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Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer.

Horinouchi H, Yamamoto N, Fujiwara Y, Sekine I, Nokihara H, Kubota K, Kanda S, Yagishita S, Wakui H, Kitazono S, Mizugaki H, Tokudome T, Tamura T - Invest New Drugs (2015)

Bottom Line: The most common grade 3/4 adverse events (AEs) were decreased hemoglobin, leukopenia, and neutropenia.The safety profile was similar in both cohorts.The safety profile was consistent with the previously defined AE profile.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan, hhorinou@ncc.go.jp.

ABSTRACT

Background: Ipilimumab is an antibody that targets the cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor response. Adding ipilimumab 10 mg/kg to paclitaxel (PTX) and carboplatin (CBDCA) in a phased schedule improved progression-free survival in a phase II non-small-cell lung cancer (NSCLC) study.

Methods: This dose-escalating, phase I study was designed to identify the recommended dose of ipilimumab (3 or 10 mg/kg) by evaluating dose-limiting toxicity (DLT; Cycles 3 and 4) in phased combination with PTX (175 mg/m(2)) and CBDCA (area under the curve = 6) in Japanese patients with advanced NSCLC. Treatment was administered intravenously every 3 weeks initially, followed by some eligible patients receiving maintenance ipilimumab once every 12 weeks. Additional endpoints included safety, tumor response, pharmacokinetics, and immunogenicity.

Results: Fifteen patients were enrolled and 12 received ipilimumab (n = 6, 3 mg/kg; n = 6, 10 mg/kg) in combination with PTX and CBDCA. DLTs occurred in 2 patients (ipilimumab 3 mg/kg) and 1 patient (ipilimumab 10 mg/kg). The most common grade 3/4 adverse events (AEs) were decreased hemoglobin, leukopenia, and neutropenia. The most common immune-related AEs affected the skin, gastrointestinal, and nervous system. The safety profile was similar in both cohorts. Three patients in each cohort achieved a partial response. The pharmacokinetic (PK) profile of ipilimumab in Japanese patients was similar to that observed in previous studies in non-Japanese patients. Conclusions The recommended dose of ipilimumab in phased combination with PTX and CBDCA in Japanese patients with NSCLC was identified as 10 mg/kg. The safety profile was consistent with the previously defined AE profile.

No MeSH data available.


Related in: MedlinePlus

Schema for study CA184-113. C, paclitaxel/carboplatin; DLT, dose-limiting toxicity; IPI, ipilimumab; Tx, treatment; q3wks, every 3 weeks; q12wks, every 12 weeks
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Fig1: Schema for study CA184-113. C, paclitaxel/carboplatin; DLT, dose-limiting toxicity; IPI, ipilimumab; Tx, treatment; q3wks, every 3 weeks; q12wks, every 12 weeks

Mentions: In this open-label, dose-escalation, phase I study, patients with advanced or metastatic NSCLC were treated with ipilimumab (3 or 10 mg/kg) in combination with PTX (175 mg/m2) and CBDCA (area under the curve [AUC] = 6). The treatment schedule was divided into two treatment periods (Fig. 1). During the first treatment period, patients received phased ipilimumab, which consisted of two cycles of PTX/CBDCA every 3 weeks (q3wks) followed by four cycles of ipilimumab plus PTX/CBDCA q3wks. During the second treatment period, patients without disease progression received ipilimumab alone once every 12 weeks (q12wks) as maintenance treatment. To be eligible for maintenance treatment, patients were required to meet core safety criteria and have adequate bone marrow function (ANC > 1500/mm3 and platelet count > 100,000/mm3). Patients were enrolled in successive cohorts of 3 to 6 patients using a standard ‘3 + 3’ design. The recommended dose was defined as the highest dose at which not more than 2 out of 6 patients experienced a dose-limiting toxicity (DLT), taking into consideration the profile of DLTs and the frequency and severity of toxicities after the DLT evaluation period. The final recommended dose was agreed upon by the Sponsor and principal investigator. Patients received ipilimumab at 3 mg/kg (Cohort A) or 10 mg/kg (Cohort B).Fig. 1


Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer.

