  • J. So (Melbourne, VIC, ACT, Australia)
  • T. Meniawy (Perth, WA, Australia)
  • C. Chen (Beijing, China)
  • X. Xiang (Beijing, China)
  • J. Qiu (Beijing, China)
  • Y. Xu (Shanghai, China)
  • L. Yang (Beijing, China)
  • M. Millward (Perth, WA, Australia)

Abstract

Background

Sitravatinib is an investigational, orally bioavailable, receptor tyrosine-kinase inhibitor with immune modulatory and potential antitumor activity. Tislelizumab is an investigational, humanized IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death receptor-1 (PD-1). We assessed the safety and antitumor activity of sitravatinib plus tislelizumab in patients with advanced solid tumors.

Methods

This is an open-label, multicenter, non-randomized, phase Ib study (NCT03666143). This cohort evaluated anti-PD-(L)1 antibody-naive patients with recurrent, platinum-resistant, epithelial ovarian cancer who were treated with 120 mg of sitravatinib once daily in combination with 200 mg tislelizumab every 3 weeks until disease progression, unacceptable toxicity, death, withdrawal of consent, or study termination. The primary objective was to assess the safety and tolerability of this combination therapy. Overall response rate, duration of response (DOR), disease control rate, and progression-free survival (PFS) were assessed as secondary endpoints.

Results

As of 17 July 2019, 20 patients (median age, 66.0 years) were enrolled; median number of prior regimens was 5 (range, 2–12). All 20 patients received study drugs and were included in the safety analysis. Common (frequency ≥10%) grade ≥3 treatment-emergent adverse events (TEAEs) assessed as related to sitravatinib by investigators were hypertension (25%) and fatigue (10%). Six patients had AEs that led to sitravatinib discontinuation. The common (frequency ≥10%) grade ≥3 TEAE assessed as related to tislelizumab by investigators was increased transaminases (10%). Three patients had AEs that led to tislelizumab discontinuation. Of 17 efficacy-evaluable patients, 4 achieved confirmed partial response, 11 had stable disease, and 2 had progressive disease per RECIST version 1.1. Median PFS was 18.0 weeks; median DOR was not reached (NR) (both ranges, 12.29 weeks–NR).

Conclusion

Combination treatment with sitravatinib and tislelizumab was manageable and showed promising antitumor activity in patients with ovarian cancer.

Clinical trial identification

NCT03666143.

Editorial acknowledgement

Writing assistance was provided by Ira Mills, PhD, of Ashfield Healthcare Communications.

Legal entity responsible for the study

BeiGene.

Funding

BeiGene.

Disclosure

B. Gao: Advisory / Consultancy: Merck Sharp & Dohme. J. Goh: Advisory / Consultancy: Bristol-Myers Squibb, AstraZeneca, and Ipsen; Honoraria (self), Payment for speaking engagements: Merck Sharp & Dohme. B. Markman: Advisory / Consultancy: Novartis. M. Voskoboynik: Honoraria (self): AstraZeneca and MSD Oncology; Travel / Accommodation / Expenses: Bristol-Myers Squibb. H.K. Gan: Advisory / Consultancy: AbbVie, Bristol-Myers Squibb, and Merck Sharp & Dohme; Speaker Bureau / Expert testimony: Eisai and Merck Serono; Research grant / Funding (self): AbbVie. J. Coward: Advisory / Consultancy: Takeda and Merck Sharp & Dohme; Research grant / Funding (self): AstraZeneca. C. Chen: Shareholder / Stockholder / Stock options, Full / Part-time employment: BeiGene. X. Xiang: Shareholder / Stockholder / Stock options, Full / Part-time employment: BeiGene. J. Qiu: Shareholder / Stockholder / Stock options, Full / Part-time employment: BeiGene. Y. Xu: Shareholder / Stockholder / Stock options, Full / Part-time employment: BeiGene. L. Yang: Shareholder / Stockholder / Stock options, Full / Part-time employment: BeiGene. M. Millward: Advisory / Consultancy: Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, and AstraZeneca. All other authors have declared no conflicts of interest.

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Mini Oral session 2 Mini Oral session

95O - The immunoglobulin superfamily receptome defines cancer-relevant networks associated with response to immunotherapy

Presentation Number
95O
Lecture Time
08:20 - 08:25
Speakers
  • N. Martinez-Martin (South San Francisco, United States of America)
Session Name
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2019
Time
08:00 - 09:00
Authors
  • N. Martinez-Martin (South San Francisco, United States of America)
  • E. Verschueren (South San Francisco, United States of America)
  • B. Husain (South San Francisco, AL, United States of America)

Abstract

Background

Cell surface receptors fundamentally determine physiological and pathological signaling, and as such, deciphering the ensemble of receptor-ligand interactions in the extracellular milieu is vital to understand cellular communication and identify new therapeutic targets. Despite its clinical relevance, the Immunoglobulin Superfamily (IgSF) remains remarkably uncharacterized and many proteins, including some immune checkpoints, are orphan. In this study, we present the first experimentally validated map of receptor-ligand interactions, the IgSF Interactome.

Methods

An automated platform for unbiased and high sensitivity receptor discovery was implemented. Using this technology, we interrogate 445 IgSF proteins for binding to most single transmembrane receptors in the human genome.

Results

The IgSF Interactome consists of over 500 interactions, with 85% previously unreported. Using orthogonal methodologies, we confirm loss-of-binding mutations specifically found in tumors, as well as new potential modulators for immune checkpoints such as PD-L1/PD-L2. Integration of this map of extracellular interactions with gene expression profiles in tumors and healthy tissues reveals receptor-ligand networks dysregulated in cancer. Furthermore, investigation of the IgSF Interactome in a large cohort of patients with metastatic urothelial cancer who were treated with the anti-PD-L1 agent Atezolizumab identifies interacting protein signatures associated with clinical outcome, suggesting new determinants of response to treatment.

Conclusion

The IgSF Interactome represents the first map of receptor-ligand interactions in humans, providing a framework for understanding the functional organization of the surfaceome during homeostasis and disease, and ultimately informing therapeutic development.

Legal entity responsible for the study

Genentech, Inc.

Funding

Genentech, Inc.

Disclosure

N. Martinez-Martin: Shareholder / Stockholder / Stock options: Roche. E. Verschueren: Shareholder / Stockholder / Stock options: Roche. B. Husain: Shareholder / Stockholder / Stock options: Roche.

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Mini Oral session 2 Mini Oral session

Discussion led by Moderators

Lecture Time
08:25 - 09:00
Speakers
  • P. Romero (Epalinges, Switzerland)
  • M. Donia (Herlev, Denmark)
Session Name
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2019
Time
08:00 - 09:00
Authors
  • P. Romero (Epalinges, Switzerland)
  • M. Donia (Herlev, Denmark)