Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial

65 Background: The aim of this study was to use immunohistochemistry (IHC) to determine the effect of FGFR2 and VEGFR2 expression on treatment outcomes for patients with metastatic or recurrent advanced gastric cancer (AGC) receiving a combination of pazopanib with CapeOx (capecitabine and oxaliplatin). Methods: We conducted a single-arm, open-label phase II study to determine the efficacy and toxicity of the combination of pazopanib with CapeOx in 66 patients with metastatic or recurrent AGC (ClinicalTrials.gov NCT01130805). IHC analysis of FGFR2 and VEGFR2 was possible in 54 patients (81.8%). Results: Among 54 patients, the median age was 51.5 years (range, 23–72 years). Most patients were men (59.3%). Seven patients (13.5%) had tumor tissues that expressed FGFR2 by IHC. No patients had tumors that expressed VEGFR2. Among 7 patients with tumors with FGFR2 expression, 6 achieved partial response (PR) with a 85.7% response rate and one patient with stable disease. Among 47 patients with tumors without FGFR2 expression, one had complete response and 27 had PR (59.5%). A significant difference in PFS was seen between patients who were positive and negative for FGFR2 using IHC (8.5 vs. 5.6 months, p = 0.050). By prognostic analysis for PFS, only FGFR2 status by IHC (positive vs. negative) had significant prognostic value for predicting PFS. Conclusions: FGFR2 expression by IHC might be a useful biomarker for predicting treatment outcomes of patients with metastatic or recurrent AGC treated with a combination of pazopanib and CapeOx.

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An open-label phase II study of lenvatinib plus pembrolizumab in patients with advanced gastric cancer (EPOC1706).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.374 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 374-374 ◽

Cited By ~ 1

Author(s):

Akihito Kawazoe ◽

Shota Fukuoka ◽

Yoshiaki Nakamura ◽

Yasutoshi Kuboki ◽

Yuichi Mikamoto ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Tyrosine Kinases ◽

Objective Response ◽

Progression Free Survival ◽

In Vivo Model ◽

Open Label ◽

Multikinase Inhibitor ◽

Open Label Phase

374 Background: Pembrolizumab, anti–PD-1 antibody, provides response rates of around 15% in patients (pts) with PD-L1-positive advanced gastric cancer (AGC). Lenvatinib, a multikinase inhibitor of VEGF receptors and other receptor tyrosine kinases, substantially decreased the tumor-associated macrophages and increased infiltration of CD8-positive T cells and enhanced anti-tumor activity of PD-1 inhibitors in vivo model. This phase 2 study has been conducted to evaluate efficacy and safety of the combination of lenvatinib plus pembrolizumab in pts with AGC. Methods: Eligible pts were with AGC having measurable lesions according to RECIST ver. 1.1. Pts could be enrolled regardless of PD-L1 status. Pts received 20 mg oral lenvatinib daily plus 200 mg intravenous pembrolizumab every 3 weeks. Primary endpoint was objective response rate (ORR). Planned sample size was 29 pts based on Simon’s optimal two-stage design with one-sided ɑ = 5% and power = 80%. The threshold and expected ORRs were 10% and 30%. PD-L1 combined positive score (CPS) was assessed using the anti–PD-L1 22C3 antibody. Results: From October 2018 to March 2019, 29 pts (27 MSS and 2 MSI-H) were enrolled and assessed for anti-tumor response. Fourteen pts received the study treatment as first-line and 15 pts as second-line. ORR was 69% (95% CI 49 to 85). The disease control rate was 100%. ORR in MSS pts was 70%. ORR was numerically higher in pts with CPS≥1 (n=19, ORR 84%) than that of pts with CPS<1 (n = 10, ORR 40%). Median progression-free survival was 6.9 months (95% CI, 4.4-9.4 months) with 14 pts with ongoing treatment at the data cut off in August 2019. Grade ≥ 3 treatment related adverse events occurred in 13 pts (45%) including hypertension (34%), proteinuria (17%), and platelet count decreased (7%). Conclusions: Lenvatinib with pembrolizumab showed a promising antitumor activity with acceptable safety profiles for pts with AGC, which warrants further investigations in a larger cohort. Clinical trial information: NCT03609359 .