Horinouchi H, Yamamoto N, Fujiwara Y, Sekine I, Nokihara H, Kubota K, Kanda S, Yagishita S, Wakui H, Kitazono S, Mizugaki H, Tokudome T, Tamura T - Invest New Drugs (2015)

Schema for study CA184-113. C, paclitaxel/carboplatin; DLT, dose-limiting toxicity; IPI, ipilimumab; Tx, treatment; q3wks, every 3 weeks; q12wks, every 12 weeks
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491360&req=5

Fig1: Schema for study CA184-113. C, paclitaxel/carboplatin; DLT, dose-limiting toxicity; IPI, ipilimumab; Tx, treatment; q3wks, every 3 weeks; q12wks, every 12 weeks
Mentions: In this open-label, dose-escalation, phase I study, patients with advanced or metastatic NSCLC were treated with ipilimumab (3 or 10 mg/kg) in combination with PTX (175 mg/m2) and CBDCA (area under the curve [AUC] = 6). The treatment schedule was divided into two treatment periods (Fig. 1). During the first treatment period, patients received phased ipilimumab, which consisted of two cycles of PTX/CBDCA every 3 weeks (q3wks) followed by four cycles of ipilimumab plus PTX/CBDCA q3wks. During the second treatment period, patients without disease progression received ipilimumab alone once every 12 weeks (q12wks) as maintenance treatment. To be eligible for maintenance treatment, patients were required to meet core safety criteria and have adequate bone marrow function (ANC > 1500/mm3 and platelet count > 100,000/mm3). Patients were enrolled in successive cohorts of 3 to 6 patients using a standard ‘3 + 3’ design. The recommended dose was defined as the highest dose at which not more than 2 out of 6 patients experienced a dose-limiting toxicity (DLT), taking into consideration the profile of DLTs and the frequency and severity of toxicities after the DLT evaluation period. The final recommended dose was agreed upon by the Sponsor and principal investigator. Patients received ipilimumab at 3 mg/kg (Cohort A) or 10 mg/kg (Cohort B).Fig. 1

Bottom Line: The most common grade 3/4 adverse events (AEs) were decreased hemoglobin, leukopenia, and neutropenia.The safety profile was similar in both cohorts.The safety profile was consistent with the previously defined AE profile.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan, hhorinou@ncc.go.jp.

ABSTRACT

Background: Ipilimumab is an antibody that targets the cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor response. Adding ipilimumab 10 mg/kg to paclitaxel (PTX) and carboplatin (CBDCA) in a phased schedule improved progression-free survival in a phase II non-small-cell lung cancer (NSCLC) study.

Methods: This dose-escalating, phase I study was designed to identify the recommended dose of ipilimumab (3 or 10 mg/kg) by evaluating dose-limiting toxicity (DLT; Cycles 3 and 4) in phased combination with PTX (175 mg/m(2)) and CBDCA (area under the curve = 6) in Japanese patients with advanced NSCLC. Treatment was administered intravenously every 3 weeks initially, followed by some eligible patients receiving maintenance ipilimumab once every 12 weeks. Additional endpoints included safety, tumor response, pharmacokinetics, and immunogenicity.

Results: Fifteen patients were enrolled and 12 received ipilimumab (n = 6, 3 mg/kg; n = 6, 10 mg/kg) in combination with PTX and CBDCA. DLTs occurred in 2 patients (ipilimumab 3 mg/kg) and 1 patient (ipilimumab 10 mg/kg). The most common grade 3/4 adverse events (AEs) were decreased hemoglobin, leukopenia, and neutropenia. The most common immune-related AEs affected the skin, gastrointestinal, and nervous system. The safety profile was similar in both cohorts. Three patients in each cohort achieved a partial response. The pharmacokinetic (PK) profile of ipilimumab in Japanese patients was similar to that observed in previous studies in non-Japanese patients. Conclusions The recommended dose of ipilimumab in phased combination with PTX and CBDCA in Japanese patients with NSCLC was identified as 10 mg/kg. The safety profile was consistent with the previously defined AE profile.

No MeSH data available.


Related in: MedlinePlus