Abstract 1651P
Background
Some previous studies evaluated the efficacy of anitiangiogenic agents in ES-SCLC pts. This prospective single institutional phase I study aimed to determine the recommended dose (RD) of ramucirumab (RAM), anti-VEGF receptor-2 antibody, in combination with irinotecan (Iri) and cisplatin (Cis), and to perform an exploratory analysis of the efficacy and tolerability at RD in pts with ES-SCLC.
Methods
We recruited chemo-naïve ES-SCLC pts who were fit for RAM and prescribed Iri (6 mg/m2, day 1, 8 and 15)/ Cis (60 mg/m2, day 1) plus RAM (day 1 and 15) every 4 weeks up to 4 cycles, followed by maintenance therapy with RAM every 2 weeks. Dose-limiting toxicity (DLT) was assessed during the first cycle of treatment. The RD of RAM (either 10 mg/kg or 8 mg/kg) was determined by a traditional 3+3 design, and the total number of pts treated at RD was set at 10 for an exploratory analysis of the efficacy and tolerability.
Results
Between June 2018 and February 2020, 10 pts were enrolled in this study, with median age of 63 years (range 50-73), and 8 of them were male. The first 3 pts receiving Iri plus Cis with the dose of RAM at 10 mg/kg did not experience the DLT. Therefore, the RD of RAM was defined as 10 mg/kg. A total of 10 pts received Iri plus Cis with RAM at 10 mg/kg. All of them completed 4 cycles of combination therapy. 9 of them received maintenance therapy with RAM and median number of RAM doses was 6 (range 4-15). ORR was 100 % (95% CI, 69-100 %), with median PFS of 7.2 months (95% CI, 5.3-9.0 months), and median OS of 22.4 months (95% CI, 12.1 months-NR). PFS rate at 6 months was 70 % (95% CI, 33-89%), and OS rate at 12 and 18 months were 100 % and 59 % (95% CI, 19-85 %). Grade 3 or 4 febrile neutropenia, neutropenia, thrombocytopenia, and diarrhea were observed in 1, 4, 1 and 1 pts, respectively. With respect to toxicities related to RAM, grade 3 or higher bleeding or hemorrhage, pulmonary embolism, hypertension and proteinuria were observed in 0, 1, 2 and 0 pts, respectively. No treatment-related death was observed.
Conclusions
This phase I study showed good efficacy and tolerability of RAM at 10mg/kg in combination with Iri plus Cis in chemo-naïve patients with ES-SCLC.
Clinical trial identification
UMIN000032671.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Eli Lilly.
Disclosure
T. Takahashi: Financial Interests, Personal, Other, Honoraria: AstraZeneca KK; Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Eli Lilly Japan K.K.; Financial Interests, Personal, Other, Honoraria: MSD K.K.; Financial Interests, Personal, Other, Honoraria: Pfizer Japan Inc.; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim Japan; Financial Interests, Personal, Other, Honoraria: Roche Diagnostics K.K.; Financial Interests, Institutional, Funding: AstraZeneca KK; Financial Interests, Institutional, Funding: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: Eli Lilly Japan K.K.; Financial Interests, Institutional, Funding: Ono Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: MSD K.K.; Financial Interests, Institutional, Funding: Pfizer Japan Inc.; Financial Interests, Institutional, Funding: Boehringer Ingelheim Japan; Financial Interests, Institutional, Funding: Amgen Inc. N. Mamesaya: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim Japan; Financial Interests, Personal, Other, Honoraria: MSD K.K.; Financial Interests, Personal, Other, Honoraria: AstraZeneca KK; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: Boehringer Ingelheim Japan. H. Kobayashi: Financial Interests, Personal, Other, Honoraria: AstraZeneca KK; Financial Interests, Personal, Other, Honoraria: Eli Lilly Japan K.K.; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical Co. Ltd. S. Omori: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: Daiichi Sankyo Co. Ltd. K. Wakuda: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim Japan; Financial Interests, Personal, Other, Honoraria: Eli Lilly Japan K.K.; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: MSD K.K.; Financial Interests, Personal, Other, Honoraria: AstraZeneca KK; Financial Interests, Institutional, Funding: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: AstraZeneca KK; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: AbbVie. A. Ono: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: AstraZeneca KK. T. Naito: Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical Co. Ltd. H. Murakami: Financial Interests, Personal, Other, Honoraria: AstraZeneca KK; Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb Japan; Financial Interests, Personal, Other, Honoraria: MSD K.K.; Financial Interests, Personal, Other, Honoraria: Pfizer Japan Inc.; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Eli Lilly Japan K.K.; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Takeda Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: Takeda Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: AstraZeneca KK; Financial Interests, Institutional, Funding: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: Daiichi Sankyo Co. Ltd.; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Institutional, Funding: IQVIA. H. Kenmotsu: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim Japan; Financial Interests, Personal, Other, Honoraria: Eli Lilly Japan K.K.; Financial Interests, Personal, Other, Honoraria: Kyowa Hakko Kirin Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb Japan; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim Japan; Financial Interests, Personal, Other, Honoraria: MSD K.K.; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Other, Honoraria: AstraZeneca KK; Financial Interests, Personal, Other, Honoraria: Pfizer Japan Inc.; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Funding: AstraZeneca KK; Financial Interests, Institutional, Funding: Daiichi Sankyo Co. Ltd.; Financial Interests, Institutional, Funding: Novartis. All other authors have declared no conflicts of interest.