Abstract 1285
Background
Anaphylatoxin C5a is released in the cancer microenvironment and binds to the C5aR receptor, which in turns promotes protumoral inflammation and immune suppression through recruitment and activation of myeloid derived suppressor cells (MDSC) and neutrophils. Overexpression of C5aR has been reported in several tumor types and correlates with aggressive tumor features and poor prognosis. Additionally, C5aR was found to be upregulated in NSCLC patients in progression after an initial response to an anti-PD-(L)1 therapy (aPD1). IPH5401, a fully human anti-C5aR1 antibody, inhibits the C5a mediated effects on MDSC and neutrophils. Preclinical data suggest that the combined blockade of C5aR1 and aPD1 synergistically reduce tumor growth and delay tumor progression. These data suggest that combining IPH5401 with aPD1 may improve efficacy and overcome secondary resistance to aPD1.
Methods
This is an ongoing phase I to evaluate the safety of IPH5401 + durvalumab (durva) in advanced solid tumors. In the 3 + 3 dose-escalation, patients (pts) receive IPH5401 at 4 dose levels (DL) (DL1, DL2, DL3 [Q1w] and DL4 [Q2w]) single agent during the first 2 weeks (w) then in combination with durva 1500 mg Q4w. Blood samples are collected at various time points for characterization of pharmacokinetics, pharmacodynamics and immunogenicity. Upon completion of the phase I part and determination of a recommended phase II dose, expansion cohorts in NSCLC and HCC will be activated.
Results
As of April, 30th 2019, 12 pts have been enrolled (4 HCC, 2 UCC, 5 NSCLC, 1 RCC). No DLT was seen to date. DL3 and DL4 are ongoing. A total of 11 treatment related AEs (TRAEs) were reported in 5 patients: G2 diarrhea with lymphocytic colitis (n = 1), G1 diarrhea (n = 1), G1 skin rashes (n = 2), G1 White blood cell decrease (n = 1), G1 pneumopathy (n = 1), G1 lung disorder (n = 1), G1 fatigue (n = 1), G1 arthralgia (n = 1), G1 back pain (n = 1), G1 musculoskeletal chest pain (n = 1). There were no grade 3/4 TRAEs and no TRAEs that led to study discontinuation.
Conclusions
Preliminary results of this combination of IPH5401 plus durva suggest a manageable toxicity profile. Results of dose escalation including PK/PD data will be presented.
Clinical trial identification
NCT03665129.
Editorial acknowledgement
Legal entity responsible for the study
Innate Pharma.
Funding
Innate Pharma and AstraZeneca.
Disclosure
C. Massard: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Beigene; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Debiopharm; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Orion. P. Cassier: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Research grant / Funding (institution): Blueprint Medicines; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Toray; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Innate Pharma; Research grant / Funding (institution): Janssen. J.C. Bendell: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Gilead; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution): Five Prime; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution), Travel / Accommodation / Expenses: MedImmune; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Taiho; Advisory / Consultancy, Research grant / Funding (institution): MacroGenics; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: OncoMed; Advisory / Consultancy, Research grant / Funding (institution): LEAP; Research grant / Funding (institution): TG Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Innate Pharma; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BI; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo. D.B. Marie: Shareholder / Stockholder / Stock options, Full / Part-time employment: Innate Pharma. M. Blery: Shareholder / Stockholder / Stock options, Full / Part-time employment: Innate Pharma. C. Morehouse: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Ascierto: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Zerbib: Shareholder / Stockholder / Stock options, Full / Part-time employment: Innate Pharma. E. Mitry: Shareholder / Stockholder / Stock options, Full / Part-time employment: Innate Pharma. A.W. Tolcher: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AbbVie; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: ADC Therapeutics; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Adagene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Agenus; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AroBioTX; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ascentage; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Aximmune; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BioInvent; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Birdie; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boston Bio; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: EMD Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Forbius; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: HBM partners; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ignitia; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Immunome; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Immunomet; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Jazz; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Mekanistic; Research grant / Funding (institution): Innate Pharma.
Resources from the same session
4614 - Predictors of Response to Checkpoint Inhibitors in Naïve and Ipilimumab-Refractory Melanoma
Presenter: Domenico Mallardo
Session: Poster Display session 3
Resources:
Abstract
2901 - IFN-γ/IL-10 ratio as predictive biomarker for response to anti-PD-1 therapy in metastatic melanoma patients
Presenter: Emilio Giunta
Session: Poster Display session 3
Resources:
Abstract
2306 - Multiplex Chromogenic Immunohistochemistry (IHC) for Spatial Analysis of Checkpoint-Positive Tumor Infiltrating Lymphocytes (TILs)
Presenter: Scott Ely
Session: Poster Display session 3
Resources:
Abstract
1678 - The role of PD-L1 expression as a predictive biomarker in advanced renal cell carcinoma: a meta-analysis of randomized clinical trials.
Presenter: Alberto Carretero-Gonzalez
Session: Poster Display session 3
Resources:
Abstract
5138 - Radiomic Features as a Non-invasive Biomarker to Predict Response to Immunotherapy in Recurrent or Metastatic Urothelial Carcinoma
Presenter: Kye Jin Park
Session: Poster Display session 3
Resources:
Abstract
5800 - Integrative combination of high-plex digital profiling techniques and cluster analysis to reveal complex immune biology in the tumor microenvironment of mesothelioma
Presenter: Carmen Ballesteros-Merino
Session: Poster Display session 3
Resources:
Abstract
5736 - Predictive factors of response to immunotherapy in 198 patients with metastatic non-microcytic lung cancer (mNSCLC): real world data from 2 university hospitals in Spain
Presenter: Juan Felipe Cordoba Ortega
Session: Poster Display session 3
Resources:
Abstract
5645 - Evaluating Lung CT Density Changes Among Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) Treated with Thoracic Radiotherapy (TRT) alone or TRT Followed by Combined Ipilimumab (IPI) and Nivolumab (NIVO).
Presenter: Kujtim Latifi
Session: Poster Display session 3
Resources:
Abstract
1540 - Immuno-oncology therapy biomarkers differences between polyoma-virus positive and negative Merkel cell carcinomas
Presenter: Zoran Gatalica
Session: Poster Display session 3
Resources:
Abstract
4538 - Can we improve patient selection for phase 1 clinical trials (Ph1) based on Immuno-Oncology score prognostic index (VIO)?
Presenter: Ignacio Matos Garcia
Session: Poster Display session 3
Resources:
Abstract