Abstract 1209P
Background
This multicenter, phase II study aims to evaluate the safety and efficacy of regorafenib + nivolumab in multiple cohorts of patients (pts) with advanced solid tumors. We report interim results from the ESCC cohort.
Methods
Pts aged ≥18 years with ECOG PS 0/1 were treated with 480 mg intravenous nivolumab on Day 1 and 90 mg/day regorafenib orally on day 1–21 of each 28-day cycle. If tolerated, the regorafenib dose could be escalated to 120 mg/day from cycle 2. The primary endpoint was objective response rate (ORR; RECIST v1.1). Secondary endpoints included progression-free survival, overall survival, and safety (CTCAE v5.0). An exploratory analysis of response according to PD-L1 status was performed.
Results
37 pts with pre-treated ESCC were enrolled and 30 treated; 21 pts (70%) were receiving treatment at data cut-off (March 3, 2022). Median age was 62 years, 90% of pts were male, 70% were from Asia, 53% had ECOG PS 1, and 67% had received 1 prior therapy. ORR was 43%; 3 pts (10%) had confirmed complete response and 10 (33%) confirmed partial response (Table). Clinical responses were observed in both PD-L1-positive pts (ORR 83% [n=5/6] tumor proportion score [TPS] ≥1%) and PD-L1-negative pts (ORR 36% [n=4/11] TPS <1%). 28 pts had drug-related treatment-emergent adverse events (TEAEs): 13 (43%) were grade 3 and no pt had grade 4/5. Most common any-grade drug-related TEAEs were hand–foot skin reaction (70%), skin rash (33%), and decreased appetite (27%). Drug-related TEAEs led to discontinuation of nivolumab in 3 pts (10%) and regorafenib in 1 pt (3%). At data cut-off, median number of nivolumab infusions was 6 (range 1–12) and the median regorafenib treatment duration was 24 weeks (range 3–44). Table: 1209P
| Outcome | N=30* |
| Objective response rate, n (%) | 13 (43) |
| Complete response | 3 (10) |
| Partial response | 10 (33) |
| Stable disease, n (%) | 9 (30) |
| Disease control rate, n (%) | 22 (73) |
| Progressive disease, n (%) | 7 (23) |
| Median PFS, months (80% CI) | 6.9 (3.6, not estimable) |
Conclusions
Preliminary data for the regorafenib and nivolumab combination showed promising efficacy in pts with pre-treated ESCC, regardless of PD-L1 expression, and acceptable safety.
Clinical trial identification
NCT04704154.
Editorial acknowledgement
Editorial assistance provided by Matthew Reynolds of OPEN Health Communications, London, UK, with financial support from Bayer.
Legal entity responsible for the study
Bayer Bristol Myers-Squibb Ono Pharmaceuticals Co., Ltd.
Funding
Bayer, Bristol Myers-Squibb, Ono Pharmaceutical Co., Ltd.
Disclosure
L. Bai: Financial Interests, Personal, Invited Speaker: Pfizer, TTY Biopharm, Ono, Bristol Myers-Squibb, MSD, Ely Lilly, Novartis; Financial Interests, Personal, Research Grant: Eisai. C. Chiu: Financial Interests, Personal, Invited Speaker: MSD, ACT Genomics; Financial Interests, Institutional, Research Grant: Cstone, Abbvie, MSD, AstraZeneca, Roche. S. Kadowaki: Financial Interests, Personal, Speaker’s Bureau: Taiho, Eli Lilly, MSD, Ono, Daiichi Sankyo, Bristol Myers-Squibb, Bayer, Merck Serono, Eisai; Financial Interests, Institutional, Research Grant: Taiho, Eli Lilly, MSD, Ono, Daiichi Sankyo, Chugai, Nobelpharma, Yansen. M. Robert: Financial Interests, Institutional, Advisory Role: Novartis, Eisai, Novartis; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Travel grant: Merck, Novartis. H. Hara: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, Boehringer Ingelheim, Dainippon Sumitomo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, MSD, Ono, Bayer, Chugai, Kyowa Hakko Kirin, Lilly, Merck Biopharma, Sanofi, Taiho, Takeda, Yakult; Financial Interests, Institutional, Invited Speaker: Amgen, Astellas, AstraZeneca, Bayel, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Merck Biopharma, MSD, Ono, Taiho. F. Bergamo: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Other, Accomodation, travel for congress: Bayer; Financial Interests, Personal, Invited Speaker, Accomodation, travel for congress: Ipsen. S. Pernot: Financial Interests, Personal, Speaker’s Bureau: Amgen, Merck, Bristol Myers-Squibb, Servier, Pierre Fabre, AstraZeneca. D. Cunningham: Financial Interests, Institutional, Advisory Board: OVIBIO ; Financial Interests, Institutional, Research Grant: MedImmune, AstraZeneca, Clovis, Eli Lilly, 4SC, Bayer, Celgene, Roche. B. Keam: Financial Interests, Personal, Advisory Board: CbsBioscience, Cellid, Handok, ImmunOncia, Merck, NeoImmunetech, TrialInformatics,; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, MSD Oncology, Ono Pharmaceutical,. Y. Matsumura: Financial Interests, Personal, Full or part-time Employment: Ono Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Ono Pharmaceuticals. K. Enya: Financial Interests, Personal, Full or part-time Employment: Ono Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Ono Pharmaceuticals. I. Waxman: Financial Interests, Personal, Full or part-time Employment: Bristol-Myers Squibb. L. Jin: Financial Interests, Personal, Full or part-time Employment: Bristol-Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb. D. Ngo: Financial Interests, Personal, Full or part-time Employment: Bayer; Financial Interests, Personal, Stocks/Shares: Bayer. U. Drews: Financial Interests, Personal, Full or part-time Employment: Bayer; Financial Interests, Personal, Stocks/Shares: Bayer. C. Mancao: Financial Interests, Personal, Full or part-time Employment: Bayer. M. Le Berre: Financial Interests, Personal, Full or part-time Employment: Bayer. K. Kato: Financial Interests, Personal, Advisory Role: Ono Pharmaceuticals, Bristol Myers Squibb, Bayer, AstraZeneca, Beigene, Taiho, Merck Biopharma, Amgen, Novartis, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceuticals, Bristol-Myers Squibb, Merck & Co.; Financial Interests, Institutional, Research Grant: Ono Pharmaceuticals, Bristol Myers Squibb, Merck & Co., Bayer, AstraZeneca, Beigene, Taiho, Oncolys Biopharma, Janssen Pharmaceutical. All other authors have declared no conflicts of interest.