Abstract 1481
Background
Local tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with checkpoint inhibition augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ipilimumab (ipi) +/- nivolumab (nivo) was not only safe in patients (pts) with operable, early stage breast cancer (ESBC) but also generated robust intra-tumoral and systemic immune responses. In this randomized phase 2 study, we evaluate the disease specific impact of peri-op ipi/nivo/cryo versus standard care in women with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC), a subset at high risk of early relapse (NCT03546686).
Trial design
Eligible pts are ≥18y, with ER < 10%, PR < 10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. Approximately 160 pts will be randomized to one of two arms: definitive breast surgery (control arm) or ipi/nivo/cryo followed by breast surgery and adjuvant nivo (intervention arm). Pts in the intervention arm will undergo percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and will receive ipi (1mg/kg IV) with nivo (240mg IV) 1 to 5 days prior to cryo. After surgery, pts in the intervention arm will receive 3 additional doses of nivo at 240mg IV Q2 weeks. Adjuvant capecitabine is recommended for all study patients per local standard-of-care. Patients will be stratified by NAC platinum administration, NAC anthracycline administration, and clinical nodal status at study entry (positive versus negative). The primary endpoint is 3-year event free survival (EFS). Secondary endpoints include invasive disease-free survival (iDFS), distant disease-free survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore potential predictors of efficacy and toxicity.
Clinical trial identification
NCT03546686.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Susan G. Komen, Bristol-Meyers Squibb, BTG International Ltd., Breast Cancer Research Foundation, ASCO Advanced Clinical Research Award.
Disclosure
H.L. McArthur: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Spectrum Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Immunomedics; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Genomic Health; Research grant / Funding (institution): ZIOPHARM Oncology; Travel / Accommodation / Expenses: Puma Biotechnology. E.A. Comen: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Genentech; Advisory / Consultancy: Novartis; Advisory / Consultancy: Henron Therapeutics. S.B. Solomon: Advisory / Consultancy: BTG; Advisory / Consultancy: Johnson & Johnson; Advisory / Consultancy: Adgero; Advisory / Consultancy: Aperture Medical; Advisory / Consultancy: Xact Robotics; Advisory / Consultancy: Innoblative Designs; Shareholder / Stockholder / Stock options: Immunomedics; Shareholder / Stockholder / Stock options: Aspire Bariatrics; Shareholder / Stockholder / Stock options: Aperture Medical; Shareholder / Stockholder / Stock options: Johnson & Johnson; Shareholder / Stockholder / Stock options: Motus GI; Shareholder / Stockholder / Stock options: Progenics; Research grant / Funding (institution): Johnson & Johnson; Research grant / Funding (institution): Elesta; Research grant / Funding (institution): AngioDynamics; Research grant / Funding (institution): GE Healthcare. J.H.S. Leal: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche/Genentech; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca. D.B. Page: Honoraria (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Merck Sharpe & Dohme; Advisory / Consultancy: Syndax; Advisory / Consultancy: Nektar; Advisory / Consultancy: Nanostring Technologies; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Puma Biotechnology; Speaker Bureau / Expert testimony: Genentech/Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: MedImmune; Speaker Bureau / Expert testimony: Philips Healthcare. All other authors have declared no conflicts of interest.
Resources from the same session
2670 - Molecular subtypes of metastatic(met) gastric cancer(GC) (MoTriGastric): new biomarkers closer to the clinics
Presenter: Maria Alsina Maqueda
Session: Poster Display session 2
Resources:
Abstract
3797 - Exploring candidate signal transduction pathways for targeted therapy in esophageal cancer
Presenter: Aafke Creemers
Session: Poster Display session 2
Resources:
Abstract
5485 - Clinical implication of CLDN18, RhoGAP, and E-cadherin in gastric signet ring cell carcinoma
Presenter: Hyunho Kim
Session: Poster Display session 2
Resources:
Abstract
1970 - Identification of a spectrum of germline mutations for hereditary diffuse gastric cancer in the Russian population by next-generation sequencing.
Presenter: IRINA EFIMOVA
Session: Poster Display session 2
Resources:
Abstract
4989 - The molecular profiling and prognostic value of Chinese gastric signet ring cell carcinoma patients
Presenter: Jia Wei
Session: Poster Display session 2
Resources:
Abstract
7145 - A phase 2 basket study of MCLA-128, a bispecific antibody targeting the HER3 pathway, in NRG1 fusion-positive advanced solid tumors
Presenter: Alison Schram
Session: Poster Display session 2
Resources:
Abstract
1406 - Simultaneous Resection of Pancreatic Cancer and Liver Oligometastases After Induction Chemotherapy in Stage IV Patients:an Open-Label Prospective Randomized Multicenter phase 3 trial(CSPAC-1)
Presenter: Miaoyan Wei
Session: Poster Display session 2
Resources:
Abstract
1530 - Multicenter randomized phase II trial of 5-Fluorouracil/leucovorin (5-FU/LV) with or without liposomal irinotecan (nal-IRI) in metastatic biliary tract cancer (BTC) as second-line therapy after progression on gemcitabine plus cisplatin (GemCis): NIFTY trial
Presenter: Changhoon Yoo
Session: Poster Display session 2
Resources:
Abstract
1563 - A randomized phase II study of Maintenance therapy with multiepitope vaccine Tedopi (OSE2101) ± nivolumab or FOLFIRI after induction chemotherapy (CT) with FOLFIRINOX in patients (Pts) with advanced Pancreatic ductal adenocarcinoma (aPDAC) (TEDOPaM – PRODIGE 63 GERCOR study)
Presenter: Cindy Neuzillet
Session: Poster Display session 2
Resources:
Abstract
2780 - A phase 3, randomized, double-blind, placebo-controlled, international study of durvalumab in combination with gemcitabine plus cisplatin for patients with advanced biliary tract cancers: TOPAZ-1
Presenter: Do-Youn Oh
Session: Poster Display session 2
Resources:
Abstract