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
4634 - Comparative molecular analyses between microsatellite stable BRAFV600E mutant colorectal cancers and BRAFV600E mutant melanomas.
Presenter: Mohamed Salem
Session: Poster Display session 3
Resources:
Abstract
3264 - A novel preclinical model of RAF-independent MEK1 mutant tumors and its treatment with novel ATP competitive MEK inhibitor
Presenter: Luca Hegedus
Session: Poster Display session 3
Resources:
Abstract
4918 - HER2 inhibition in Aggressive Squamous Cell Carcinomas driven by a common MET Sema Domain Polymorphism
Presenter: Nur Afiqah Mohamed Salleh
Session: Poster Display session 3
Resources:
Abstract
2426 - ADAM9 as a target for lung cancer treatment
Presenter: Yuh-pyng Sher
Session: Poster Display session 3
Resources:
Abstract
5537 - Novel polyurea/polyurethane nanocapsules loaded with a tambjamine analog to improve cancer chemotherapy delivery and safety in lung cancer
Presenter: Marta Perez Hernandez
Session: Poster Display session 3
Resources:
Abstract
1597 - Discovery of Clinical Candidate DBPR112, a Furanopyrimidine-based Epidermal Growth Factor Receptor Inhibitor for the Treatment of Non-Small Cell Lung Cancer
Presenter: Hsing-pang Hsieh
Session: Poster Display session 3
Resources:
Abstract
3543 - Molecular characteristics in lung squamous cell carcinomas dependent on TP53 status – putative targets
Presenter: Vilde Haakensen
Session: Poster Display session 3
Resources:
Abstract
4111 - Comparison of molecular profiles between primary tumour and matched metastasis in non-small cell lung cancer
Presenter: Asuka Kawachi
Session: Poster Display session 3
Resources:
Abstract
4559 - Treatment with BLU-667, a potent and selective RET inhibitor, provides rapid clearance of ctDNA in Patients with RET-altered Non-Small Cell Lung Cancer (NSCLC) and Thyroid Cancer
Presenter: Giuseppe Curigliano
Session: Poster Display session 3
Resources:
Abstract
2501 - Triple MET/SRC/PIM inhibition in MET addicted tumors
Presenter: Ilaria Attili
Session: Poster Display session 3
Resources:
Abstract