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
4596 - A Phase 2, Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-Mutant Melanoma Brain Metastasis (MBM) (POLARIS)
Presenter: Michael Davies
Session: Poster Display session 3
Resources:
Abstract
1891 - Continuation of annual screening mammograms and breast-cancer mortality in women over 70
Presenter: Xabier Garcia De Albeniz
Session: Poster Display session 3
Resources:
Abstract
5587 - Introducing standardized medical procedure and dynamic decision support program in precision oncology for the community of practice
Presenter: Istvan Petak
Session: Poster Display session 3
Resources:
Abstract
4757 - Effectively using primary care givers in oncology care through capacity building, task sharing and techno-mentoring.
Presenter: Dinesh Pendharkar
Session: Poster Display session 3
Resources:
Abstract
4497 - A single institution review of capecitabine related acute admissions and cost analysis
Presenter: Gemma Dart
Session: Poster Display session 3
Resources:
Abstract
2187 - Health status of middle-aged and older cancer survivors in China: results from the China Health and Retirement Longitudinal Study (CHARLS)
Presenter: Jiarui Li
Session: Poster Display session 3
Resources:
Abstract
5101 - Crossed looks on lung cancer perception and knowledge from general public and physicians in France: results of a two-fold survey
Presenter: Céline Mascaux
Session: Poster Display session 3
Resources:
Abstract
4354 - Knowledge and perception of clinical trials (CTs) and attitude towards participation among Polish oncological patients - A pilot survey
Presenter: Artur Kotowski
Session: Poster Display session 3
Resources:
Abstract
3499 - Achieving best possible cancer treatment outcomes in care pathways through benchmarking; ABC-Benchmarking
Presenter: Anke Wind
Session: Poster Display session 3
Resources:
Abstract
2270 - Impact of 10-day Fulbright Specialist Program (FSP) and Project Pink Blue (PPB) Education Sessions on Medical Oncology knowledge among Doctors that treat cancer in Nigeria
Presenter: Mike Martin
Session: Poster Display session 3
Resources:
Abstract