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Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.

Innate and adaptive immunotherapy: An orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T-cell therapy in patients with third line or greater TNBC.

Sub-category:
Triple-Negative

Category:
Breast Cancer—Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
e12566

Citation:
J Clin Oncol 37, 2019 (suppl; abstr e12566)

Author(s): Chaitali Singh Nangia, Mira Kistler, Leonard S. Sender, John H. Lee, Frank R. Jones, Omid Jafari, Patrick Soon-Shiong; Chan Soon Shiong Institute for Medicine, Laguna Hills, CA; Chan Soon Shiong Institute of Medicine, El Segundo, CA; Children's Hospital of Orange County, Laguna Hills, CA; Sanford Health, Sioux Falls, SD; Etubics Corporation, Seattle, WA; Medical Imaging Center of Southern California, Santa Monica, CA; Nantkwest, Culver City, CA

Abstract Disclosures

Abstract:

Background: Triple-negative breast cancer (TNBC) is a heterogenous subtype of breast cancer that is frequently aggressive and has limited treatment options. We hypothesize that effective and sustained response against TNBC requires a coordinated approach that: 1. reverses the immune-suppressive tumor microenvironment, 2. induces immunogenic tumor cell death and 3. reengages NK and T-cell tumor response against a 4. cascade of tumor antigens. To test this hypothesis, we have developed a temporospatial approach that combines metronomic low dose chemotherapy, SBRT, off-the-shelf cryopreserved allogeneic NK cells, yeast and adenoviral tumor-associated antigen vaccines, an IL-15RαFc superagonist, and checkpoint inhibition. Methods: A phase 1b trial in patients with previously-treated metastatic TNBC was initiated. Treatment occurred in 3-week cycles of low-dose chemotherapy (aldoxorubicin, cyclophosphamide, cisplatin, nab-paclitaxel, 5-FU/L), antiangiogenic therapy (bevacizumab), SBRT, engineered allogeneic CD16 NK-92 cells (haNK), IL-15RαFc (N-803), adenoviral vector-based CEA, MUC1, brachyury, and HER2 vaccines, yeast vector-based Ras, brachyury and CEA vaccines, and an IgG1 PD-L1 inhibitor, avelumab. The primary endpoint is incidence of treatment-related adverse events (TRAEs). Secondary endpoints include ORR, DCR, PFS, and OS. Results: 8 subjects with 3rd-line or greater TNBC have received at least 3 treatment cycles (mean = 6 cycles). All treatment was administered in an outpatient setting. All subjects had at least 1 grade ≥3 TRAE, primarily chemotherapy-related neutropenia. Grade ≥3 haNK-related AEs (fever and fatigue) were observed in 2 subjects. 2 subjects experienced SAEs. 7 subjects remain alive, with 6 subjects receiving ongoing study treatment. 1 CR (confirmed) and 2 PRs (one confirmed) have been observed to date. Conclusions: These preliminary data suggest that low-dose chemo-radiation combined with innate and adaptive immunotherapy can be administered safely in an outpatient setting with a manageable safety profile. Clinical trial information: NCT03387085

 
Other Abstracts in this Sub-Category:

 

1. IMpassion130: updated overall survival (OS) from a global, randomized, double-blind, placebo-controlled, Phase III study of atezolizumab (atezo) + nab-paclitaxel (nP) in previously untreated locally advanced or metastatic triple-negative breast cancer (mTNBC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 1003 First Author: Peter Schmid
Category: Breast Cancer—Metastatic - Triple-Negative

 

2. Phase II COLET study: Atezolizumab (A) + cobimetinib (C) + paclitaxel (P)/nab-paclitaxel (nP) as first-line (1L) treatment (tx) for patients (pts) with locally advanced or metastatic triple-negative breast cancer (mTNBC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 1013 First Author: Adam Brufsky
Category: Breast Cancer—Metastatic - Triple-Negative

 

3. Pembrolizumab (pembro) with paclitaxel (taxol) or capecitabine (cape) as early treatment of metastatic triple-negative breast cancer (mTNBC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 1015 First Author: David B. Page
Category: Breast Cancer—Metastatic - Triple-Negative

 

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