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Attend this session at the
2019 ASCO Annual Meeting!


Session: Developmental Immunotherapy and Tumor Immunobiology

Type: Poster Session

Time: Saturday June 1, 8:00 AM to 11:00 AM

Location: Hall A


Session: Developmental Immunotherapy and Tumor Immunobiology

Type: Poster Discussion Session

Time: Saturday June 1, 1:15 PM to 2:45 PM

Location: Hall D1

Regorafenib plus nivolumab in patients with advanced gastric (GC) or colorectal cancer (CRC): An open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO, EPOC1603).

Sub-category:
Immune Checkpoint Inhibitors

Category:
Developmental Immunotherapy and Tumor Immunobiology

Meeting:
2019 ASCO Annual Meeting

Abstract No:
2522

Poster Board Number:
Poster Discussion Session (Board #166)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 2522)

Author(s): Shota Fukuoka, Hiroki Hara, Naoki Takahashi, Takashi Kojima, Akihito Kawazoe, Masako Asayama, Takako Yoshii, Daisuke Kotani, Hitomi Tamura, Yuichi Mikamoto, Ayako Sugama, Masashi Wakabayashi, Shogo Nomura, Akihiro Sato, Yosuke Togashi, Hiroyoshi Nishikawa, Kohei Shitara; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan; National Cancer Center Hospital East, Kashiwa, Japan; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan; Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan; Clinical Research Support Office, National Cancer Center Hospital East, Japan, Kashiwa, Japan; Division of Cancer Immunology, National Cancer Center, Kashiwa, Japan; National Cancer Center, Kashiwa, Japan; Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan

Abstract Disclosures

Abstract:

Background: Immune suppressive cells such as regulatory T cells (Tregs) or tumor-associated macrophages (TAMs) may contribute to resistance to anti-PD-1/PD-L1 inhibitors (A-PD1). Regorafenib, a potent inhibitor of angiogenic and oncogenic kinases, reduced TAMs in tumor models. The combination of regorafenib plus A-PD1 exhibited superior tumor growth suppression compared to either treatment alone in murine models. Methods: In this study, we enrolled patients (pts) with previously treated, advanced GC or CRC. The pts received regorafenib plus nivolumab in a dose-finding phase to estimate the maximum tolerated dose (MTD). Additional pts were enrolled in a dose-expansion phase to further establish the safety and determine the preliminary efficacy. Regorafenib of 80 to 160 mg was administered once daily for 21 on 7 days off with intravenous nivolumab 3 mg/kg every 2 weeks. The primary endpoint was dose-limiting toxicity (DLT) during cycle one (4 weeks) to estimate the MTD and the recommended dose. Results: Fifty pts were enrolled (25 GC; 25 CRC) until October 2018. The median prior treatment line was 3 (range 2-8). During dose-escalation, 3 DLTs were observed with regorafenib 160 mg, including grade (G) 3 maculopapular rash, mucositis and proteinuria, while there was no DLT with 80 or 120 mg. In the dose expansion cohort with regorafenib 120 mg, the dose was reduced to 80 mg owing to frequent G3 skin toxicities. Grade ≥ 3 treatment related adverse events occurred in 17 pts; the common events ( > 5%) being rash (14%), palmar-plantar erythrodysesthesia (10%), and proteinuria (8%). Objective tumor response was observed in 19 pts (38%) including 11 MSS GC, 7 MSS CRC and 1 MSI-H CRC for response rates of 44% in GC and 29% in MSS CRC. Three of the 7 A-PD1 pretreated GC pts achieved a partial response. The pre- and post-treatment tumor samples showed a reduction of FoxP3hiCD45RA-Tregs fraction at the tumor response. Conclusions: The combination of regorafenib 80mg plus nivolumab had a manageable safety profiles and encouraging anti-tumor activity in MSS GC and CRC pts, which warrants further investigations in a larger cohort. Updated biomarker analysis will be presented. Clinical trial information: NCT03406871

 
Other Abstracts in this Sub-Category:

 

1. Biomarker analyses from JAVELIN Renal 101: Avelumab + axitinib (A+Ax) versus sunitinib (S) in advanced renal cell carcinoma (aRCC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 101 First Author: Toni K. Choueiri
Category: Developmental Immunotherapy and Tumor Immunobiology - Immune Checkpoint Inhibitors

 

2. Phase I study of pembrolizumab in people with HIV and cancer.

Meeting: 2019 ASCO Annual Meeting Abstract No: 2500 First Author: Thomas S. Uldrick
Category: Developmental Immunotherapy and Tumor Immunobiology - Immune Checkpoint Inhibitors

 

3. Phase II study of durvalumab (MEDI4736) in cancer patients HIV-1-infected.

Meeting: 2019 ASCO Annual Meeting Abstract No: 2501 First Author: María González-Cao
Category: Developmental Immunotherapy and Tumor Immunobiology - Immune Checkpoint Inhibitors

 

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