Abstract 4874
Background
TNBC is an aggressive subtype with limited treatment options. We hypothesize that effective response against TNBC requires a coordinated approach that orchestrates both the innate and adaptive immune system. We further hypothesize that by orchestrating the activation of the entire immune system, we could accomplish immunogenic cell death with durable responses in this disease. We describe a first-in-human novel combination immunotherapy protocol of chemoradiation, cytokine-induced NK and T cell activation, checkpoint inhibition, and off-the-shelf high-affinity NK cell infusion.
Methods
We instituted this novel immunotherapy protocol consisting of low-dose metronomic chemoradiation therapy, combined with a novel IgG1 Fc-engineered IL-15-complexed protein (NabFc-N803), adenoviral and yeast tumor-associated antigen vaccines (MUC1, brachyury, CEA), a PD-L1 checkpoint inhibitor, and off-the-shelf high-affinity NK cells (haNK). A phase 1b trial in pts with metastatic TNBC was initiated in 9 pts, 8 of whom had relapsed after two or more lines of prior therapy (3rd-line). All pts received this combination therapy instituted over a three-week cycle as outpatients. Safety was assessed and efficacy confirmed by CT.
Results
Nine pts have been treated to date. All pts received at least 3 treatment cycles. 8 grade ≥3 treatment-related AEs were observed in 4 pts to date, of which 2 had haNK-related SAEs consisting of fever and fatigue. No pts experienced cytokine release syndrome. To date, early efficacy results are as follows: a disease control rate (CR+PR+SD) of 78% (7/9 pts); ORR (PR+CR) of 56% (5/9 pts). Two pts (22%; 2/9) achieved a complete response (CR). To date, 8 pts are alive, and the duration of response ranges from 2 mo to over 12 mo. 7 pts remain on study to date.
Conclusions
This first in human clinical trial of combination chemoradiation, cytokine fusion protein, checkpoint inhibitor, and NK cell therapy demonstrated a safe and tolerable immunotherapy protocol. Early efficacy data is encouraging with a 78% disease control rate, 56% ORR and 22% (2/9) CR in pts with metastatic TNBC, 2nd-line or greater.
Clinical trial identification
NCT03387085.
Editorial acknowledgement
Legal entity responsible for the study
NantKwest, Inc.
Funding
NantKwest, Inc.
Disclosure
P. Soon-Shiong: Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: NantCell; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: NantKwest; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: NantHealth; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: NantBio; Shareholder / Stockholder / Stock options: Celgene. S. Rabizadeh: Leadership role, Officer / Board of Directors: NantBio; Leadership role, Officer / Board of Directors: NantCell. J.H. Lee: Leadership role, Officer / Board of Directors: NantKwest; Leadership role, Officer / Board of Directors: NantCell. L. Sender: Leadership role, Officer / Board of Directors: NantKwest. F. Jones: Leadership role, Full / Part-time employment: NantCell; Leadership role, Officer / Board of Directors: Etubics. K. Niazi: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: NantBio. T. Seery: Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer. A. Rock: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: NantCell. All other authors have declared no conflicts of interest.
Resources from the same session
5887 - Factors of importance in procuring tumoroids from colorectal liver metastasis biopsies for precision medicine.
Presenter: Lars Henrik Jensen
Session: Poster Display session 2
Resources:
Abstract
2196 - FUSAFE individual patient data meta-analysis (MA) to assess the performance of dihydropyrimidine dehydrogenase (DPD) gene polymorphisms for predicting grade 4-5 fluoropyrimidine (FP) toxicity
Presenter: Marie-Christine Etienne-Grimaldi
Session: Poster Display session 2
Resources:
Abstract
2859 - Treatments (tx) after progression to first-line FOLFOXIRI + bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts): A pooled analysis of TRIBE and TRIBE-2 studies by GONO.
Presenter: Daniele Rossini
Session: Poster Display session 2
Resources:
Abstract
3888 - Randomized phase III study of sequential treatment with capecitabine or 5-fluorouracil (FP) plus bevacizumab (BEV) followed by the addition with oxaliplatin (OX) versus initial combination with OX+FP+ BEV in the first-line chemotherapy for metastatic colorectal cancer: The C-cubed study
Presenter: Takeshi Nagasaka
Session: Poster Display session 2
Resources:
Abstract
1065 - Early tumour shrinkage (ETS), depth of response (DpR) and associated survival outcomes in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC) classified according to Köhne prognostic category: retrospective analysis of the panitumumab (Pmab) PRIME study
Presenter: Andrea Sartore-Bianchi
Session: Poster Display session 2
Resources:
Abstract
1702 - Randomized phase II trial of CAPOX with planned oxaliplatin stop-and-go strategy as adjuvant chemotherapy after curative resection of colon cancer (CCOG-1302 study)
Presenter: Hiroyuki Yokoyama
Session: Poster Display session 2
Resources:
Abstract
5104 - A metabolomic recurrence score for risk-stratification of elderly patients (pts) with early colorectal cancer (eCRC)
Presenter: Samantha Di Donato
Session: Poster Display session 2
Resources:
Abstract
5285 - RAS mutant allele fraction in plasma predicts benefit to anti-angiogenic based first line treatment in metastatic colorectal cancer
Presenter: Giulia Martini
Session: Poster Display session 2
Resources:
Abstract
1790 - Impact of prophylactic systemic antibiotics (SA) on outcome of patients (pts) with RAS-wildtype (RAS-wt) metastatic colorectal carcinoma (mCRC) treated with cetuximab-based first-line therapy. Subgroup analysis of the german non-interventional study ERBITAG
Presenter: Stephan Sahm
Session: Poster Display session 2
Resources:
Abstract
3059 - Intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): A randomized, multicenter, prospective, phase III trial
Presenter: Rongxin Zhang
Session: Poster Display session 2
Resources:
Abstract