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Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial

The Lancet Oncology ◽

10.1016/s1470-2045(13)70102-5 ◽

2013 ◽

Vol 14 (6) ◽

pp. 490-499 ◽

Cited By ~ 496

Author(s):

Florian Lordick ◽

Yoon-Koo Kang ◽

Hyun-Cheol Chung ◽

Pamela Salman ◽

Sang Cheul Oh ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Open Label ◽

Phase 3 ◽

Open Label Phase

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A phase Ib study of nivolumab plus trastuzumab with S-1/capecitabine plus oxaliplatin for HER2-positive advanced gastric cancer (Ni-HIGH study): Safety evaluation.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4525 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4525-4525

Author(s):

Daisuke Takahari ◽

Hirokazu Shoji ◽

Keiko Minashi ◽

Hiroki Hara ◽

Keisho Chin ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Safety Evaluation ◽

Sensory Neuropathy ◽

Complete Response ◽

Preliminary Evaluation ◽

Her2 Positive ◽

Open Label ◽

Open Label Phase ◽

Grade 3

4525 Background: Addition of an anti-PD-1 antibody to trastuzumab (Tmab) reportedly enhances ADCC activity of Tmab, leading to an additive antitumor effect. We investigated the safety and tolerability of nivolumab (Nivo) plus Tmab combined with S-1 or capecitabine (Cape) and oxaliplatin (Ox) for pts with HER2-positive (+) advanced gastric cancer (AGC). Here, we report the safety evaluation results. Methods: This open-label, phase 1b study was conducted at four centers in Japan. The study consisted of safety (n = 12) and expansion (n = 24–30) parts. Chemotherapy-naïve pts aged ≥ 20 years with histopathologically confirmed HER2+ AGC and measurable lesions were eligible. In the safety evaluation, pts were assigned to cohort 1 or 2 in sequence. Pts received Nivo (360 mg, day 1), Tmab (course 1: 8 mg/kg; course 2–: 6 mg/kg, day 1), Ox (130 mg/m2, day 1) and either S-1 (40 mg/m2 bid, days 1–14; cohort 1) or Cape (1000 mg/m2 bid, days 1–14; cohort 2) every 3 weeks until disease progression or unacceptable toxicity. The primary purpose of the safety evaluation was to determine the toxicity and tolerability of this combination therapy. An independent data and safety monitoring committee assessed the tolerability of the study treatments before starting the second treatment course. A preliminary evaluation of tumor response on the cut-off date (December 16, 2019) was also performed. Results: From November 2018 to August 2019, 12 pts with HER2+ AGC were enrolled in the safety part (six pts each in cohorts 1 and 2). During the 1st course, all 12 pts experienced at least one adverse event (AE). The most common AEs were peripheral sensory neuropathy (PSN) (n = 4) and leukocytopenia (n = 3) in cohort 1 and PSN (n = 5) and anorexia (n = 4) in cohort 2. AEs of grade ≥ 3 were observed in only one pt in cohort 1 (grade 3 neutropenia). No pt suspended or discontinued study treatments due to AEs. One pt in cohort 1 reduced dose of S-1 due to grade 2 erythema and continued the subsequent courses with the dose. After a median follow-up of 6.1 (range, 3.1–13.3) months, one pt from cohort 1 achieved a complete response, eight pts (four in each cohort) achieved a partial response, and three pts (one in cohort 1 and two in cohort 2) showed stable disease. No progressive disease was observed. Conclusions: Both Nivo plus Tmab and either S-1 or Cape plus Ox are tolerable in pts with HER2+ AGC. Both cohorts 1 and 2 have progressed to the expansion part of the study. Clinical trial information: 000034222 .

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